PD-1 deficiency impairs eosinophil recruitment to tissue during Trichinella spiralis infection.

Blockade of programmed cell death 1 (PD-1) is considered a promising strategy for controlling pathogen infection by enhancing host immune cell function. Eosinophils, which play a crucial role in type 2 immune responses, are essential components of the host defense against helminth infection. Here, we investigate the role of PD-1 in eosinophilia during Trichinella spiralis infection in mice. PD-1-deficient (PD-1-/-) mice exhibit delayed expulsion of adult worms and increased muscle larva burdens compared to wild-type mice following infection. Additionally, PD-1-/- mice display impaired recruitment of eosinophils to parasite-invaded tissues, attributed to decreased upregulation of adhesion molecules on both eosinophils and vascular endothelium after infection. The compromised Th2 cytokine response further contributes to impaired adhesion interactions, affecting eosinophil migration and cytotoxicity against larvae in vitro within T. spiralis-infected PD-1-/- mice. Our findings demonstrate a positive role for PD-1 in the recruitment of eosinophils, suggesting its involvement in host defense against helminth infection.

Potent covalent irreversible inhibitor of KRAS G12C IBI351 in patients with advanced solid tumors: First-in-human phase I study.

BACKGROUND: IBI351 is an irreversible and covalent inhibitor of KRAS G12C. Despite FDA approval of two KRAS G12C inhibitors, there are still significant unmet clinical needs in Chinese patients and ongoing concerns about the optimal dosage. Herein, we presented the phase Ia/Ib study of IBI351 monotherapy in Chinese patients with advanced solid tumors harboring KRAS G12C mutation. METHODS: In phase Ia dose escalation, IBI351 at 250/450/700/900 mg once daily and 450/600/750 mg twice daily (BID) were evaluated. Potentially efficacious doses and optimal recommended phase 2 dose (RP2D) were further evaluated in patients with advanced non-small cell lung cancer (NSCLC) in phase Ia dose expansion and phase Ib. Safety, pharmacokinetics, and investigator-assessed tumor response were evaluated. RESULTS: As of June 13, 2023, 176 patients were enrolled. IBI351 was well tolerated with no dose-limiting toxicity reported across all evaluated doses. The RP2D was determined as 600 mg BID by considering safety, efficacy and pharmacokinetics. A total of 168 patients (95.5 %) had at least one treatment-related adverse event (TRAE), and 64 patients (36.4 %) had grade 3 or higher TRAEs, most commonly gamma-glutamyl transferase increased (10.2 %) and anemia (6.8 %). For patients with NSCLC, the confirmed objective response rate (ORR) was 45.5 % across all doses. At 600 mg BID, the confirmed ORR was 46.8 % and median progression-free survival was 9.6 months with a median follow-up of 6.9 months. CONCLUSIONS: IBI351 was well tolerated in patients with advanced solid tumors and showed promising antitumor activity in advanced NSCLC patients with KRAS G12C mutation.

Summary of Best Evidence for Perioperative Management Practices in Hair Transplantation Patients : Facial Skeleton.

AIM: To integrate and summarize the best evidence on perioperative management practices for hair transplantation patients, providing an evidence-based reference for clinical. METHODS: An exhaustive literature search was conducted to identify the best evidence for managing patients undergoing hair transplantation during the perioperative period. The databases searched included Up To Date, BMJ Best Practice, UK National Institute for Health and Care Excellence, National Guideline Clearing House, Scottish Intercollegiate Guidelines Network, Guidelines International Network, Cochrane Library, JBI Database of Systematic Reviews and Implementation Reports, PubMed, Web of Science, European Dermatology Forum, China National Knowledge Infrastructure, Wanfang Data, Medlive Guideline Network, and Sinomed. The search spanned publications from February 2013 to February 2024, focusing on clinical decisions, evidence summaries, guidelines, and expert consensus. RESULTS: We finally identified 22 articles with high-quality results (consisting of 9 clinical decisions, 6 guidelines, 7 expert consensuses), providing 41 pieces of evidence across seven categories: assessment of transplantation conditions, transplant planning and preoperative preparation, anesthetic preparations, surgical methods and operation skills, postoperative wound management, medication-related guidance, optimization of nursing and treatment strategies. Special emphasis has been placed on the sections covering anesthesia preparation, surgical methods, and operational techniques, with detailed explanations provided. CONCLUSION: The summarized best evidence on perioperative management practices for hair transplantation patients can serve as evidence-based guidelines for clinical. It is recommended that clinical staff adopt evidence-based recommendations to improve and optimize patient outcomes and promote postoperative recovery. As these evidences came from different countries, factors such as the clinical environment should be evaluated before application. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Melittin treatment suppressed malignant NSCLC progression through enhancing CTSB-mediated hyperautophagy.

