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Abstract Peritoneal recurrence (PR) in gastric cancer after curative resection has poor prognosis. Therefore, we aimed to construct a nomogram to predict PR, and establish PR score for risk stratification to guide adjuvant chemotherapy. A total of 315 patients with gastric cancer after radical surgery were included, and randomly stratified into training group (n = 221) and validation group (n = 94). Univariate and multivariate analyses were used to determine predictive factors of PR. The nomogram was constructed to predict the risk of PR. We utilized the time-dependent area under the receiver operating characteristic (ROC) curves (AUCs), calibration curves, and decision curve analysis (DCA) to evaluate the performance of the nomogram. Multivariate analysis showed that tumor site, N stage, preoperative CEA, and postoperative CA199 were independent predictors of PR. A nomogram was constructed to predict PR based on these factors. The AUC value was 0.755 in the training group and 0.715 in the validation group. The calibration curves showed good agreement between prediction and observation in the training and validation groups. The decision curve analysis displayed a good net benefit of the nomogram. The novel PR score was developed and patients were stratified into the low-, medium-, and high -risk groups. For the high-risk group, postoperative adjuvant chemotherapy significantly improved patients' overall survival (OS) and disease-free survival (DFS). The establishment of nomogram facilitates the prediction of PR after radical gastrectomy, and a novel PR score may help guide adjuvant chemotherapy for gastric cancer.

Abstract Background Acute monocytic leukemia-M5 (AML-M5) remains a challenging disease due to its high morbidity and poor prognosis. In addition to the evidence mentioned earlier, several studies have shown that programmed cell death (PCD) serves a critical function in treatment of AML-M5. However, the role and relationship between ferroptosis and necroptosis in AML-M5 remains unclear. Methods THP-1 cells were mainly treated with Erastin and IMP-366. The changes of ferroptosis and necroptosis levels were detected by CCK-8, western blot, quantitative real-time PCR, and electron microscopy. Flow cytometry was applied to detect the ROS and lipid ROS levels. MDA, 4-HNE, GSH and GSSG were assessed by ELISA kits. Intracellular distribution of FSP1 was studied by immunofluorescent staining and western blot. Results The addition of the myristoylation inhibitor IMP-366 to erastin-treated acute monocytic leukemia cell line THP-1 cell not only resulted in greater susceptibility to ferroptosis characterized by lipid peroxidation, glutathione (GSH) depletion and mitochondrial shrinkage, as the FSP1 position on membrane was inhibited, but also increased p-RIPK1 and p-MLKL protein expression, as well as a decrease in caspase-8 expression, and triggered the characteristic necroptosis phenomena, including cytoplasmic translucency, mitochondrial swelling, membranous fractures by FSP1 migration into the nucleus via binding importin α2. It is interesting to note that ferroptosis inhibitor fer-1 reversed necroptosis. Conclusion We demonstrated that inhibition of myristoylation by IMP-366 is capable of switching ferroptosis and ferroptosis-dependent necroptosis in THP-1 cells. In these findings, FSP1-mediated ferroptosis and necroptosis are described as alternative mechanisms of PCD of THP-1 cells, providing potential therapeutic strategies and targets for AML-M5.

Abstract Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3–36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9–7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002–1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056–2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.

ObjectiveThis study aimed to develop and validate a survival prediction model and nomogram to predict survival in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma undergoing treatment with anti-programmed cell death 1 receptor (PD-1). This model incorporates immune-related adverse events (irAEs) alongside common clinical characteristics as predictive factors.MethodA dataset comprising 255 adult patients diagnosed with advanced G/GEJ adenocarcinoma was assembled. The irAEs affecting overall survival (OS) to a significant degree were identified and integrated as a candidate variable, together with 12 other candidate variables. These included gender, age, Eastern cooperative oncology group performance status (ECOG PS) score, tumor stage, human epidermal growth factor receptor 2 (HER2) expression status, presence of peritoneal and liver metastases, year and line of anti-PD-1 treatment, neutrophil-to-lymphocyte ratio (NLR), controlling nutritional status (CONUT) score, and Charlson comorbidity index (CCI). To mitigate timing bias related to irAEs, landmark analysis was employed. Variable selection was performed using the least absolute shrinkage and selection operator (LASSO) regression to pinpoint significant predictors, and the variance inflation factor was applied to address multicollinearity. Subsequently, a Cox regression analysis utilizing the forward likelihood ratio method was conducted to develop a survival prediction model, excluding variables that failed to satisfy the proportional hazards (PH) assumption. The model was developed using the entire dataset, then internally validated through bootstrap resampling and externally validated with a cohort from another Hospital. Furthermore, a nomogram was created to delineate the predictive model.ResultsAfter consolidating irAEs from the skin and endocrine systems into a single protective irAE category and applying landmark analysis, variable selection was conducted for the prognostic prediction model along with other candidate variables. The finalized model comprised seven variables: ECOG PS score, tumor stage, HER2 expression status in tumor tissue, first-line anti-PD-1 treatment, peritoneal metastasis, CONUT score, and protective irAE. The overall concordance index for the model was 0.66. Calibration analysis verified the model’s accuracy in aligning predicted outcomes with actual results. Clinical decision curve analysis indicated that utilizing this model for treatment decisions could enhance the net benefit regarding 1- and 2-year survival rates for patients.ConclusionThis study developed a prognostic prediction model by integrating common clinical characteristics of irAEs and G/GEJ adenocarcinoma. This model exhibits good clinical practicality and possesses accurate predictive ability for overall survival OS in patients with advanced G/GEJ adenocarcinoma.

