Deletion of Tgm2 suppresses BMP-mediated hepatocyte-to-cholangiocyte metaplasia in ductular reaction.

Transglutaminase 2 (Tgm2) plays an essential role in hepatic repair following prolonged toxic injury. During cholestatic liver injury, the intrahepatic cholangiocytes undergo dynamic tissue expansion and remodelling, referred to as ductular reaction (DR), which is crucial for liver regeneration. However, the molecular mechanisms governing the dynamics of active cells in DR are still largely unclear. Here, we generated Tgm2-knockout mice (Tgm2-/-) and Tgm2-CreERT2-Rosa26-mTmG flox/flox (Tgm2CreERT2-R26T/Gf/f) mice and performed a three-dimensional (3D) collagen gel culture of mouse hepatocytes to demonstrate how Tgm2 signalling is involved in DR to remodel intrahepatic cholangiocytes. Our results showed that the deletion of Tgm2 adversely affected the functionality and maturity of the proliferative cholangiocytes in DR, thus leading to more severe cholestasis during DDC-induced liver injury. Additionally, Tgm2 hepatocytes played a crucial role in the regulation of DR through metaplasia. We unveiled that Tgm2 regulated H3K4me3Q5ser via serotonin to promote BMP signalling activation to participate in DR. Besides, we revealed that the activation or inhibition of BMP signalling could promote or suppress the development and maturation of cholangiocytes in DDC-induced DR. Furthermore, our 3D collagen gel culture assay indicated that Tgm2 was vital for the development of cholangiocytes in vitro. Our results uncovered a considerable role of BMP signalling in controlling metaplasia of Tgm2 hepatocytes in DR and revealed the phenotypic plasticity of mature hepatocytes.

g-C3N4 as ballistic electron transport "Tunnel" in CsPbBr3-based ternary photocatalyst for gas phase CO2 reduction.

Perovskite CsPbBr3 quantum dot shows great potential in artificial photosynthesis, attributed to its outstanding optoelectronic properties. Nevertheless, its photocatalytic activity is hindered by insufficient catalytic active sites and severe charge recombination. In this work, a CsPbBr3@Ag-C3N4 ternary heterojunction photocatalyst is designed and synthesized for high-efficiency CO2 reduction. The CsPbBr3 quantum dots and Ag nanoparticles are chemically anchored on the surface of g-C3N4 sheets, forming an electron transfer tunnel from CsPbBr3 quantum dots to Ag nanoparticles via g-C3N4 sheets. The resulting CsPbBr3@Ag-C3N4 ternary photocatalyst, with spatial separation of photogenerated carriers, achieves a remarkable conversion rate of 19.49 µmol·g-1·h-1 with almost 100 % CO selectivity, a 3.13-fold enhancement in photocatalytic activity as compared to CsPbBr3 quantum dots. Density functional theory calculations reveal the rapid CO2 adsorption/activation and the decreased free energy (0.66 eV) of *COOH formation at the interface of Ag nanoparticles and g-C3N4 in contrast to the g-C3N4, leading to the excellent photocatalytic activity, while the thermodynamically favored CO desorption contributes to the high CO selectivity. This work presents an innovative strategy of constructing perovskite-based photocatalyst by modulating catalyst structure and offers profound insights for efficient CO2 conversion.

Establishment and analysis of artificial neural network diagnosis model for coagulation-related molecular subgroups in coronary artery disease.

Background: Coronary artery disease (CAD) is the most common type of cardiovascular disease and cause significant morbidity and mortality. Abnormal coagulation cascade is one of the high-risk factors in CAD patients, but the molecular mechanism of coagulation in CAD is still limited. Methods: We clustered and categorized 352 CAD paitents based on the expression patterns of coagulation-related genes (CRGs), and then we explored the molecular and immunological variations across the subgroups to reveal the underlying biological characteristics of CAD patients. The feature genes between CRG-subgroups were further identified using a random forest model (RF) and least absolute shrinkage and selection operator (LASSO) regression, and an artificial neural network prediction model was constructed. Results: CAD patients could be divided into the C1 and C2 CRG-subgroups, with the C1 subgroup highly enriched in immune-related signaling pathways. The differential expressed genes between the two CRG-subgroups (DE-CRGs) were primarily enriched in signaling pathways connected to signal transduction and energy metabolism. Subsequently, 10 feature DE-CRGs were identified by RF and LASSO. We constructed a novel artificial neural network model using these 10 genes and evaluated and validated its diagnostic performance on a public dataset. Conclusion: Diverse molecular subgroups of CAD patients may each have a unique gene expression pattern. We may identify subgroups using a few feature genes, providing a theoretical basis for the precise treatment of CAD patients with different molecular subgroups.