Melittin is preclinically investigated as anticancer agent in multiple tumor types. But its regulation role and regulatory mechanism regarding NSCLC is unknown. In our investigation, Proteomic test was employed to identify proteins that expressed abnormally in cancer cells and that with Melittin treatmented. The results showed CTSB was one of the Top proteins with different expression levels in the lysosomes of Melittin-treatmented cancer cells and showed an up-regulation trend. CTSB expression was increased in NSCLC cancer tissues compared to adjacent normal tissues, as demonstrated in lung cancer tissue chips experiment. However, Melittin treatment increased the CTSB level in lysosomes, which inhibited the malignant progression of NSCLC. We hypothesized that the relative homeostasis of CTSB in cancer cells was destroyed, and CTSB exerts its hydrolytic effect excessively, resulting in excessive autophagy of cancer cells, thus inhibiting the malignant progression of cancer cells. The direct combination of Melittin and CTSB was proposed by molecular docking technique, LiP-SMap was used to analyze the target genes and active components extracted from high-throughput sequencing proteomic data, and successfully verified that melittin was successfully demonstrated to directly target CTSB-binding. In vivo and in vitro studies have shown that Melittin treatment inhibits the malignant progression of A549 and HCC1833 cells and animal tumors, namely non-small cell lung cancer, by promoting CTSB-mediated hyperautophagy. CTSB-specific inhibitor CA-074 Me and autophagy inhibitor 3-MA treatment reversed the inhibit effect of Melittin to the malignant progression of NSCLC. Taken together, Melittin treatment inhibited malignant progression regarding NSCLC through enhancing CTSB-mediated hyperautophagy.

Population pharmacokinetics and dosing simulations of meropenem in septic critically ill patients with complicated intra-abdominal infection or pneumonia.

OBJECTIVES: Meropenem pharmacokinetics (PK) may be altered in septic critically ill patients with complicated intra-abdominal infections (cIAI) and pneumonia. We aimed to evaluate the covariates affecting meropenem PK and the performance of different dosing regimens to optimize the PK/pharmacodynamic target. METHODS: Population PK analysis was performed using non-linear mixed-effects modeling. The final model was validated and used to simulate meropenem exposure to assess the probability of attaining the 100%ƒT>MIC target. RESULTS: Forty-six and 14 patients were respectively enrolled for PK analysis and external validation. A one-compartment linear model adequately described the data of 226 concentrations. The typical clearance (CL) and volume of distribution (Vd) were 9.69 L/h and 27.4 L, respectively. Septic shock from cIAI (cIASS) and actual body weight were significant covariates for meropenem Vd in addition to the influential covariates of creatinine clearance (CLCR-CG) and augmented renal clearance for CL. External validation showed the robustness and accuracy of this model. Simulation results proposed continuous infusion (CI) dosing regimens of meropenem against pathogens with MICs ≥ 2 mg/L in patients with cIASS and CLCR-CG ≥ 60 mL/min. CONCLUSIONS: For the patients with cIASS and CLCR-CG ≥ 60 mL/min, CI meropenem is proposed for treatment of less sensitive pathogens with MICs ≥ 2 mg/L.

Effect of refrigeration and reheating on the lipid oxidation and volatile compounds in silver carp surimi gels.

BACKGROUND: As unsaturated and saturated aldehydes, ketones are known to be responsible for off-odors in surimi products, and they are mainly derived from lipid oxidation. Because surimi-based products are rich in unsaturated fatty acids, they are prone to producing off-odors during the refrigeration and reheating processes, which are common treatments for leftovers. The present study investigated the color, lipid oxidation productions, fatty acid profiles and volatile components in surimi gels during refrigeration at 4 °C for 3 days with multiple reheating. RESULTS: The results revealed that the accumulation rate of hydroperoxides was higher in the refrigeration stage, whereas the decomposition rate was higher during reheating in surimi gels. Both refrigeration and reheating treatments promoted conjugated diene values, acid values and carbonyl values. Nevertheless, reheating treatment decreased tohiobarbituric acid reactive substances and whiteness. The contents of unsaturated fatty acids, especially α-linolenic acid, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, were reduced, whereas the contents of saturated fatty acids increased during refrigeration and multiple reheating. The unsaturated fatty acids were lost as a result of their oxidative deterioration. The volatile components profile showed that the accumulation of volatile components mainly occurred in the refrigeration stage. Multivariate data analysis was utilized to further clarify whether the off-odors in surimi gels were mainly generated in refrigeration. CONCLUSION: Refrigeration and reheating both contributed to lipid oxidation and the generation of volatile compounds in surimi gels, but the off-odors were mainly generated during refrigeration. This research provides a novel understanding of the formation of food odors in processing. © 2024 Society of Chemical Industry.

