High-dose Furmonertinib in patients with EGFR-mutated non-small cell lung cancer and leptomeningeal metastases: A prospective real-world study.

INTRODUCTION: Leptomeningeal metastasis (LM) is one of the most severe complications of non-small cell lung cancer (NSCLC). Furmonertinib is a pan-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with a high rate of brain penetration and a wide therapeutic window. Here, we evaluated the efficacy and safety of high-dose furmonertinib in patients with EGFR-mutated NSCLC and LM. METHODS: This prospective real-world study included patients with EGFR-mutated NSCLC and LM treated with a high-dose furmonertinib (240 mg once daily) as a monotherapy or in combination with other treatments. The primary endpoint was overall survival (OS), and the secondary endpoints included time to treatment discontinuation (TTD) and clinical response rate. Additional efficacy evaluations included changes in brain magnetic resonance imaging (MRI) by the RANO-LM radiologic criteria. We also introduced next generation sequencing (NGS)-based assays to evaluate genomic and epigenomic features of cell-free DNA (cfDNA) in patients' cerebrospinal fluid (CSF) samples and to analyze their associations with patient outcomes. RESULTS: We enrolled 48 patients, of whom 35 (72.9%) had received third-generation EGFR-TKIs. The median OS was 8.43 months (95%CI, 5.48 to 11.39 months), while the median TTD was 8.27 months (95%CI, 5.40 to 11.14 months), and the clinical response rate was 75%. The LM objective response rate (ORR) and disease control rate (DCR) assessed with RANO-LM radiologic criteria were 50.0% and 92.1%, respectively. The adverse event profiles were consistent with previous reports of furmonertinib. Briefly, 22 (45.8%) had adverse events (AEs) possibly related to furmonertinib and three (6.3%) had a grade 3-elevated aminotransaminase or nausea or leucopenia, leading to dose reduction to 160 mg daily. Furthermore, methylation analysis of cfDNA in CSF showed that there was a significant correlation between the changes of aberrant methylated fragments (AMFs) from lung cancer cells and the response of the patients. Meanwhile, the copy number burden (CNB) scores derived from the low-pass whole genome sequencing (LP-WGS) assay may offer another objective and effective method for the diagnosis and evaluation of treatment efficacy in LM. CONCLUSION: In the real world, the high-dose furmonertinib-based treatment may potentially have clinical efficacy and tolerable safety in patients of EGFR-mutated NSCLC with LM, even in patients previously treated with other third-generation EGFR-TKIs. Methylation and CNB analysis of cfDNA in CSF may be considered objective indicators for the diagnosis of LM and evaluation of treatment response.

Posttreatment experiences of reproductive concerns among young breast cancer survivors: A descriptive phenomenological study.

PURPOSE: The long-term fertility impact of cancer treatments is a significant concern for young breast cancer survivors. These reproductive concerns often become a persistent source of stress, negatively affecting their quality of life. This study aims to explore the reproductive concerns experienced by young breast cancer survivors post-treatment and the factors influencing their perceptions. METHODS: This phenomenological study utilized semi-structured interviews to collect data. Eighteen participants were recruited from a tertiary hospital in Mainland China. The interviews were transcribed verbatim and analysed using Colaizzi's method. RESULTS: Data analysis revealed five themes and fourteen subthemes: (1) multiple emotional burdens interwoven with concerns about fertility; (2) concerns about risks associated with reproduction; (3) dilemma of childrearing; (4) the significance of reproduction; (5) support needs from family, peers, and professionals. CONCLUSIONS: Young breast cancer survivors in China face significant challenges related to reproductive issues. Reproductive health is a crucial aspect of breast cancer survivorship care. Healthcare providers must be attentive to the reproductive concerns of survivors, recognize the importance of multidimensional support for positive adaptation, and offer tailored and ongoing interventions to manage reproductive health in young breast cancer survivors.

MiR-629-5p May serve as a biomarker for pediatric acute respiratory distress syndrome and can regulate the inflammatory response.

