Cost-effectiveness analysis of tislelizumab plus chemotherapy as the first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma in China.

OBJECTIVE: We aimed to investigate the cost-effectiveness of tislelizumab plus chemotherapy compared to chemotherapy alone as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (OSCC). METHODS: A partitioned survival model was developed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic OSCC over a 10-year lifetime horizon from the perspective of the Chinese healthcare system. Costs and utilities were derived from the drug procurement platform and published literature. The model outcomes comprised of costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were conducted to address uncertainty and ensure the robustness of the model. RESULTS: Tislelizumab plus chemotherapy yielded an additional 0.337 QALYs and incremental costs of $7,117.007 compared with placebo plus chemotherapy, generating an ICER of $21,116.75 per QALY, which was between 1 time ($12,674.89/QALY) and 3 times GDP ($38,024.67/QALY) per capita. In one-way sensitivity analysis, the ICER is most affected by the cost of oxaliplatin, paclitaxel and tislelizumab. In the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set as 1 or 3 times GDP per capita, the probability of tislelizumab plus chemotherapy being cost-effective was 1% and 100%, respectively. CONCLUSION: Tislelizumab plus chemotherapy was probably cost-effective compared with chemotherapy alone as the first-line treatment for advanced or metastatic OSCC in China.

Evaluation of omadacycline regimens for community-acquired bacterial pneumonia patients infected with Staphylococcus Aureus by pharmacokinetic/pharmacodynamic analysis.

Omadacycline is an FDA-approved agent for community-acquired bacterial pneumonia (CABP). The purpose of this study is to evaluate the effectiveness of omadacycline for treating CABP patients infected with Staphylococcus aureus, including Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin-Susceptible Staphylococcus aureus (MSSA), using pharmacokinetic/pharmacodynamic (PK/PD) analysis. Monte Carlo simulations (MCSs) were performed by utilizing omadacycline pharmacokinetic (PK) parameters, minimum inhibitory concentration (MIC) data, and in vivo PK/PD targets to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) values for different dose regimens against MRSA and MSSA in CABP patients. A dosage regimen with a PTA or CFR expectation value greater than 90% was considered optimal. For all recommended dose regimens, PTA values for MRSA MIC ≤1 and MSSA MIC ≤4 on days 1, 4, and 7 were greater than 90%. Based on the MIC distribution of Staphylococcus aureus, all dose regimens had CFR values greater than 90% for both MRSA and MSSA. CFR values for different bacterial strains were still greater than 90% within the range of PK/PD target values less than 40, although they gradually decreased with increasing PK/PD target values. PK/PD modeling demonstrated that all recommended dose regimens of omadacycline are highly effective against CABP patients infected with MRSA and MSSA. The study provides theoretical support for the efficacy of omadacycline in different dose regimens.

Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism.

BACKGROUND: Liver fibrosis is a formidable global medical challenge, with no effective clinical treatment currently available. Yinhuang granule (YHG) is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos. It is frequently used for upper respiratory tract infections, pharyngitis, as well as acute and chronic tonsillitis. AIM: To investigate the potential of YHG in alleviating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. METHODS: To induce a hepatic fibrosis model in mice, this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk. Meanwhile, liver fibrosis mice in the low dose of YHG (0.4 g/kg) and high dose of YHG (0.8 g/kg) groups were orally administered YHG once a day for 4 wk. Serum alanine/aspartate aminotransferase (ALT/AST) activity and liver hydroxyproline content were detected. Sirius red and Masson's trichrome staining assay were conducted. Real-time polymerase chain reaction, western-blot and enzyme-linked immunosorbent assay were conducted. Liver glutathione content, superoxide dismutase activity level, reactive oxygen species and protein carbonylation amount were detected. RESULTS: The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice, as reflected by decreased serum ALT/AST activity and improved liver histological evaluation. YHG also attenuated liver fibrosis, evident through reduced liver hydroxyproline content, improvements in Sirius red and Masson's trichrome staining, and lowered serum hyaluronic acid levels. Furthermore, YHG hindered the activation of hepatic stellate cells (HSCs) and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice. YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-dependent downstream antioxidant genes. In addition, YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice, as demonstrated by increased liver adenosine triphosphate content, mitochondrial DNA levels, and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1. CONCLUSION: YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs, reducing inflammation, alleviating liver oxidative stress damage through Nrf2 activation, and promoting liver mitochondrial biogenesis.