Application value of P-selectin and Clara cell secretory protein 16 expression in children with severe adenovirus pneumonia.

This study investigated the roles of P-selectin and Clara cell secretory protein 16 (CC16) levels in the pathogenesis of severe adenovirus (ADV) pneumonia in children and evaluated their ability to predict disease. Fifty-one children (age, 1-5 years) with ADV pneumonia who were admitted to Xiamen Children's Hospital were included in this study and divided into the mild group (24 patients) and severe group (27 patients). A control group comprising healthy children of the same age who underwent routine physical examinations during the same period (30 patients) was also included. The univariate analysis demonstrated that the levels of the white blood cell count and C-reactive protein, procalcitonin, d-dimer, and P-selectin were increased in a severe group compared with a mild group, while CC16 levels were significantly decreased (p < 0.05). The logistic regression analysis revealed that P-selectin and CC16 levels were independent risk factors for severe ADV pneumonia in children. The areas under the ROC curves suggested that P-selectin and CC16 exhibited high predictive value for severe ADV pneumonia. P-selectin values more than 898.58 pg/mL and CC16 values less than 11.355 ng/mL predicted severe ADV pneumonia. P-selectin and CC16 levels are correlated with the severity of ADV pneumonia in children.

Top-down mass spectrometry analysis of capsid proteins of recombinant adeno-associated virus using multiple ion activations and proton transfer charge reduction.

Adeno-associated viruses (AAVs) are common vectors for emerging gene therapies due to their lack of pathogenicity in humans. Here, we present our investigation of the viral proteins (i.e., VP1, VP2, and VP3) of the capsid of AAVs via top-down mass spectrometry (MS). These proteins, ranging from 59 to 81 kDa, were chromatographically separated using hydrophilic interaction liquid chromatography and characterized in the gas-phase by high-resolution Orbitrap Fourier transform MS. Complementary ion dissociation methods were utilized to improve the overall sequence coverage. By reducing the overlap of product ion signals via proton transfer charge reduction on the Orbitrap Ascend BioPharma Tribrid mass spectrometer, the sequence coverage of each VP was significantly increased, reaching up to ∼40% in the case of VP3. These results showcase the improvements in the sequencing of proteins >30 kDa that can be achieved by manipulating product ions via gas-phase reactions to obtain easy-to-interpret fragmentation mass spectra.

Gold-Catalyzed Alkyne Oxidative Cyclization/Mannich-Type Addition Cascade Reaction of Ynamides with 1,3,5-Triazinanes.

Herein, a gold-catalyzed alkyne oxidative cyclization/Mannich-type addition cascade reaction of ynamides with 1,3,5-triazinanes in the presence of a Brønsted acid has been presented. A class of functionalized fluorenes bearing a quaternary carbon center was synthesized directly with moderate to excellent yields via in situ formed α-oxo carbenes using quinoline N-oxide as the oxidant under mild reaction conditions.

Towards a universal method for middle-down analysis of antibodies via proton transfer charge reduction-Orbitrap mass spectrometry.

Modern mass spectrometry technology allows for extensive sequencing of the ~ 25 kDa subunits of monoclonal antibodies (mAbs) produced by IdeS proteolysis followed by disulfide bond reduction, an approach known as middle-down mass spectrometry (MD MS). However, the spectral congestion of tandem mass spectra of large polypeptides dramatically complicates fragment ion assignment. Here, we report the development and benchmark of an MD MS strategy based on the combination of different ion fragmentation techniques with proton transfer charge reduction (PTCR) to simplify the gas-phase sequencing of mAb subunits. Applied on the liquid chromatography time scale using an Orbitrap Tribrid mass spectrometer, PTCR produces easy-to-interpret mass spectra with limited ion signal overlap. We demonstrate that the accurate estimation of the number of charges submitted to the Orbitrap mass analyzer after PTCR allows for the detection of charge-reduced product ions over a wide mass-over-charge (m/z) window with low parts per million m/z accuracy. Therefore, PTCR-based MD MS analysis increases not only sequence coverage, number of uniquely identified fragments, and number of assigned complementary ion pairs, but also the general confidence in the assignment of subunit fragments. This data acquisition method can be readily applied to any class of mAbs without an apparent need for optimization, and benefits from the high resolving power of the Orbitrap mass analyzer to return sequence coverage of individual subunits exceeding 80% in a single run, and > 90% when just two experiments are combined.