OBJECTIVE: Circulating microRNAs (miRNAs) are associated with pediatric acute respiratory distress syndromes (PARDS). This study analyzed the clinical significance and potential mechanism of microRNA (miR)-629-5p in PARDS. METHODS: 82 children with PARDS and 82 controls were enrolled. Serum levels of miR-629-5p were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and its diagnostic significance with respect to for PARDS in children was assessed by the receiver operating characteristic (ROC). Kaplan-Meier curve and multivariate Cox regression were utilized to examine the prognostic significance of miR-629-5p. An in vitro cell model was established using lipopolysaccharide (LPS)-induced alveolar epithelial cells A549. The cell proliferation, apoptosis, and inflammatory factors were assessed using cell counting kit-8 (CCK-8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA). miR-629-5p target genes were identified in the database and validated using the dual-luciferase report assay. RESULTS: Serum miR-629-5p levels were significantly higher in children with PARDS than in controls (P < 0.05). miR-629-5p exhibited 86.6% sensitivity and 91.5% specificity in distinguishing children with PARDS. miR-629-5p was an independent risk factor for mortality, and high levels of miR-629-5p have a poor prognosis. LPS promoted apoptosis and overproduction of inflammatory factors in A549 and upregulated miR-629-5p expression (P < 0.05); however, they were partially reversed by the weakened miR-629-5p (P < 0.05). Syndecan-4 (SDC4) is a target of miR-629-5p. The inhibition of SDC4 induced by LPS can be alleviated through the reduction of miR-629-5p. CONCLUSION: miR-629-5p serves as a diagnostic biomarker for children with PARDS and it is associated with poor prognosis. Diminished miR-629-5p may alleviate PARDS by targeting SDC4 to suppress apoptosis and inflammation of alveolar epithelial cells.

Plasma MiR-190 is a potential clinical biomarker for acute respiratory distress syndrome in children and its regulatory role in ARDS cell models by targeting KLF15.

BACKGROUND: The present research aimed to investigate the clinical value of plasma miR-190 in children with acute respiratory distress syndrome (ARDS) and the impact of miR-190 on LPS-induced ARDS cell models. METHODS: The plasma miR-190 levels were measured using real-time quantitative reverse transcription PCR (RT-qPCR). LPS-treated human pulmonary microvascular endothelial cells (HPMECs) were established and then transfected with miR-190 mimic, inhibitor, or miR-negative controls. The levels of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The effects of miR-190 on HPMEC proliferation and apoptosis were evaluated by CCK-8 assay and flow cytometry. The regulation of KLF15 by miR-190 was detected by luciferase report assay. RESULTS: The plasma miR-190 expression was increased in ARDS children and it was positively related to the severity and 28 day-survival. Plasma miR-190 could distinguish ARDS children from healthy children. Inhibition of miR-190 increased LPS-induced HPMEC cell proliferation and decreased cell apoptosis and inflammatory cytokines IL-6, IL-1ß, and TNF-α. KLF15 was a direct target of miR-190. CONCLUSION: Increased plasma miR-190 may be a clinical diagnostic and prognostic predictor for ARDS children. Inhibition of miR-190 may improve LPS-induced ARDS by increasing cell proliferation, inhibiting cell apoptosis and inflammatory response by targeting KLF15.

PD-L1 induces autophagy and primary resistance to EGFR-TKIs in EGFR-mutant lung adenocarcinoma via the MAPK signaling pathway.

Resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is a significant cause of treatment failure and cancer recurrence in non-small cell lung cancer (NSCLC). Approximately 30% of patients with EGFR-activating mutations exhibit primary resistance to EGFR-TKIs. However, the potential mechanisms of primary resistance to EGFR-TKIs remain poorly understood. Recent studies have shown that increased expression of programmed death ligand-1 (PD-L1) is associated with EGFR-TKIs resistance. Therefore, the present study aimed to investigate the mechanism of PD-L1 in primary resistance to EGFR-TKIs in EGFR-mutant lung adenocarcinoma (LUAD) cells. We found that PD-L1 was associated with poor prognosis in patients with EGFR-mutant LUAD, while the combination of EGFR-TKIs with chemotherapy could improve its therapeutic efficacy. In vitro and in vivo experiments revealed that PD-L1 promoted the proliferation and autophagy and inhibited the apoptosis of LUAD cells. Mechanistic studies demonstrated that upregulation of PD-L1 was critical in inducing autophagy through the mitogen-activated protein kinase (MAPK) signaling pathway, which was beneficial for tumor progression and the development of gefitinib resistance. Furthermore, we found that gefitinib combined with pemetrexed could synergistically enhance antitumor efficacy in PD-L1-overexpression LUAD cells. Overall, our study demonstrated that PD-L1 contributed to primary resistance to EGFR-TKIs in EGFR-mutant LUAD cells, which may be mediated by inducing autophagy via the MAPK signaling pathway. These findings not only help improve the prognosis of patients with EGFR-mutant LUAD but also provide a reference for the research of other cancer types.