Numerical analyses for three-dimensional face stability of circular tunnels in purely cohesive soils with linearly increasing strength.

The tunnel face stability in purely cohesive soils with linearly increasing strength was investigated using three-dimensional finite element limit analysis (FELA). Both the collapse (active failure) and blow-out (passive failure) of the tunnel face were considered in the analysis. The rigorous upper bound (UB) and lower bound (LB) solutions of the load factor were calculated with a wide range of ground conditions to cover a broad scope of practical application. The results showed that the whole surface of the face is at failure in the collapse case; while in the blow-out case, there exists a gradual evolution process from partial failure to global failure within the tunnel face with increasing buried depth. Later, based on 960 finite element limit analysis results, a series of practical equations were proposed for tunnel face stability analysis in purely cohesive soils. These equations can be employed to quickly calculate the UB and LB solutions of the limit support pressure and the stability number of a tunnel face in both the collapse and blow-out cases. Finally, the calculation results from these equations were compared with those from previous studies in detail. The comparisons showed that the proposed equations make an improvement over existing methods and can be used as an efficient tool in practical engineering.

Exploring the effect of Wuzhi capsule on the pharmacokinetics of regorafenib and its main metabolites in rat plasma using liquid chromatography-tandem mass spectrometry.

Regorafenib is a small-molecule tyrosine kinase inhibitor with severe hepatotoxicity. It undergoes metabolism mainly by CYP3A4 to generate active metabolites regorafenib-N-oxide (M2) and N-desmethyl-regorafenib-N-oxide (M5). Wuzhi capsule (WZC) is an herbal preparation derived from Schisandra sphenanthera and is potentially used to prevent regorafenib-induced hepatotoxicity. This study aims to explore the effect of WZC on the pharmacokinetics of regorafenib in rats. An efficient and sensitive liquid chromatography-tandem mass spectrometry method was developed to quantitatively determine regorafenib and its main metabolites in rat plasma. The proposed method was applied to the pharmacokinetic study of regorafenib in rats, with or without WZC. Coadministration of regorafenib with WZC resulted in a prolonged mean residence time (MRT) of the parent drug but had no statistically significant difference in other pharmacokinetic parameters. While for the main metabolites of regorafenib, WZC decreased the area under the curve and maximum concentration (Cmax ), delayed the time to reach Cmax , and prolonged the MRT of M2 and M5. These results indicate that WZC delayed and inhibited the metabolism of regorafenib to M2 and M5 by suppressing CYP3A4. Our study provides implications for the rational use of the WZC-regorafenib combination in clinical practice.

Application of hip capsule peripheral nerve block in early analgesia in elderly patients with hip fracture.

Objective: The objective of the study is to investigate the effect of pericapsular nerve group (PENG) block in early analgesia in elderly patients with hip fracture. Methods: A total of 44 elderly patients with hip fracture admitted to our hospital from August 2021 to December 2022 were selected and divided into 2 groups according to different analgesia programs. Results: At T1~T4, the resting and active visual analog scale (VAS) scores in group P were lower than group F (p < 0.05). The resting and active VAS scores at T5 in both groups were no visible differences (p > 0.05). After 30 min of block, systolic blood pressure, diastolic blood pressure, and heart rate were decreased in both groups (p < 0.05), but no obvious difference was found in the two groups (p > 0.05). Before surgery, Pittsburgh Sleep Quality Index (PSQI) and mini-mental state scale (MMSE) scores in both groups were reduced, and PSQI score in group P was lower than that in group F and MMSE score was higher than group F (p < 0.05). Conclusion: PENG technology is safe and effective in the early analgesia of elderly hip fractures. It can effectively block physiological stress response caused by acute trauma, improve pre-operative sleep quality, and reduce the incidence of cognitive dysfunction.