Peripheral-Type Facial Paralysis and Unilateral Hemisphere Hemorrhage.

This case report describes a patient in his 60s with peripheral-type paralysis and hemorrhage in the left thalamus-radiation crown region.

The efficacy and safety of continuous theta burst stimulation for auditory hallucinations: a systematic review and meta-analysis of randomized controlled trials.

Objective: Auditory hallucinations are the most frequently occurring psychotic symptom in schizophrenia. Continuous theta burst stimulation (cTBS) has been used as an adjuvant treatment for auditory hallucinations. This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia. Methods: We performed a comprehensive search of four international databases from their inception to January 14, 2024, to identify relevant RCTs that assessed the effects of adjuvant cTBS on auditory hallucinations. The key words included "auditory hallucinations", "continuous theta burst stimulation" and "transcranial magnetic stimulation". Inclusion criteria included patients with auditory hallucinations in schizophrenia or schizoaffective disorder. The Revised Cochrane risk-of-bias tool for randomized trials (RoB1) were used to evaluate the risk of bias and the Review Manager Software Version 5.4 was employed to pool the data. Results: A total of 4 RCTs involving 151 patients with auditory hallucinations were included in the analysis. The Cochrane risk of bias of these studies presented "low risk" in all items. Preliminary analysis showed no significant advantage of adjuvant cTBS over sham stimulation in reducing hallucinations [4 RCTs, n = 151; SMD: -0.45 (95%CI: -1.01, 0.12), P = 0.13; I2 = 61%]. Subgroup analysis revealed that patients treated with adjuvant cTBS for more than 10 stimulation sessions and total number of pulses more than 6000 [3 RCTs, n = 87; SMD: -4.43 (95%CI: -8.22, -0.63), P = 0.02; I2 = 47%] had a statistically significant improvement in hallucination symptoms. Moreover, the rates of adverse events and discontinuation did not show any significant difference between the cTBS and sham group. Conclusions: Although preliminary analysis did not revealed a significant advantage of adjuvant cTBS over sham stimulation, subgroup analysis showed that specific parameters of cTBS appear to be effective in the treatment of auditory hallucinations in schizophrenia. Further large-scale studies are needed to determine the standard protocol of cTBS for treating auditory hallucinations. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024534045.

Deep representation learning from electronic medical records identifies distinct symptom based subtypes and progression patterns for COVID-19 prognosis.

OBJECTIVE: Symptoms are significant kind of phenotypes for managing and controlling of the burst of acute infectious diseases, such as COVID-19. Although patterns of symptom clusters and time series have been considered the high potential prediction factors for the prognosis of patients, the elaborated subtypes and their progression patterns based on symptom phenotypes related to the prognosis of COVID-19 patients still need be detected. This study aims to investigate patient subtypes and their progression patterns with distinct features of outcome and prognosis. METHODS: This study included a total of 14,139 longitudinal electronic medical records (EMRs) obtained from four hospitals in Hubei Province, China, involving 2,683 individuals in the early stage of COVID-19 pandemic. A deep representation learning model was developed to help acquire the symptom profiles of patients. K-means clustering algorithm is used to divide them into distinct subtypes. Subsequently, symptom progression patterns were identified by considering the subtypes associated with patients upon admission and discharge. Furthermore, we used Fisher's test to identify significant clinical entities for each subtype. RESULTS: Three distinct patient subtypes exhibiting specific symptoms and prognosis have been identified. Particularly, Subtype 0 includes 44.2% of the whole and is characterized by poor appetite, fatigue and sleep disorders; Subtype 1 includes 25.6% cases and is characterized by confusion, cough with bloody sputum, encopresis and urinary incontinence; Subtype 2 includes 30.2% cases and is characterized by dry cough and rhinorrhea. These three subtypes demonstrate significant disparities in prognosis, with the mortality rates of 4.72%, 8.59%, and 0.25% respectively. Furthermore, symptom cluster progression patterns showed that patients with Subtype 0 who manifest dark yellow urine, chest pain, etc. in the admission stage exhibit an elevated risk of transforming into the more severe subtypes with poor outcome, whereas those presenting with nausea and vomiting tend to incline towards entering the milder subtype. CONCLUSION: This study has proposed a clinical meaningful approach by utilizing the deep representation learning and real-world EMR data containing symptom phenotypes to identify the COVID-19 subtypes and their progression patterns. The results would be potentially useful to help improve the precise stratification and management of acute infectious diseases.