Identification and Prediction of Differentially Expressed MicroRNAs Associated with Detoxification Pathways in Larvae of Spodoptera frugiperda.

Spodoptera frugiperda poses a severe threat to crops, causing substantial economic losses. The increased use of chemical pesticides has led to resistance in S. frugiperda populations. Micro ribonucleic acids (MicroRNAs or miRNAs) are pivotal in insect growth and development. This study aims to identify miRNAs across different developmental stages of S. frugiperda to explore differential expression and predict target gene functions. High-throughput sequencing of miRNAs was conducted on eggs, 3rd instar larvae, pupae, and adults. Bioinformatics analyses identified differentially expressed miRNAs specifically in larvae, with candidate miRNAs screened to predict target genes, particularly those involved in detoxification pathways. A total of 184 known miRNAs and 209 novel miRNAs were identified across stages. Comparative analysis revealed 54, 15, and 18 miRNAs differentially expressed in larvae, compared to egg, pupa, and adult stages, respectively. Eight miRNAs showed significant differential expression across stages, validated by quantitative reverse transcription PCR (qRT-PCR). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses predicted target genes' functions, identifying eight differentially expressed miRNAs targeting 10 gene families associated with detoxification metabolism, including P450s, glutathione S-transferase (GSTs), ATP-binding cassette (ABC) transporters, and sodium channels. These findings elucidate the species-specific miRNA profiles and regulatory mechanisms of detoxification-related genes in S. frugiperda larvae, offering insights and strategies for effectively managing this pest.

A detailed analysis of 16S rRNA gene sequencing and conventional PCR-based testing for the diagnosis of bacterial pathogens and discovery of novel bacteria.

This study represents the first analysis of the bacterial community in chickens affected by swollen head syndrome, utilizing 16S rRNA gene sequencing. Samples were obtained from clinical laying chickens and were examined for the presence of Avibacterium paragallinarum (APG) and Ornithobacterium rhinotracheale (ORT) using conventional polymerase chain reaction (PCR). From the samples, five APG-positive (APG) and APG-negative (N-APG) samples were chosen, along with five specific pathogen-free chickens, for 16S rRNA gene sequencing. Results showed that APG and ORT were widely detected in the chicken samples with swollen head syndrome (SHS, 9/10), while APG was detected in all five specific pathogen-free (SPF) samples. In contrast, conventional PCR sensitivity was found to be inadequate for diagnosis, with only 35.7% (5/14) and 11.1% (1/9) sensitivity for APG and ORT, respectively, based on 16S rRNA gene sequencing data. Furthermore, 16S rRNA gene sequencing was able to quantify the bacteria in the samples, revealing that the relative abundance of APG in the APG group ranged from 2.7 to 81.3%, while the relative abundance of APG in the N-APG group ranged from 0.1 to 21.0%. Notably, a low level of APG was also detected in all 5 SPF samples. The study also identified a significant number of animal and human common bacterial pathogens, including but not limited to Gallibacterium anatis, Riemerella columbina, Enterococcus cecorum, Mycoplasma synoviae, Helicobacter hepaticus, and Staphylococcus lentus. In conclusion, 16S rRNA gene sequencing is a valuable tool for bacterial pathogen diagnosis and the discovery of novel bacterial pathogens, while conventional PCR is not reliable for diagnosis.

Enhancement of anti-PD-L1 antibody plus anlotinib efficacy due to downregulation of PD-L1 in the micro-conduit endothelium within the tumor: a randomized double-blind trial.