Objetivo: Investigar el efecto del bloqueo del grupo del nervio pericapsular en analgesia temprana en pacientes ancianos con fractura de cadera. Método: Se seleccionaron 44 pacientes ancianos con fractura de cadera ingresados en nuestro hospital entre agosto de 2021 y diciembre de 2022, divididos en dos grupos según diferentes programas de analgesia. Resultados: En T1~T4, los valores de la escala visual análoga (EVA) en reposo y con actividad en el grupo P fueron menores que en el grupo F (p < 0.05). Los puntajes de la EVA en reposo y en actividad en T5 en ambos grupos no mostraron diferencias visibles (p > 0.05). Después de 30 minutos de bloqueo, la presión arterial sistólica y diastólica, y la frecuencia cardiaca, disminuyeron en ambos grupos (p < 0.05), pero no se encontró una diferencia obvia entre ellos (p > 0.05). Antes de la cirugía, las puntuaciones del Pittsburgh Sleep Quality Index (PSQI) y de la Mini-Mental State Scale (MMSE) en ambos grupos eran reducidas, y la puntuación del PSQI en el grupo P fue menor que en el grupo F, y la puntuación del MMSE fue mayor que en el grupo F (p < 0.05). Conclusiones: La técnica de bloqueo del grupo del nervio pericapsular es segura y efectiva en la analgesia temprana de fracturas de cadera en ancianos. Puede bloquear eficazmente la respuesta al estrés fisiológico causado por un trauma agudo, mejorar la calidad del sueño preoperatorio y reducir la incidencia de disfunción cognitiva.

Retraction: Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils.

Retraction of 'Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils' by Tao Li et al., Biomater. Sci., 2021, 9, 2931-2946, https://doi.org/10.1039/D0BM02126A.

Sustaining Heteronormativity in Marriage: How Chinese Newspapers Frame Heterosexual Marriage Undertaken by Chinese Queer People.

Family members often cite broader societal discourses and norms when forcing Chinese queer people to engage in heterosexual marriage (referred to as HMQ; heterosexual marriage undertaken by Chinese queer people). It is unclear what these social norms entail and how the norms are maintained. This paper examines 89 Chinese newspaper articles to uncover the societal discourses driving families to pressure queer people into heterosexual marriage. We identified three framings: (1) Highlighting problems of formality marriage (the marriage between two queer people) and gay's wife marriage (the marriage between a queer man and a heterosexual woman); (2) portraying people involved in formality marriage and gay's wife marriage as suffering from heteronormative pressure to engage in marriage; and (3) presenting formality marriage in a collaboration frame and gay's wife marriage in a deception frame. These framings suggest heteronormativity in marriage is upheld in societal discourses about HMQ and sustained by two hierarchies created in Chinese newspaper articles: one degrading queer marriage practices, which made heterosexual marriage undertaken by queer people inferior to ideal heterosexual marriage; another stratifying queer marriage practices, which made the marriage between a queer man and a heterosexual woman less acceptable than the marriage between two queer people.

11B NMR of the Morphological Evolution of Traditional Chinese Medicine Borax.

This article applies nuclear magnetic resonance technology to the study of boron-containing traditional Chinese medicine, in order to explore the morphological evolution of boron elements in traditional Chinese medicine. Borax is a traditional Chinese medicine with anti-corrosion, anti-inflammatory, antibacterial, and anticonvulsant effects. It is made by boiling, removing stones, and drying borax minerals like borate salts. This article introduces an 11B nuclear magnetic resonance method for identifying and characterizing boron-containing compounds in TCM. We applied this technology to borax aqueous solutions in different chemical environments and found that with boron mixed in the form of SP2 hybridization in equilateral triangles and SP3 hybridization in equilateral tetrahedra, the pH changes in alkaline environments significantly affected the ratio of the two. At the same time, it was found that in addition to the raw material peak, boron signals of other boron-containing compounds were also detected in 20 commercially available boron-containing TCM preparations. These new boron-containing compounds may be true pharmaceutical active ingredients, and adding them directly to the formula can improve quality and safety. This article describes the detection of 11B NMR in boron-containing traditional Chinese medicine preparations. It is simple, non-destructive, and can provide chemical fingerprint studies for boron-containing traditional Chinese medicine.

Catalytic degradation of rhodamine B by titanium dioxide doped polydopamine photoresponsive composites.

Titanium dioxide-based materials treat wastewater contaminated by organic pollutants. However, the wide band gap and the ease of agglomeration limit its photocatalytic activity. PDA/PEI@TiO2@P-HSM composites were synthesized using PDA/PEI as an interfacial bonding modifier via polymerization reaction. Phase and chemical bonding analysis confirmed the modifiedTiO2 coated P-HSM, which can effectively reduce the band gap and control the agglomeration of titanium dioxide, i.e., suitable to degrade RhB. Under UV irradiation, PDA/PEI @TiO2@P-HSM can remove RhB up to 90 % in 100 min. The photocatalytic degradation process conforms to the Langmuir-Hinshelwood quasi-primary equation. The composite exhibited excellent stability and recycling i.e., a high removal effect, with a removal rate of up to 60 % after seven cycles of reaction.