BackgroundTo investigate the effectiveness and safety of maintenance regimens based on cetuximab, we conducted a real-world, single-arm, retrospective study at a single center.MethodsIn Fujian Medical University Union Hospital, patients with unresectable metastatic colorectal cancer (mCRC) who received cetuximab-based maintenance therapy between December 2020 and December 2021 were included. All patients had RAS and BRAF wild-type. The maintenance regimen consisted of 6–12 cycles of cetuximab plus irinotecan (Phase 1) and cetuximab (Phase 2). Patients could receive reintroduction therapy in case of disease progression during Phase 2. Progression-free survival (PFS), overall survival (OS), and safety data were collected.ResultsAccording to the inclusion and exclusion criteria of the study, a total of 108 subjects who received maintenance therapy were included— 51 experienced disease progression during Phase 1, with PFS (1) of 7.3 months. Among the 52 patients who entered Phase 2, 17 were still in this phase at the end of follow-up, with PFS (2) of 10.1 months. In Phase 2, 35 patients experienced disease progression, of whom 24 received reintroduction therapy, with PFS (3) of 6.7 months. The overall PFS (total) during the maintenance period was 11.9 months, and the OS was 39.2 months. Grade III or higher adverse events were 4.6% during Phase 1 and 0% during Phase 2.ConclusionInnovative cetuximab-based maintenance therapy showed a trend toward improving the prognosis of mCRC patients with RAS and BRAF wild-type, while the toxic side effects of maintenance therapy were manageable.Clinical trial registrationhttps://www.chictr.org.cn, identifier ChiCTR2000040940.

Cannabinoid CB2 agonists show therapeutic efficacy without unwanted CB1-mediated side effects. The G protein-biased CB2 receptor agonist LY2828360 attenuates the maintenance of chemotherapy-induced neuropathic nociception in male mice and blocks development of morphine tolerance in this model. However, the cell types involved in this phenomenon are unknown and whether this therapeutic profile is observed in female mice has never been investigated. We used conditional deletion of CB2 receptors to determine the cell population(s) mediating the anti-allodynic and morphine-sparing effects of CB2 agonists. Anti-allodynic effects of structurally distinct CB2 agonists (LY2828360 and AM1710) were present in paclitaxel-treated CB2f/f mice and in mice lacking CB2 receptors in CX3CR1 expressing microglia/macrophages (CX3CR1CRE/+; CB2f/f), but were absent in mice lacking CB2 receptors in peripheral sensory neurons (AdvillinCRE/+; CB2f/f). The morphine-sparing effect of LY28282360 occurred in a sexually-dimorphic manner, being present in male, but not female, mice. LY2828360 treatment (3 mg/kg per day i.p. x 12 days) blocked the development of morphine tolerance in male CB2f/f and CX3CR1CRE/+; CB2f/f mice with established paclitaxel-induced neuropathy but was absent in male (or female) AdvillinCRE/+; CB2f/f mice. Co-administration of morphine with a low dose of LY2828360 (0.1 mg/kg per day i.p. x 6 days) reversed morphine tolerance in paclitaxel-treated male CB2f/f mice, but not AdvillinCRE/+; CB2f/f mice of either sex. LY2828360 (3 mg/kg per day i.p. x 8 days) delayed, but did not prevent, the development of paclitaxel-induced mechanical or cold allodynia in either CB2f/f or CX3CR1CRE/+; CB2f/f mice of either sex. Our findings have potential clinical implications.

Abstract Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.