OBJECTIVE: The possible enhancing effect of anlotinib on programmed death receptor ligand (PD-L1) antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium, including lymphatic endothelial cells (LECs) and blood endothelial cells (BECs), were determined to identify patients who would benefit from this treatment. METHODS: PD-L1 positivity in LECs, BECs, and tumor cells (TCs) was assessed using paraffin sections with multicolor immunofluorescence in an investigator's brochure clinical trial of TQB2450 (PD-L1 antibody) alone or in combination with anlotinib in patients with non-small cell lung cancer. Progression-free survival (PFS) with different levels of PD-L1 expression was compared between the two groups. RESULTS: Among 75 patients, the median PFS (mPFS) was longer in patients who received TQB2450 with anlotinib [10 and 12 mg (161 and 194 days, respectively)] than patients receiving TQB2450 alone (61 days) [hazard ratio (HR)10 mg = 0.390 (95% confidence interval {CI}, 0.201-0.756), P = 0.005; HR12 mg = 0.397 (0.208-0.756), P = 0.005]. The results were similar among 58 patients with high PD-L1 expression in LECs and TCs [159 and 209 vs. 82 days, HR10 mg = 0.445 (0.210-0.939), P = 0.034; HR12 mg = 0.369 (0.174-0.784), P = 0.009], and 53 patients with high PD-L1 expression in BECs and TCs [161 and 209 vs. 41 days, HR10 mg = 0.340 (0.156-0.742), P = 0.007; HR12 mg = 0.340 (0.159-0.727), P = 0.005]. No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases. CONCLUSIONS: Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs. Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs, which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.

Detection of Dopamine Based on Aptamer-Modified Graphene Microelectrode.

In this paper, a novel aptamer-modified nitrogen-doped graphene microelectrode (Apt-Au-N-RGOF) was fabricated and used to specifically identify and detect dopamine (DA). During the synthetic process, gold nanoparticles were loaded onto the active sites of nitrogen-doped graphene fibers. Then, aptamers were modified on the microelectrode depending on Au-S bonds to prepare Apt-Au-N-RGOF. The prepared microelectrode can specifically identify DA, avoiding interference with other molecules and improving its selectivity. Compared with the N-RGOF microelectrode, the Apt-Au-N-RGOF microelectrode exhibited higher sensitivity, a lower detection limit (0.5 µM), and a wider linear range (1~100 µM) and could be applied in electrochemical analysis fields.

Perception and needs: a qualitative study on sense of job security among nurses in central and western China.

AIMS: To explore nurses' perceptions of sense of job security and their needs to improve it. DESIGN: A descriptive qualitative study employed an in-depth, in-person interview from February to April in 2021. The data analysis software NVivo V.11.0 was used to assist with the data organisation, and content analysis methods were conducted to explore key concepts. SETTING: Three tertiary hospitals in central and western China were selected by convenience sampling method. PARTICIPANTS: A total of 20 nurses participated in this study. RESULTS: Four categories and 13 subcategories were extracted. The four main categories included: (1) enrich connotation of sense of job security; 2) challenges to sense of job security; (3) consequences of a sense of insecurity; and (4) the need to improve nurses' sense of job security. CONCLUSIONS: Nurses expressed a multidimensional perception of a sense of security about the nursing profession, and they highlighted the importance of communication skills training and supervisors' humanistic care and support. It is necessary to improve the training system for nurses' ability improvement, a harmonious work environment, policies and psychological health support to enhance their sense of job security.

[Analysis of the current quality of life status and influencing factors of sepsis survivors in intensive care unit].