Remote sensing estimates of global sea surface nitrate: Methodology and validation.

Information about sea surface nitrate (SSN) concentrations is crucial for estimating oceanic new productivity and for carbon cycle studies. Due to the absence of optical properties in SSN and the intricate relationships with environmental factors affecting spatiotemporal dynamics, developing a more representative and widely applicable remote sensing inversion algorithm for SSN is challenging. Most methods for the remote estimation of SSN are based on data-driven neural networks or deep learning and lack mechanistic descriptions. Since fitting functions between the SSN and sea surface temperature (SST), mixed layer depth (MLD), and chlorophyll (Chl) content have been established for the open ocean, it is important to include the remote sensing indicator photosynthetically active radiation (PAR), which is critical in nitrate biogeochemical processes. In this study, we employed an algorithm for estimating the monthly average SSN on a global 1° by 1° resolution grid; this algorithm relies on the empirical relationship between the World Ocean Atlas 2018 (WOA18) monthly interpolated climatology of nitrate in each 1° × 1° grid and the estimated monthly SST and PAR datasets from Moderate Resolution Imaging Spectroradiometer (MODIS) and MLD from the Hybrid Coordinate Ocean Model (HYCOM). These results indicated that PAR potentially affects SSN. Furthermore, validation of the SSN model with measured nitrate data from different months and locations for the years 2018-2023 yielded a high prediction accuracy (N = 12,846, R2 = 0.93, root mean square difference (RMSE) = 3.12 µmol/L, and mean absolute error (MAE) = 2.22 µmol/L). Further independent validation and sensitivity tests demonstrated the validity of the algorithm for retrieving SSN.

The role of immune cells and immune related genes in the tumor microenvironment of papillary thyroid cancer and their significance for immunotherapy.

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer (THCA) and shows a better prognosis than other types. However, further research is needed to determine the risk of PTC. We herein used the CIBERSORT algorithm to analyze the gene-expression profile obtained from TCGA, estimated the infiltration ratio of 22 immune cell types in tumor tissues and normal tissues, analyzed the differential expression of immune-related genes, and identified immune cells and immune-related genes related to clinical progress and prognosis. We uncovered 12 immune cell types and nine immune-related genes that were closely correlated with TNM staging, and two immune cell types (activated NK cells and γδT cells) and one immune-related gene (CD40LG) that were associated with prognosis. After evaluation, four immune cell types could be used to determine low-risk PTC, with six immune cell types and six immune-related genes closely associated with high-risk PTC. The type and quantity of infiltrating immune cells in the microenvironment of PTC, as well as immune-related genes, appear to be closely related to tumor progression and can therefore be used as important indicators for the evaluation of patient prognosis. We posit that the study of immune cells and immune-related genes in the tumor microenvironment will facilitate the determination of low-risk PTC more accurately, and that this will greatly promote the development of high-risk PTC immunotherapy.

Efficacy and Safety of KRASG12C Inhibitor IBI351 Monotherapy in Patients With Advanced NSCLC: Results From a Phase 2 Pivotal Study.