Introduction: Acute respiratory distress syndrome (ARDS) is a leading cause of respiratory failure, with substantial attributable morbidity and mortality. The small animal models that are currently used for ARDS do not fully manifest all of the pathological hallmarks of human patients, which hampers both the studies of disease mechanism and drug development. Objectives: To examine whether the phenotypic changes of primate-like tree shrews in response to a one-hit lipopolysaccharides (LPS) injury resemble human ARDS features. Methods: LPS was administered to tree shrews through intratracheal instillation; then, the animals underwent CT or PET/CT imaging to examine the changes in the structure and function of the whole lung. The lung histology was analyzed by H&E staining and immunohistochemical staining of inflammatory cells. Results: Results demonstrated that tree shrews exhibited an average survival time of 3–5 days after LPS insult, as well as an obvious symptom of dyspnea before death. The ratios of PaO2 to FiO2 (P/F ratio) were close to those of moderate ARDS in humans. CT imaging showed that the scope of the lung injury in tree shrews after LPS treatment were extensive. PET/CT imaging with 18F-FDG displayed an obvious inflammatory infiltration. Histological analysis detected the formation of a hyaline membrane, which is usually present in human ARDS. Conclusion: This study established a lung injury model with a primate-like small animal model and confirmed that they have similar features to human ARDS, which might provide a valuable tool for translational research.

Abstract Purpose This investigation sought to examine the efficacy and safety of low-dose apatinib used alongside chemotherapy in the clinical management of patients with metastatic triple-negative breast cancer (TNBC) within a real-world setting, whilst comparing the outcomes with those treated solely with chemotherapy. Methods This case series study analyzed clinical data and treatment outcomes of 163 patients with metastatic TNBC who underwent rescue treatment at the Medical Oncology Department of Clinical Oncology, Fujian Cancer Hospital, School of Fujian Medical University, China, between October 2011 and January 2023. All the patients underwent rescue treatment with either chemotherapy alone or apatinib (250 mg/day) combined with chemotherapy. The study’s primary outcome was progression-free survival (PFS), whereas the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles. Results The study was designed to compare two groups [1]. Out of the 163 TNBC patients who participated in the study, 107 individuals (65.6%) received treatment based on chemotherapy, whereas 56 patients (34.4%) were given treatment based on a combination of low-dose apatinib (250 mg/day) and other treatments, including chemotherapy. After propensity score matching (PSM), the objective response rate (ORR) and disease control rate (DCR) of patients with advanced triple-negative breast cancer (TNBC) who received apatinib-based treatment were 50.0 and 90.0%, respectively, while they were 6.7 and 20.0%, respectively, for the chemotherapy-based group (P

AbstractObjective To assess the impact of low-dose aspirin (LDA) on obstetrical outcomes through a meta-analysis of placebo-controlled randomized controlled trials (RCTs).Methods A systematic search of the PubMed, Cochrane Library, Web of Science and Embase databases from inception to January 2024 was conducted to identify studies exploring the role of aspirin on pregnancy, reporting obstetrical-related outcomes, including preterm birth (PTB, gestational age 20 weeks).Results Forty-seven studies involving 59,124 participants were included. Compared with placebo, LDA had a more significant effect on low-risk events such as SGA, PTB and LBW. Specifically, LDA significantly reduced the risk of SGA (RR = 0.91, 95% CI: 0.87–0.95), PTB (RR = 0.93, 95% CI: 0.89–0.97) and LBW (RR = 0.94, 95% CI: 0.89–0.99). For high-risk events, LDA significantly lowered the risk of NICU admission (RR = 0.93, 95% CI: 0.87–0.99). On the other hand, LDA can significantly increase the risk of placental abruption (RR = 1.72, 95% CI: 1.23–2.43). Subgroup analyses showed that LDA significantly reduced the risk of SGA (RR = 0.86, 95% CI: 0.77–0.97), PTB (RR = 0.93, 95% CI: 0.88–0.98) and PND (RR = 0.65, 95% CI: 0.48–0.88) in pregnant women at high risk of PE, whereas in healthy pregnant women LDA did not significantly improve obstetrical outcomes, but instead significantly increased the risk of placental abruption (RR = 5.56, 95% CI: 1.92–16.11). In pregnant women at high risk of PE, LDA administered at doses ≥100 mg significantly reduced the risk of SGA (RR = 0.77, 95% CI: 0.66–0.91) and PTB (RR = 0.56, 95% CI: 0.32–0.97), but did not have a statistically significant effect on reducing the risk of NICU, PND and LBW. LDA started at ≤20 weeks significantly reduced the risk of SGA (RR = 0.76, 95% CI: 0.65–0.89) and PTB (RR = 0.56, 95% CI: 0.32–0.97).Conclusions To sum up, LDA significantly improved neonatal outcomes in pregnant women at high risk of PE without elevating the risk of placental abruption. These findings support LDA’s clinical application in pregnant women, although further research is needed to refine dosage and timing recommendations.