OBJECTIVE: To explore the current situation and influencing factors of quality of life of septic patients in intensive care unit (ICU) after discharge, and to provide theoretical basis for clinical early psychological intervention and continuity of care. METHODS: A prospective observational study was conducted. The septic patients who were hospitalized in the department of critical care medicine of the Affiliated Hospital of Jining Medical University and discharged with improvement from January 1 to December 31, 2022 were selected as the research objects. The demographic information, basic diseases, infection site, vital signs at ICU admission, severity scores of the condition within 24 hours after ICU admission, various biochemical indexes, treatment process, and prognostic indexes of all the patients were recorded. All patients were assessed by questionnaire at 3 months of discharge using the 36-item short-form health survey scale (SF-36 scale), the activities of daily living scale (ADL scale), and the Montreal cognitive assessment scale (MoCA scale). Multiple linear regression was used to analyze the factors influencing the quality of life of septic patients after discharge from the hospital. RESULTS: A total of 200 septic patients were discharged with improvement and followed up at 3 months of discharge, of which 150 completed the questionnaire. Of the 150 patients, 57 had sepsis and 93 had septic shock. The total SF-36 scale score of septic patients at 3 months of discharge was 81.4±23.0, and the scores of dimensions were, in descending order, role-emotional (83.4±23.0), mental health (82.9±23.6), bodily pain (82.8±23.3), vitality (81.6±23.2), physical function (81.4±23.5), general health (81.1±23.3), role-physical (79.5±27.0), and social function (78.8±25.2). There was no statistically significant difference in the total SF-36 scale score between the patients with sepsis and septic shock (82.6±22.0 vs. 80.7±23.6, P > 0.05). Incorporating the statistically significant indicators from linear univariate analysis into multiple linear regression analysis, and the results showed that the factors influencing the quality of life of septic patients at 3 months after discharge included ADL scale score at 3 months after discharge [ß= 0.741, 95% confidence interval (95%CI) was 0.606 to 0.791, P < 0.001], length of ICU stay (ß= -0.209, 95%CI was -0.733 to -0.208, P = 0.001), duration of mechanical ventilation (ß= 0.147, 95%CI was 0.122 to 0.978, P = 0.012), total dosage of norepinephrine (ß= -0.111, 95%CI was -0.044 to -0.002, P = 0.028), mean arterial pressure (MAP) at ICU admission (ß= -0.102, 95%CI was -0.203 to -0.007, P = 0.036) and body weight (ß= 0.097, 95%CI was 0.005 to 0.345, P = 0.044). CONCLUSIONS: The quality of life of patients with sepsis at 3 months after discharge is at a moderately high level. The influencing factors of the quality of life of patients with sepsis at 3 months after discharge include the ADL scale score at 3 months after discharge, the length of ICU stay, the duration of mechanical ventilation, the total dosage of norepinephrine, MAP at ICU admission and body weight, and healthcare professionals should enhance the treatment and care of the patients during their hospitalization based on the above influencing factors, and pay attention to early psychological intervention and continued care for such patients.

Surveillance of noise exposure level in industrial enterprises-Jiangsu Province, China, 2022.

Occupational noise exposure is the most prominent problem in industrial enterprises in Jiangsu Province. Since 2019, China has established the National Surveillance System for Occupational Hazards in the workplace to grasp the current occupational hazards in critical industries, including occupational noise. According to the Work Plan for Surveillance of Occupational Hazards in the Workplace (2022) issued by the National Health Commission of the People's Republic of China, the noise exposure level of 3,142 enterprises in our province was monitored, the median and interquartile range (IQR) were calculated, and the distribution of noise exposure level was described by industry classification, enterprise-scale and ownership type of the enterprise. The railway, shipping, aerospace, and other transportation equipment manufacturing industries exhibited the highest proportion (42.9%) of individual noise exposure levels exceeding 85 dB(A), followed by the motor vehicles manufacturing industry (36.4%). The proportion of individual noise exposure levels exceeding 85 dB(A) was higher in medium and small enterprises, with rates of 28.1 and 28.6%, respectively. The highest proportion of personal noise exposure levels exceeding 85 dB(A) was observed in Hong Kong, Macao and Taiwan investment enterprises (37.5%), followed by incorporated companies (34.6%) and limited liability companies (28.1%), the lowest was state-owned enterprises(15.5%). The areas with excessive noise are primarily concentrated in grinding, welding, machining, cutting, and other related operations, accounting for 61.2% of the total. Among these operations, grinding accounts for 29.8%. The highest environmental noise and individual noise intensity were found in sandblasting and grinding positions, with individual noise intensities of 115.5 dB(A) and 108.4 dB(A), respectively. The noise exposure risk is so high that cannot be ignored in the manufacturing industry, especially in Hong Kong, Macao, and Taiwan investment enterprises, incorporated companies and medium and small enterprises.

Professional identity, job satisfaction, and turnover intention among Chinese novice nurses: A cross-sectional study.