Role of differentiated embryo-chondrocyte expressed gene 2 in immunity.

Differentiated embryo-chondrocyte expressed gene 2 (DEC2) is a member of the basic helix-loop-helix (bHLH) subfamily of transcription factors. DEC2 is implicated in tumor immunotherapy, immune system function regulation, and autoimmune diseases. DEC2 enhances Th2 cell differentiation by regulating the IL-2 and IL-4 signaling pathways and mediates the growth of B-1a cells, thereby promoting the occurrence and development of inflammatory responses. In this study, we review the reported roles of DEC2, including the regulation of immune cell differentiation and cytokine production in various cells in humans, and discuss its potential in treating autoimmune diseases and tumors.

A novel approach to evaluation of tumor response for advanced pulmonary adenocarcinoma using the intertumoral heterogeneity response score.

Treatment response and prognosis estimation in advanced pulmonary adenocarcinoma are challenged by the significant heterogeneity of the disease. The current Response Evaluation Criteria in Solid Tumors (RECIST) criteria, despite providing a basis for solid tumor response evaluation, do not fully encompass this heterogeneity. To better represent these nuances, we introduce the intertumoral heterogeneity response score (THRscore), a measure built upon and expanding the RECIST criteria. This retrospective study included patients with 3-10 measurable advanced lung adenocarcinoma lesions who underwent first-line chemotherapy or targeted therapy. The THRscore, derived from the coefficient of variation in size for each measurable tumor before and 4-6 weeks posttreatment, unveiled a correlation with patient outcomes. Specifically, a high THRscore was associated with shorter progression-free survival, lower tumor response rate, and a higher tumor mutation burden. These associations were further validated in an external cohort, confirming THRscore's effectiveness in stratifying patients based on progression risk and treatment response, and enhancing the utility of RECIST in capturing complex tumor behaviors in lung adenocarcinoma. These findings affirm the promise of THRscore as an enhanced tool for tumor response assessment in advanced lung adenocarcinoma, extending the RECIST criteria's utility.

Development of Injectable Thermosensitive Nanocomposite Hydrogel for Ratiometric Drug Delivery to Treat Drug Resistant Chondrosarcoma In Vivo.

Chondrosarcoma(CS), a prevalent primary malignant bone tumor, frequently exhibits chemotherapy resistance attributed to upregulated anti-apoptosis pathways such as the Bcl-2 family. In this manuscript, a new strategy is presented to augment chemosensitivity and mitigate systemic toxicity by harnessing a nano-enabled drug delivery hydrogel platform. The platform utilizes "PLGA-PEG-PLGA", an amphiphilic triblock copolymer combining hydrophilic polyethylene glycol (PEG) and hydrophobic polylactide glycolide (PLGA) blocks, renowned for its properties conducive to crafting a biodegradable, temperature-sensitive hydrogel. This platform is tailored to encapsulate a ratiometrically designed dual-loaded liposomes containing a first-line chemo option for CS, Doxorubicin (Dox), plus a calculated amount of small molecule inhibitor for anti-apoptotic Bcl-2 pathway, ABT-737. In vitro and in vivo evaluations demonstrate successful Bcl-2 suppression, resulting in the restoration of Dox sensitivity, evident through impeded tumor growth and amplified necrosis rates at the tumor site. This delivery system showcases remarkable thermal responsiveness, injectability, and biodegradability, all finely aligned with the clinical demands of CS treatment. Collectively, this study introduces a transformative avenue for tackling drug resistance in CS chemotherapy, offering significant clinical potential.

Tomato SlMAPK3 Modulates Cold Resistance by Regulating the Synthesis of Raffinose and the Expression of SlWRKY46.