INTRODUCTION: KRAS glycine-to-cysteine substitution at codon 12 (G12C) mutation is a well-recognized and increasingly promising therapeutic target with huge unmet clinical needs in NSCLC patients. IBI351 is a potent covalent and irreversible inhibitor of KRAS G12C. Here, we present the efficacy and safety of IBI351 from an open-label, single-arm, phase 2 pivotal study. METHODS: Eligible patients with NSCLC with KRAS G12C who failed standard therapy were enrolled. IBI351 was orally administered at a dose of 600 mg twice daily. The primary endpoint was confirmed objective response rate assessed by an independent radiological review committee (IRRC) as per Response Evaluation Criteria in Solid Tumors v1.1. Other endpoints were safety, IRRC-confirmed disease control rate, duration of response, progression-free survival (PFS), and overall survival. RESULTS: As of December 13, 2023, 116 patients were enrolled (Eastern Cooperative Oncology Group Performance Status 1: 91.4%; brain metastasis: 30.2%; prior treatments with both anti-PD-1 or anti-PD-L1 inhibitors and platinum-based chemotherapy: 84.5%). As per the IRRC assessment, the confirmed objective response rate was 49.1% (95% confidence interval [CI]: 39.7-58.6), and the disease control rate was 90.5% (95% CI: 83.7-95.2). The median duration of response was not reached whereas disease progression or death events occurred in 22 patients (38.6%), and the median PFS was 9.7 months (95% CI: 5.6-11.0). overall survival data was immature. Treatment-related adverse events (TRAEs) occurred in 107 patients (92.2%) whereas 48 patients (41.4%) had equal to or higher than grade three TRAEs. Common TRAEs were anemia (44.8%), increased alanine aminotransferase (28.4%), increased aspartate aminotransferase (27.6%), asthenia (26.7%) and presence of protein in urine (25.0%). TRAEs leading to treatment discontinuation occurred in nine patients (7.8%). In biomarker evaluable patients (n = 95), all patients had positive KRAS G12C in tissue whereas 72 patients were blood-positive and 23 were blood-negative for KRAS G12C. Patients with KRAS G12C in both blood and tissue had higher tumor burden at baseline (p < 0.05) and worse PFS (p < 0.05). Tumor mutation profiling identified tumor protein p53 (45.3%), serine/threonine kinase 11 (STK11) (30.5%), and kelch-like ECH-associated protein 1 (21.1%) as the most common genes co-mutated with KRAS G12C. Among 13 genes with mutation frequency equal to or higher than 5%, mutations of six genes (STK11, kelch-like ECH-associated protein 1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma, DNA polymerase epsilon, SMAD family member 4, and BMP/retinoic acid-inducible neural-specific protein 3) were significantly associated with worse PFS (p < 0.05). Mutation in STK11 was also found to have a significant association with higher tumor burden at baseline and lower response rate (p < 0.05). CONCLUSIONS: IBI351 monotherapy demonstrated promising and sustained efficacy with manageable safety, supporting its potential as a new treatment option for KRAS G12C-mutant NSCLC.

Covalent-Organic Frameworks for Selective and Sensitive Detection of Antibiotics from Water.

As the consumption of antibiotics rises, they have generated some negative impacts on organisms and the environment because they are often unable to be effectively degraded, and seeking effective detection methods is currently a challenge. Covalent-organic frameworks (COFs) are new types of crystalline porous crystals created based on the strong covalent interactions between blocked monomers, and COFs demonstrate great potential in the detection of antibiotics from aqueous solutions because of their large surface area, adjustable porosity, recyclability, and predictable structure. This review aims to present state-of-the-art insights into COFs (properties, classification, synthesis methods, and functionalization). The key mechanisms for the detection of antibiotics and the application performance of COFs in the detection of antibiotics from water are also discussed, followed by the challenges and opportunities for COFs in future research.

Short-term effect of low-dose roxadustat combined with erythropoiesis-stimulating agent treatment for erythropoietin-resistant anemia in patients undergoing maintenance hemodialysis.

Background: Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week). Methods: The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO. Results: The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased. Conclusion: Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism.

Case report: dose-dependent interaction between dexamethasone and voriconazole in severely ill patients with non-Hodgkin's lymphoma being treated for invasive pulmonary aspergillosis.

Background: Voriconazole is primarily metabolized by CYP2C19 and CYP3A4. Drug interactions that affect this pathway can alter its plasma exposures, resulting in untargeted voriconazole concentrations. Case summary: In this case report, we describe the case of a 64-year-old man who was treated for non-Hodgkin's lymphoma with continuous glucocorticoids co-administrated with voriconazole against invasive pulmonary aspergillosis. A decrease in trough concentration (Cmin) of voriconazole was observed and related with co-administration of dexamethasone in the patient carrying the CYP2C19 *1*2 genotype: voriconazole Cmin/dose ratios of 0.018 (0.1 mg L-1/5.7 mg kg-1 day-1), 0.18 (1 mg L-1/5.7 mg kg-1 day-1), and 0.23 (2 mg L-1/8.6 mg kg-1 day-1) at dexamethasone doses of 20, 12.5, and 2.5 mg, respectively. Sub-therapeutic voriconazole Cmin was associated with high- and moderate-dose dexamethasone (20 and 12.5 mg), leading to failure of antifungal treatment. Conclusion: The extent of voriconazole-dexamethasone interaction was determined by the dose of dexamethasone and associated with the CYP2C19 *1*2 genotype. Therapeutic drug monitoring of voriconazole is necessary to avoid clinically relevant interactions for optimal antifungal therapy.