The world is faced with challenges due to a growing aging population and the increasing burden of chronic disease. The acute shortage of nurses and high turnover rates, particularly among novice nurses, are of great concern in many countries. Several studies have shown that turnover intention among nurses is influenced by professional identity and job satisfaction. However, to the best of our knowledge, no studies have examined this issue in the context of novice nurses. Thus, the present study aimed to explore the relationship between professional identity, job satisfaction, and turnover intention among novice nurses in China. From March 18 to April 23, 2022, a cross-sectional survey was carried out involving 532 novice nurses recruited from four public hospitals in Sichuan Province, China. Among the sample, 526 questionnaires were retrieved, with an effective response rate of 98.87%. The mean scores for turnover intention, professional identity, and job satisfaction were 13.02 ±â€…3.94, 36.17 ±â€…7.98, and 111.02 ±â€…21.46, respectively. High turnover intention was observed among novice nurses, of whom 54.37% (286/526) had high or very high turnover intention. Professional identity and job satisfaction among novice nurses were moderate. In terms of demographic characteristics, "Whether living with relatives" and "Monthly income" had a statistically significant impact on the turnover intention of novice nurses (P < .05). Both professional identity (r = -0.459) and job satisfaction (r = -0.517) were significantly and moderately negatively correlated with turnover intention (P < .01). The results of the multivariate linear regression analysis revealed that variables including "Whether living with relatives," "Professional identity," "Control and responsibility for work," and "Benefits" jointly accounted for 29.9% of the variance related to turnover intention among novice nurses. "Whether living with relatives," "Professional identity," "Control and responsibility for work," and "Benefits" were highly predictive of turnover intention levels among novice nurses. Hence, potential predictors of turnover intention should be considered, and intervention research should be conducted to reduce the level of turnover intention among novice nurses.

Integrated metabolome and transcriptome analyses of anthocyanin biosynthesis reveal key candidate genes involved in colour variation of Scutellaria baicalensis flowers.

BACKGROUND: Bright flower colour assists plants attract insects to complete pollination and provides distinct ornamental values. In some medicinal plants, diverse flower colour variations usually imply differences in active ingredients. Compared to the common bluish purple of Scutellaria baicalensis flower (SB), the natural variants present rose red (SR) and white (SW) flowers were screened out under the same growing conditions in the genuine producing area Shandong Province, China. However, the mechanism of flower colour variation in S. baicalensis was remain unclear. In the present study, we conducted integrated transcriptome and metabolome analyses to uncover the metabolic difference and regulation mechanism in three S. baicalensis flowers. RESULTS: The results showed that 9 anthocyanins were identified. Among which, 4 delphinidin-based anthocyanins were only detected in SB, 4 cyanidin-based anthocyanins (without cyanidin-3-O-glucoside) mainly accumulated in SR, and no anthocyanin but high level of flavanone, naringenin, was detected in SW. The gene expression profile indicated that the key structural genes in the flavonoid and anthocyanin biosynthesis pathway differentially expressed in flowers with different colours. Compared to SB, the down-regulated expression of F3'5'H, ANS, and 3GT gene in SR might influence the anthocyanin composition. Especially the InDel site with deletion of 7 nucleotides (AATAGAG) in F3'5'H in SR might be the determinant for lack of delphinidin-based anthocyanins in rose red flowers. In SW, the lower expression levels of DFR and two F3H genes might reduce the anthocyanin accumulation. Notably the SNP site of G > A mutation in the splicing site of DFR in SW might block anthocyanin biosynthesis from flavanones and thus cause white flowers. In addition, several key transcription factors, including MYB, bHLH, and NAC, which highly correlated with structural gene expression and anthocyanin contents were also identified. CONCLUSIONS: These results provide clues to uncover the molecular regulatory mechanism of flower colour variation in S. baicalensis and promote novel insights into understanding the anthocyanin biosynthesis and regulation.

A randomized double-blind trial of TQB2450 with or without anlotinib in pretreated driver-negative non-small cell lung cancer.