Identification and Validation of the Diagnostic Markers for Inflammatory Bowel Disease by Bioinformatics Analysis and Machine Learning.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract which is mediated by the inappropriate immune responses. This study was aimed to identify novel diagnostic biomarkers for diagnosis of IBD and explore the relationship between the diagnostic biomarkers and infiltrated immune cells. GSE38713, GSE53306, and GSE75214 downloaded from the Gene Expression Omnibus (GEO) database were split into training and testing sets. Differentially expressed genes (DEGs) were screened using the "limma" package. Gene Ontology (GO) and KEGG pathway enrichment analysis of DEGs were performed by clusterProfiler package. The LASSO regression and support vector machine recursive feature elimination (SVM-RFE) algorithms were conducted to identify novel diagnostic biomarkers. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic value of the candidate biomarkers. The relationship of the candidate biomarkers and infiltrating immune cells in IBD were evaluated by CIBERSOTR. Quantitative Real-Time PCR (qRT-PCR) was applied to measure the expression level of the biomarkers in IBD. A total of 289 dysregulated genes were identified as DEGs in IBD. These DEGs were significantly enriched in chemokine signaling pathway and cytokine-cytokine receptor interaction. RHOU was identified as a critical diagnostic gene in IBD, which was confirmed using ROC curve and qRT-PCR assays. Immune cell infiltration analysis showed that RHOU was correlated with macrophages M2, dendritic cells resting, mast cells resting, T cells CD4 memory resting, macrophages M0, and mast cells activated. Our results imply that RHOU may be a potential diagnostic biomarker for IBD.

Circulating cytokines and alcoholic liver disease: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Increased inflammation in the liver during ethanol exposure is a major feature of alcoholic liver disease (ALD). An important contributing component to the development of ALD is the inflammatory response brought on by immunological response, however the connection between individual circulating cytokines and ALD is still unclear. To ascertain the causation, we conducted a two-sample bidirectional Mendelian randomization research. METHODS: We extracted 41 cytokines and growth factors of 8293 Europeans and ALD cases of the same ethnicity (1416 cases and 217,376 controls) from the Genome-Wide Association Studies (GWAS) database for two-sample bidirectional MR analysis. RESULTS: Our analyses suggest that higher interleukin-7 (IL-7) levels are associated with an increased risk of ALD (p = 0.028, OR = 1.191,95% CI = 1.019-1.392), while tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a protective factor for ALD (p = 0.032, OR = 0.863, 95% CI = 0.754-0.988) which can reduce the risk of disease occurrence. In addition, genetically predicted ALD does not affect the expression of circulating cytokines regulators. CONCLUSIONS: Our study supports that cytokines play a pivotal role in the pathogenesis of ALD. To determine the mechanisms and pathways of action of these biomarkers, further basic research is required to ensure their clinical suitability for preventing and treating ALD.

Construction and validation of a mitochondria-associated genes prognostic signature and immune microenvironment characteristic of sepsis.

BACKGROUND: Sepsis is a common critical condition seen in clinical settings, with mitochondrial dysfunction playing an important role in the progression of sepsis. However, a mitochondrial prognosis model related to sepsis has not been established yet, and the relationship between the sepsis immune microenvironment and mitochondria remains unclear. METHODS: Sepsis prognostic mitochondria-associated genes (MiAGs) were screened by univariate Cox, multivariate Cox, and LASSO analysis from the GEO dataset. Consensus Cluster was used to analyze MiAGs-based molecular subtypes for sepsis. The ESTIMATE and ssGSEA algorithms were used to analyze the situation of sepsis immune cell infiltration and its relation to MiAGs. Further, MiAGs score was calculated to construct a sepsis prognosis risk model to predict the prognosis of sepsis patients. Clinical blood samples were used to investigate the expression level of selected MiAGs in sepsis. Single-cell sequencing analysis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and ATP detection were used to verify the influence of MiAGs on mitochondrial dysfunction in sepsis. RESULTS: A total of 5 MiAGs of sepsis were screened. Based on MiAGs, sepsis MiAGs subtypes were analyzed, where Cluster A had a better prognosis than Cluster B, and there were significant differences in immune infiltration between the two clusters. The sepsis mitochondrial prognosis model suggested that the high MiAG score group had a shorter survival time compared to the low MiAG score group. Significant differences were also observed in the immune microenvironment between the high and low MiAG score groups. Prognostic analysis and the Nomogram indicated that the MiAG score is an independent prognostic factor in sepsis. Single-cell sequencing analysis exhibited the possible influence of MiAGs on the mitochondrial function of monocytes. Finally, the downregulation of the COX7B could effectively improve mitochondrial function in the LPS-stimulated sepsis model. CONCLUSION: Our findings suggest that MiAGs can be used to predict the prognosis of sepsis and that regulating the mitochondrial prognostic gene COX7B can effectively improve the mitochondrial function of immune cells in sepsis.