Mitogen-activated protein kinase (MAPK) cascades and raffinose have been observed to increase in plants exposed to cold. However, it remains elusive whether and how MAPK regulates raffinose synthesis under cold stress. Here, overexpression of SlMAPK3 promoted the accumulation of galactinol and raffinose under cold stress, while CRISPR/Cas9-mediated mutants showed the opposite results. Moreover, SlMAPK3 promoted the expression of SlWRKY46 at low temperatures and interacted with SlWRKY46 protein. Overexpression of SlWRKY46 enhanced cold resistance. Furthermore, SlWRKY46 directly bound to the promoter of SlGols1 to enhance its expression and promoted the accumulation of raffinose. Virus-induced gene-silencing (VIGS)-mediated knockdown of SlGols1 remarkably elevated cold sensitivity and reduced raffinose content. Meanwhile, exogenous supplementation of raffinose could improve the cold tolerance of tomato plants. Thus, our data indicates that SlMAPK3 modulates cold resistance by regulating raffinose content and SlWRKY46 expression. SlWRKY46 also promotes the accumulation of raffinose by inducing the expression of SlGols1.

The early development of offspring born to women with polycystic ovary syndrome: Insights from a prospective birth cohort study in Southwestern China.

PURPOSE: This prospective cohort study aimed to investigate the effect of maternal polycystic ovary syndrome (PCOS) on the offspring early development. METHODS: A total of 91 mother-child pairs, consisting of 33 PCOS and 58 non-PCOS, were recruited. Peripheral blood tests were performed during 12-16, 24-28, and 32-36 weeks of gestation. Ages & Stages Questionnaires (ASQ) were utilized to assess the motor development of offspring at 27 months of age. Logistic regression models were employed to compare groups and control confounding variables. RESULTS: Women with PCOS had a higher level of testosterone and free androgen index than the non-PCOS group in all three detection windows. There were no intergroup differences in any of the five domains of specific ASQ domain scores or the body measurements of the offspring at 27 months old. Stratification by sex of offspring suggested that no significant differences were detected in the male offspring. However, in the female offspring, the PCOS group exhibited lower gross motor scores in female offspring than the non-PCOS group (48.1 ± 11.8 vs. 55.2 ± 8.1, P = 0.027), as well as lower fine motor scores (48.5 ± 8.5 vs. 53.6 ± 11.0, P = 0.028). The gross motor score of female offspring in the PCOS group remained lower even after adjustments. Each 1 ng/mL increase in testosterone at 12-16 weeks of gestation was associated with a decrease in gross motor score of female offspring by 12.2 (95% CI = -23.3 to -1.0, P = 0.038). The highest tertile of testosterone at 12-16 weeks of gestation was associated with a 7.75-point decrease in gross motor score of female offspring compared to the lowest tertile of testosterone (95% CI = -14.9 to -0.6, P = 0.040), with a significant linear trend observed (P for trend = 0.031). CONCLUSIONS: The findings of this study suggest that maternal PCOS could exert a negative influence on the gross motor development of female offspring, potentially associated with intrauterine androgen exposure during the early stages of pregnancy.

Recent Advances in Dissecting the Function of Ethylene in Interaction between Host and Pathogen.

Pathogens influence the growth and development of plants, resulting in detrimental damage to their yields and quality. Ethylene, a gaseous phytohormone, serves a pivotal function in modulating diverse physiological processes in plants, including defense mechanisms against pathogen invasion. Ethylene biosynthesis is involved in both plants and pathogens. Recent empirical research elucidates the intricate interactions and regulatory mechanisms between ethylene and pathogens across various plant species. In this review, we provide a comprehensive overview of the latest findings concerning ethylene's role and its regulatory networks in host-pathogen interactions. Additionally, we explore the crosstalk between ethylene and other phytohormones. Points regarding ethylene emission and its modulation by pathogens are also emphasized. Moreover, we also discuss potential unresolved issues in the field that warrant further investigation.

Comprehensive transcriptional analysis of early dorsal skin development in pigs.

Porcine skin is similar to human skin in physiology, anatomy and histology and is often used as a model animal for human skin research. There are few studies on the transcriptome aspects of pig skin during the embryonic period. In this study, RNA sequencing was performed on the dorsal skin of Chenghua sows at embryonic day 56 (E56), embryonic day 76 (E76), embryonic day 105 (E105), and 3 days after birth (D3) to explore RNA changes in pig dorsal skin at four ages. A number of skin-related differential genes were identified by intercomparison between RNAs at four time points, and KEGG functional analysis showed that these differential genes were mainly enriched in metabolic and developmental, immune, and disease pathways, and the pathways enriched in GO analysis were highly overlapping. Collagen is an important part of the skin, with type I collagen making up the largest portion. In this study, collagen type I alpha 1 (COL1A1) and collagen type I alpha 2 (COL1A2) were significantly upregulated at four time points. In addition, lncRNA-miRNA-mRNA and miRNA-circRNA coexpression networks were constructed. The data obtained may help to explain age-related changes in transcriptional patterns during skin development and provide further references for understanding human skin development at the molecular level.