OBJECTIVE: Immune monotherapy as second-line treatment confers only modest survival benefit on non-small cell lung cancer (NSCLC) patients with no mutated driver genes, necessitating combination treatment strategies. This phase Ib trial investigated the efficacy and safety of anti-PD-L1 antibody TQB2450 plus antiangiogenic drug anlotinib for NSCLC. MATERIALS AND METHODS: Pretreated stage IIIB or IV NSCLC patients with wild-type EGFR/ALK and minimally one measurable lesion were randomized 1:1:1 to receive TQB2450 1200 mg plus placebo, or TQB2450 1200 mg plus anlotinib 10 or 12 mg. The primary outcome was progression-free survival (PFS) and the secondary outcomes included objective response rate (ORR). RESULTS: Thirty-three patients received TQB2450 plus placebo and 34 patients each received TQB2450 plus anlotinib 10 mg and 12 mg. At the data cutoff, the median PFS was 8.7 months (95% CI 6.1-17.1) in the TQB2450 plus anlotinib group and 2.8 months (95% CI 1.4-4.7) in the TQB2450 only group. The ORR reached 30.9% (95% CI 20.2%-43.3%) in the TQB2450 plus anlotinib group and was 3.0% (95% CI 0.1%-15.8%) in the TQB2450 only group. In patients with PD-L1 ≥ 1%, the ORR was 50.0% (95% CI 33.4%-66.6%) for TQB2450 plus anlotinib and 5.3% (95% CI 0.1%-26.0%) for TQB2450 plus placebo. No new safety signals were observed. CONCLUSION: Anlotinib plus TQB2450 demonstrated promising antitumor activities in advanced NSCLC patients without EGFR and ALK alterations and the toxicities were overall manageable. The study findings support the continued development of TQB2450 plus anlotinib for advanced NSCLC patients without driver gene alterations.

Integrated metabolic profiling and transcriptome analysis of Lonicera japonica flowers for chlorogenic acid, luteolin and endogenous hormone syntheses.

The active ingredients of many medicinal plants are the secondary metabolites associated with the growth period. Lonicera japonica Thunb. is an important traditional Chinese medicine, and the flower development stage is an important factor that influences the quality of medicinal ingredients. In this study, transcriptomics and metabolomics were performed to reveal the regulatory mechanism of secondary metabolites during flowering of L. japonica. The results showed that the content of chlorogenic acid (CGA) and luteolin gradually decreased from green bud stage (Sa) to white flower stage (Sc), especially from white flower bud stage (Sb) to Sc. Most of the genes encoding the crucial rate-limiting enzymes, including PAL, C4H, HCT, C3'H, F3'H and FNSII, were down-regulated in three comparisons. Correlation analysis identified some members of the MYB, AP2/ERF, bHLH and NAC transcription factor families that are closely related to CGA and luteolin biosynthesis. Furthermore, differentially expressed genes (DEGs) involved in hormone biosynthesis, signalling pathways and flowering process were analysed in three flower developmental stage.

Association between neutrophil percentage-to-albumin ratio and 28-day mortality in Chinese patients with sepsis.

OBJECTIVE: To assess the association between neutrophil percentage-to-albumin ratio (NPAR) and 28-day mortality in severely ill Chinese patients with sepsis. METHODS: In this retrospective, single-centre study, sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University between May 2015 and December 2021 were retrospectively analysed. The relationship between NPAR and 28-day mortality was examined using Cox proportional-hazards model. RESULTS: In total, 741 patients with sepsis were included. Multivariate analysis, adjusted for age, sex, body mass index (BMI), smoking and alcohol drinking history, showed an association between elevated NPAR and a high risk of 28-day mortality. After removal of additional confounders, moderate and high NPAR values remained significantly associated with 28-day mortality in comparison with low NPAR values (tertile 2 vs 1: HR, 95% CI: 1.42, 1.06-1.90; tertile 3 vs 1: HR, 95% CI: 1.35, 1.00-1.82). Survival curves stratified by NPAR groups showed that high NPAR levels had lower survival probabilities than lower NPAR levels. Subgroup analysis did not show any significant interactions between NPAR and 28-day mortality. CONCLUSIONS: Elevated NPAR values were linked to increased 28-day mortality in severely ill Chinese patients with sepsis. The findings require verification by large, prospective, multi-centre studies.

The response prediction and prognostic values of systemic inflammation response index in patients with advanced lung adenocarcinoma.