Combination treatment with telitacicept, cyclophosphamide and glucocorticoids for severe Granulomatous polyangiitis: a case report and literature review.

Granulomatous polyangiitis (GPA) is a rare autoimmune disease that can involve multiple systems throughout the body, including the ear, nose, upper and lower respiratory tracts. It is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Telitacicept is a novel recombinant fusion protein targeting B-lymphocyte stimulator (BLyS). Telitacicept can inhibit the development and maturation of abnormal B cells by blocking BLyS, and inhibit the production of antibodies by abnormal plasma cells by blocking APRIL (A proliferation-inducing ligand), which is expected to become a new drug for the treatment of GPA. We report a 64-year-old man diagnosed at our hospital with GPA involving multiple systems including kidneys, lungs, nose and ears. Renal involvement was severe, with a clinical characteristic of rapidly progressive glomerulonephritis and a pathologic manifestation of crescentic nephritis with plasma cell infiltration. The patient was treated with hormones, immunoglobulins and cyclophosphamide (CYC) with the addition of telitacicept and a rapid reduction in hormone dosage. The patient's renal function improved significantly within a short period of time, and his hearing and lung lesions improved significantly. At the same time, he did not develop serious infections and other related complications. Our report suggests that short-term control of the patient's conditions is necessary in GPA patients with organ-threatening disease. Telitacicept combined with CYC and glucocorticoids may be an induction therapy with safety and feasibility. However, more clinical trials are needed to validate the efficacy and safety of the therapeutic regimen.

Research progress of traditional Chinese medicine in improving hepatic fibrosis based on inhibiting pathological angiogenesis.

Hepatic fibrosis is the formation of scar tissue in the liver. This scar tissue replaces healthy liver tissue and can lead to liver dysfunction and failure if left untreated. It is usually caused by chronic liver disease, such as hepatitis B or C, alcohol abuse, or non-alcoholic fatty liver disease. Pathological angiogenesis plays a crucial role in the development of hepatic fibrosis by promoting the growth of new blood vessels in the liver. These new vessels increase blood flow to the damaged areas of the liver, which triggers the activation of hepatic stellate cells (HSCs). HSCs are responsible for producing excess collagen and other extracellular matrix proteins that contribute to the development of fibrosis. Pathological angiogenesis plays a crucial role in the development of hepatic fibrosis by promoting the growth of new blood vessels in the liver. These new vessels increase blood flow to the damaged areas of the liver, which triggers the activation of HSCs. HSCs are responsible for producing excess collagen and other extracellular matrix proteins that contribute to the development of fibrosis. Traditional Chinese medicine (TCM) has been found to target pathological angiogenesis, thereby providing a potential treatment option for hepatic fibrosis. Several studies have demonstrated that TCM exhibits anti-angiogenic effects by inhibiting the production of pro-angiogenic factors, such as vascular endothelial growth factor and angiopoietin-2, and by reducing the proliferation of endothelial cells. Reviewing and highlighting the unique TCM recognition of treating hepatic fibrosis by targeting pathological angiogenesis may shed light on future hepatic fibrosis research.

Progress on traditional Chinese medicine in improving hepatic fibrosis through inhibiting oxidative stress.