Synergistic Chemoimmunotherapy Augmentation via Sequential Nanocomposite Hydrogel-Mediated Reprogramming of Cancer-Associated Fibroblasts in Osteosarcoma.

In osteosarcoma, immunotherapy often faces hurdles posed by cancer-associated fibroblasts (CAFs) that secrete dense extracellular matrix components and cytokines. Directly removing CAFs may prove ineffective and even promote tumor metastasis. To address this challenge, a sequential nanocomposite hydrogel that reshapes CAF behavior is developed, enhancing tumor-infiltrating T-cells in osteosarcoma. The approach utilizes an injectable blend of carboxymethyl chitosan and tetrabasic polyethylene glycol, forming a hydrogel for controlled release of a potent CAF suppressor (Nox4 inhibitor, Nox4i) and liposomal Doxorubicin (L-Dox) to induce immunogenic cell death (ICD) upon in situ administration. Nox4i effectively counters CAF activation, overcoming T-cell exclusion mechanisms, followed by programmed L-Dox release for ICD induction in stroma-rich osteosarcoma models. Combining the co-delivery gel with αPD-1 checkpoint inhibitor further enhances its effectiveness in an orthotopic osteosarcoma model. Immunophenotyping data underscore a significant boost in tumor T-cell infiltration and favorable anti-tumor immunity at the whole-animal level.

Deep Learning Radiomics Model of Dynamic Contrast-Enhanced MRI for Evaluating Vessels Encapsulating Tumor Clusters and Prognosis in Hepatocellular Carcinoma.

BACKGROUND: Vessels encapsulating tumor cluster (VETC) is a critical prognostic factor and therapeutic predictor of hepatocellular carcinoma (HCC). However, noninvasive evaluation of VETC remains challenging. PURPOSE: To develop and validate a deep learning radiomic (DLR) model of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative discrimination of VETC and prognosis of HCC. STUDY TYPE: Retrospective. POPULATION: A total of 221 patients with histologically confirmed HCC and stratified this cohort into training set (n = 154) and time-independent validation set (n = 67). FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T; DCE imaging with T1-weighted three-dimensional fast spoiled gradient echo. ASSESSMENT: Histological specimens were used to evaluate VETC status. VETC+ cases had a visible pattern (≥5% tumor area), while cases without any pattern were VETC-. The regions of intratumor and peritumor were segmented manually in the arterial, portal-venous and delayed phase (AP, PP, and DP, respectively) of DCE-MRI and reproducibility of segmentation was evaluated. Deep neural network and machine learning (ML) classifiers (logistic regression, decision tree, random forest, SVM, KNN, and Bayes) were used to develop nine DLR, 54 ML and clinical-radiological (CR) models based on AP, PP, and DP of DCE-MRI for evaluating VETC status and association with recurrence. STATISTICAL TESTS: The Fleiss kappa, intraclass correlation coefficient, receiver operating characteristic curve, area under the curve (AUC), Delong test and Kaplan-Meier survival analysis. P value <0.05 was considered as statistical significance. RESULTS: Pathological VETC+ were confirmed in 68 patients (training set: 46, validation set: 22). In the validation set, DLR model based on peritumor PP (peri-PP) phase had the best performance (AUC: 0.844) in comparison to CR (AUC: 0.591) and ML (AUC: 0.672) models. Significant differences in recurrence rates between peri-PP DLR model-predicted VETC+ and VETC- status were found. DATA CONCLUSIONS: The DLR model provides a noninvasive method to discriminate VETC status and prognosis of HCC patients preoperatively. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Transition of allele-specific DNA hydroxymethylation at regulatory loci is associated with phenotypic variation in monozygotic twins discordant for psychiatric disorders.