PURPOSE: This study aimed to assess the response prediction and prognostic values of different peripheral blood cell biomarkers for advanced lung adenocarcinoma (LUAD) patients receiving first-line therapy. METHODS: Patients diagnosed with advanced LUAD as well as healthy controls and patients with benign pulmonary diseases were collected in this retrospective study. Propensity score matching (PSM) was performed in a 1:1 ratio. Survival state was estimated by the Kaplan-Meier method and the Cox proportional hazard model was used to assess the prognostic factors. RESULTS: Compared with the control groups, the level of peripheral blood leucocyte, neutrophil, monocyte, platelet, and neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, platelet to lymphocyte ratio, and systemic inflammation response index (SIRI) were higher in LUAD patients (all p < 0.001). Some inflammatory markers decreased at the time of optimal response and then increased again as the disease progressed. Multivariate analysis revealed that SIRI and lactate dehydrogenase (LDH) were independent prognostic factors no matter before or after PSM analysis. Area under the curve (AUC) of SIRI and LDH were 0.625 (p < 0.001) and 0.596 (p = 0.008), respectively. When SIRI and LDH were combined, the AUC reached 0.649 (p < 0.001). CONCLUSIONS: Pretreatment SIRI was an independent prognostic factor of progression free survival (PFS) in advanced LUAD patients. Dynamic monitoring of inflammatory index changes could help to predict therapeutic efficacy. The combination of SIRI and LDH is expected to be a promising clinically accessible biomarker in the future.

Nanostructured ionic hydrogel with integrated conductivity, stretchability and thermal responsiveness for a high-performance strain and temperature sensor.

Ionic conductive hydrogels are promising candidates for fabricating wearable sensors for human motion detection and disease diagnosis, and electronic skin. However, most of the existing ionic conductive hydrogel-based sensors primarily respond to a single-strain stimulus. Only a few ionic conductive hydrogels can respond to multiple physiological signals. Although some studies have explored multi-stimulus sensors, such as those detecting strain and temperature, the ability to identify the type of stimulus remains a challenge, which limits their applications. Herein, a multi-responsive nanostructured ionic conductive hydrogel was successfully developed by crosslinking the thermally sensitive poly(N-isopropylacrylamide-co-ionic liquid) conductive nanogel (PNI NG) with a poly(sulfobetaine methacrylate-co-ionic liquid) (PSI) network. The resultant hydrogel (PNI NG@PSI) was endowed with good mechanical stretchability (300%), resilience and fatigue resistance, and excellent conductivity (2.4 S m-1). Furthermore, the hydrogel exhibited a sensitive and stable electrical signal response and has a potential application in human motion detection. Moreover, the introduction of a nanostructured thermally responsive PNIPAAm network also endowed it with a sensitive and unique thermal-sensing ability to timely and accurately record temperature changes in the range of 30-45 °C, holding promise for application as a wearable temperature sensor to detect fever or inflammation in the human body. In particular, as a dual strain-temperature sensor, the hydrogel demonstrated an excellent capability of distinguishing the type of stimulus from superposed strain-temperature stimuli via electrical signals. Therefore, the implementation of the proposed hydrogel in wearable multi-signal sensors provides a new strategy for different applications, such as health monitoring and human-machine interactions.

The Adaptive Evolution in the Fall Armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae) Revealed by the Diversity of Larval Gut Bacteria.

Insect gut microbes have important roles in host feeding, digestion, immunity, development, and coevolution with pests. The fall armyworm, Spodoptera frugiperda (Smith, 1797), is a major migratory agricultural pest worldwide. The effects of host plant on the pest's gut bacteria remain to be investigated to better understand their coevolution. In this study, differences in the gut bacterial communities were examined for the fifth and sixth instar larvae of S. frugiperda fed on leaves of different host plants (corn, sorghum, highland barley, and citrus). The 16S rDNA full-length amplification and sequencing method was used to determine the abundance and diversity of gut bacteria in larval intestines. The highest richness and diversity of gut bacteria were in corn-fed fifth instar larvae, whereas in sixth instar larvae, the richness and diversity were higher when larvae were fed by other crops. Firmicutes and Proteobacteria were dominant phyla in gut bacterial communities of fifth and sixth instar larvae. According to the LDA Effect Size (LEfSe) analysis, the host plants had important effects on the structure of gut bacterial communities in S. frugiperda. In the PICRUSt2 analysis, most predicted functional categories were associated with metabolism. Thus, the host plant species attacked by S. frugiperda larvae can affect their gut bacterial communities, and such changes are likely important in the adaptive evolution of S. frugiperda to host plants.