Hepatic fibrosis is a common pathological process that occurs in the development of various chronic liver diseases into cirrhosis and liver cancer, characterized by excessive deposition of the extracellular matrix. In the past, hepatic fibrosis was thought to be a static and irreversible pathological process. In recent years, with the rapid development of molecular biology and the continuous in-depth study of the liver at the microscopic level, more and more evidence has shown that hepatic fibrosis is a dynamic and reversible process. Therefore, it is particularly important to find an effective, simple, and inexpensive method for its prevention and treatment. Traditional Chinese medicine (TCM) occupies an important position in the treatment of hepatic fibrosis due to its advantages of low adverse reactions, low cost, and multi-target effectiveness. A large number of research results have shown that TCM monomers, single herbal extracts, and TCM formulas play important roles in the prevention and treatment of hepatic fibrosis. Oxidative stress (OS) is one of the key factors in the occurrence and development of hepatic fibrosis. Therefore, this article reviews the progress in the understanding of the mechanisms of TCM monomers, single herbal extracts, and TCM formulas in preventing and treating hepatic fibrosis by inhibiting OS in recent years, in order to provide a reference and basis for drug therapy of hepatic fibrosis.

4-Electron redox enabled by a perylene diimide containing side-chain amines for efficient organic cathode development.

A perylene diimide containing side-chain amines (PDIN) was studied as an organic cathode for application in lithium batteries, showing a high capacity of 174 mA h g-1. The chemical structures, experimental results, and calculation analyses verify that PDIN performed a 4-electron redox reaction jointly involving its CO and side-chain amine groups. This study promotes the development of organic cathodes with multi-electron redox reactions.

Dose-sparing effect of lapatinib co-administered with a high-fat enteral nutrition emulsion: preclinical pharmacokinetic study.

Background: Lapatinib is an oral small-molecule tyrosine kinase inhibitor indicated for advanced or metastatic HER2-positive breast cancer. In order to reduce the treatment cost, a high-fat enteral nutrition emulsion TPF-T was selected as a dose-sparing agent for lapatinib-based therapies. This study aimed to investigate the effect of TPF-T on lapatinib pharmacokinetics. Methods: First, a simple and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to quantitatively evaluate lapatinib in rabbit plasma. The method was fully validated according to the China Pharmacopoeia 2020 guidance. Rabbits and rats were chosen as the animal models due to their low and high bile flows, respectively. The proposed LC-MS/MS method was applied to pharmacokinetic studies of lapatinib, with or without TPF-T, in rabbit and rat plasma. Results: The LC-MS/MS method revealed high sensitivity and excellent efficiency. In the rabbit model, co-administration with TPF-T resulted in a 32.2% increase in lapatinib exposure. In the rat model, TPF-T had minimal influence on the lapatinib exposure. In both models, TPF-T was observed to significantly elevate lapatinib concentration in the absorption phase. Conclusion: Co-administration with TPF-T had a moderate effect on increasing exposure to lapatinib. Dose sparing using a high-fat liquid diet is potentially feasible for lapatinib-based therapies.

Development of anoikis-related long non-coding RNA signature associated with prognosis and immune landscape in cutaneous melanoma patients.

BACKGROUND: Anoikis is involved in many critical biological processes in tumors; however, function in CM is still unknown. In this study, the relevance between Anoikis-related lncRNAs (ARLs) and the clinicopathological characteristics of patients with CM was comprehensively assessed. METHODS: Through analysis of TCGA dataset, ARLs were identified by using TCGA dataset. Based on the ARLs, a risk model was established to anticipate the prognosis of patients with CM, besides, the prediction accuracy of the model was evaluated. The immune infiltration landscape of patients with CM was assessed comprehensively, and the correlation between ARLs and immunity was elucidated. Immunotherapy and drug sensitivity analyses were applied to analyze the treatment response in patients with CM with diverse risk scores. Different subgroups were distinguished among the patients using consensus cluster analysis. RESULTS: A risk model based on six ARLs was set up to obtain an accurate prediction of the prognosis of patients with CM. There were distinctions in the immune landscape among CM patients with diverse risk scores and subgroups. Six prognosis-related ARLs were highly correlated with the number of immune cells. Patients with CM with different risk scores have various sensitivities to immunotherapy and antitumor drug treatments. CONCLUSION: Our newly risk model associated with ARLs has considerable prognostic value for patients with CM. Not only has the risk model high prediction accuracy but it also indicates the immune status of CM patients, which will provide a new direction for the individualized therapy of patients with CM.