BACKGROUND: Major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD) are complex genetic mental illnesses. Their non-Mendelian features, such as those observed in monozygotic twins discordant for SCZ or BPD, are likely complicated by environmental modifiers of genetic effects. 5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark in gene regulation, and whether it is linked to genetic variants that contribute to non-Mendelian features remains largely unexplored. METHODS: We combined the 5hmC-selective chemical labeling method (5hmC-seq) and whole-genome sequencing (WGS) analysis of peripheral blood DNA obtained from monozygotic (MZ) twins discordant for SCZ or BPD to identify allelic imbalances in hydroxymethylome maps, and examined association of allele-specific hydroxymethylation (AShM) transition with disease susceptibility based on Bayes factors (BF) derived from the Bayesian generalized additive linear mixed model. We then performed multi-omics integrative analysis to determine the molecular pathogenic basis of those AShM sites. We finally employed luciferase reporter, CRISPR/Cas9 technology, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), PCR, FM4-64 imaging analysis, and RNA sequencing to validate the function of interested AShM sites in the human neuroblastoma SK-N-SH cells and human embryonic kidney 293T (HEK293T) cells. RESULTS: We identified thousands of genetic variants associated with AShM imbalances that exhibited phenotypic variation-associated AShM changes at regulatory loci. These AShM marks showed plausible associations with SCZ or BPD based on their effects on interactions among transcription factors (TFs), DNA methylation levels, or other epigenomic marks and thus contributed to dysregulated gene expression, which ultimately increased disease susceptibility. We then validated that competitive binding of POU3F2 on the alternative allele at the AShM site rs4558409 (G/T) in PLLP-enhanced PLLP expression, while the hydroxymethylated alternative allele, which alleviated the POU3F2 binding activity at the rs4558409 site, might be associated with the downregulated PLLP expression observed in BPD or SCZ. Moreover, disruption of rs4558409 promoted neural development and vesicle trafficking. CONCLUSION: Our study provides a powerful strategy for prioritizing regulatory risk variants and contributes to our understanding of the interplay between genetic and epigenetic factors in mediating SCZ or BPD susceptibility.

Cerebrospinal fluid circulating tumor DNA contributes to the detection and characterization of leptomeningeal metastasis in non-small cell lung cancer.

PURPOSE: Cerebrospinal fluid (CSF) has revealed the unique genetic characteristics of leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC). However, the research in this area is still very limited. METHODS: Patients with LM from NSCLC (n = 80) were retrospectively analyzed. Circulating tumor DNA (ctDNA) in CSF was tested by next-generation sequencing (NGS), with paired extracranial tissue or plasma samples included for comparison. An independent non-LM cohort (n = 100) was also analyzed for comparative purposes. Clinical outcomes were compared with Kaplan-Meier log-rank test and Cox proportional hazards methodologies. RESULTS: An overwhelming 93.8% of patients carried druggable mutations in NSCLC LM, with EGFR (78.8%) being the most prevalent. Notably, 4 patients who tested negative for driver genes in extracranial samples surprisingly showed EGFR mutations in their CSF and subsequently benefited from targeted therapy. There was a clear difference in genetic profiles between CSF and extracranial samples, with CSF showing more driver gene detections, increased Copy Number Variations (CNVs), and varied resistance mechanisms among individuals. Abnormalities in cell-cycle regulatory molecules were highly enriched in LM (50.9% vs 31.0%, p = 0.017), and CDKN2A/2B deletions were identified as an independent poor prognostic factor for LM patients, with a significant reduction in median OS (p = 0.013), supported by multivariate analysis (HR 2.63, 95% CI 1.32-5.26, p = 0.006). CONCLUSIONS: CSF-based ctDNA analysis is crucial for detecting and characterizing genetic alterations in NSCLC LM. The distinct genetic profiles in CSF and extracranial tissues emphasize the need for personalized treatment approaches.

Baseline C-reactive protein predicts efficacy of the first-line immune checkpoint inhibitors plus chemotherapy in advanced lung squamous cell carcinoma: a retrospective, multicenter study.

AIMS: To investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC). MATERIALS AND METHODS: In this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups. RESULTS: Of the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12-2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13-4.44; p = 0.033). CONCLUSION: In patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.

Lowering Hippocampal miR-29a Expression Slows Cognitive Decline and Reduces Beta-Amyloid Deposition in 5×FAD Mice.

microRNA-29a (miR-29a) increases with age in humans and mice, and, in the brain, it has a role in neuronal maturation and response to inflammation. We previously found higher miR-29a levels in the human brain to be associated with faster antemortem cognitive decline, suggesting that lowering miR-29a levels could ameliorate memory impairment in the 5×FAD AD mouse model. To test this, we generated an adeno-associated virus (AAV) expressing GFP and a miR-29a "sponge" or empty vector. We found that the AAV expressing miR-29a sponge functionally reduced miR-29a levels and improved measures of memory in the Morris water maze and fear condition paradigms when delivered to the hippocampi of 5×FAD and WT mice. miR-29a sponge significantly reduced hippocampal beta-amyloid deposition in 5×FAD mice and lowered astrocyte and microglia activation in both 5×FAD and WT mice. Using transcriptomic and proteomic sequencing, we identified Plxna1 and Wdfy1 as putative effectors at the transcript and protein level in WT and 5×FAD mice, respectively. These data indicate that lower miR-29a levels mitigate cognitive decline, making miR-29a and its target genes worth further evaluation as targets to mitigate Alzheimer's disease (AD).

Effects of intrathecal pemetrexed on the survival of patients with leptomeningeal metastasis from lung adenocarcinoma: a propensity score matching analysis.

PURPOSE: To explore the impact of intrathecal pemetrexed (IP) on the survival of lung adenocarcinoma (LUAC) patients with leptomeningeal metastasis (LM). METHODS: We analyzed patients with LUAC and LM who received systemic therapy after LM diagnosis at the Fujian Cancer Hospital between July 2018 and March 2022. Patients who underwent IP were assigned to the IP group; those without IP treatment were designated as the non-IP group. Propensity score matching (PSM) was performed between the two groups. RESULTS: 165 patients were enrolled: 83 and 82 in the IP and non-IP groups, respectively. After 1:1 PSM, we included 114 patients in the matched cohort. Median overall survival (OS) was 13.2 months (95% CI 10.8-15.6 months) in the IP group versus 10.1 months (95% CI 5.3-14.9 months) in the non-IP group (P = 0.488). Only Eastern Cooperative Oncology Group Performance Status (ECOG PS) was confirmed as an independent predictor for OS in the matched cohort (hazard ratio (HR) 2.03; P = 0.023). Multivariate competing-risks analysis showed that IP significantly correlated with central nervous system-related death (HR 0.31; P = 0.046). When stratified by ECOG PS, IP improved survival in patients with poor ECOG PS (PS = 2) (14.3 months vs. 1.6 months; P = 0.003). CONCLUSIONS: Intrathecal pemetrexed did not enhance OS for the entire LUAC patient with LM compared to non-intrathecal chemotherapy. However, it exhibited the potential to reduce the risk of central nervous system-related mortality and improve survival in patients with poor ECOG PS.

Efficacy and safety of telitacicept in patients with systemic lupus erythematosus: a multicentre, retrospective, real-world study.

OBJECTIVE: To examine the efficacy and safety of telitacicept in the treatment of patients with SLE in everyday clinical practice. METHODS: Seventy-two patients with active SLE who received telitacicept for more than 24 weeks at multiple centres in China between 2019 and 2022 were retrospectively identified. Twenty-one of these patients received 52 continuous weeks of treatment with telitacicept. Treatment outcomes were analysed separately according to whether patients had renal or haematological abnormalities. Trajectory analysis was performed to identify patients with a limited response. Factors contributing to a limited response were explored by multivariable logistic regression analysis. RESULTS: After treatment with telitacicept for 4, 12, 24 and 52 weeks, 22.22%, 54.17%, 72.22% and 80.95% of patients, respectively, achieved an SLE Responder Index 4; 8.33%, 26.39%, 34.72% and 47.62% achieved a Lupus Low Disease Activity State; and 0%, 4.17%, 8.33% and 23.81% achieved remission. Significant decreases in serum IgA, IgG and IgM levels were observed at 4 weeks and showed a downward trend at 12, 24 and 52 weeks. The median 24-hour urinary protein declined from 1323.5 mg to 224.0 mg in patients with lupus nephritis after treatment with telitacicept for 52 weeks. Furthermore, a large proportion of patients (10 of 13) with haematological abnormalities recovered after 52 weeks of treatment with telitacicept. No severe adverse events were reported during the observation period. Age appeared to have a negative impact on treatment efficacy. CONCLUSIONS: Telitacicept demonstrated favourable efficacy and safety in patients with active SLE and improved the renal and haematological manifestations of the disease.