Cardiac tumors are uncommon and most of them are benign. Although cases of malignant cardiac tumors are rare, it is still necessary to improve awareness in both clinical and pathological diagnosis. Since cardiac tumors often have a high degree of malignancy, it is vital to determine what form of intervention can increase recurrence-free survival and overall survival. In this paper, we report on a 42-year-old woman in the third trimester of pregnancy who had a cardiac undifferentiated pleomorphic sarcoma. According to her medical history, the patient had never had a cardiac tumor or any other disease. She was treated surgically and a left atrial mass was removed immediately after cesarean section. No other treatments were applied after the surgery, and, unfortunately, the tumor reoccurred 6 months later. We reviewed some literature and found one case in which the patient was treated using radiotherapy and survived for another 2 years after the third tumor recurrence. This suggests that neoadjuvant therapy effectively improves the survival rates of such patients.

Abstract 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.

Abstract Aims Left ventricular remodelling subsequent to myocardial infarction (MI) constitutes a pivotal underlying cause of heart failure. Intervention with the nontoxic endogenous aryl hydrocarbon receptor (AHR) agonist 2‐(1′H‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylic acid methyl ester (ITE) in the acute phase of MI has been shown to ameliorate cardiac function, but its role in the chronic phase remains obscured. This study explores the beneficial role of ITE in delaying the progression of heart failure in the chronic phase of MI. Methods and results MI rats established by ligating the left anterior descending coronary artery were treated with the indicated concentration of the AHR agonist ITE or vehicle alone. Echocardiography was performed to determine cardiac structure and function; myocardial morphology and fibrosis were observed by haematoxylin and eosin and Masson's trichrome staining; serum biochemical indices, BNP, and inflammatory cytokine levels were detected by enzyme‐linked immunosorbent assay; F4/80+iNOS+M1 macrophages and F4/80+CD206+M2 macrophages were detected by immunofluorescence; the terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling assay was used to detect the apoptosis of cardiomyocytes; ultrastructural changes in myocardial tissue were observed by transmission electron microscopy; and Cyp1a1, Akt, P‐Akt, p70S6K, P‐p70S6K, Bcl‐2, Bax, caspase‐3, and cleaved caspase‐3 protein levels were determined via Western blotting. We found that therapy with the AHR agonist ITE rescued cardiac remodelling and dysfunction in rats with MI and attenuated myocardial fibrosis, inflammation, and mitochondrial damage. Further studies confirmed that ITE dose‐dependently improved myocardial cell apoptosis after MI, as demonstrated by reduced levels of the apoptosis‐related proteins cleaved caspase‐3 and Bax but increased expression levels of Bcl‐2. These effects were attributed to ITE‐induced activation of AHR receptors, leading to the down‐regulation of Akt and p70S6K phosphorylation. Conclusions The AHR agonist ITE alleviates cardiomyocyte apoptosis through the Akt/p70S6K signalling pathway, thereby rescuing left ventricular adverse remodelling and cardiac dysfunction after MI.

Fungal contamination in rice and mycotoxins present significant challenges to both rice quality and food safety. However, there is a dearth of comprehensive research on the compositional and structural changes within fungal colonies in rice, particularly in typical rice-producing regions, as well as their underlying influencing factors. In this study, a comprehensive analysis of fungal taxa in rice grains was conducted using amplicon sequencing and bioinformatics methods on 99 rice samples collected in three major rice-producing regions in China: Northeast Plain (NP), Yangtze River Basin (YR), and Southeast Coastal Area (SC). A total of 6,019,722 fungal ITS sequences were obtained with an average sequence length of 235 base pairs, and effective ASVs (2014) accounted for approximately 97.58% of the total ASVs (2064). The fungal community diversity in rice grains exhibited significant variations across the three regions, with deterministic processes playing a predominant role in shaping the ecological dynamics of fungal taxa. Among the core microbiota (92 shared ASVs), the first five species (Alternaria, Fusarium, Curvularia, Epicoccum, and Ustilaginoidea) accounting for a proportion greater than 5% had been reported as potential pathogens for plants. Geographical variations in fungal community composition were evident, with a significantly higher number of shared populations observed between YR and CS regions compared to those in the NP region. Nutrient elements and climatic conditions were the internal and external driving factors of rice fungal community composition. Additionally, notable regional variations in fungal functionality were observed. The findings have significant implications for gaining a comprehensive understanding of the distribution patterns of fungal communities in the major rice-producing regions in China. Additionally, it provides valuable insights into controlling key influencing factors to effectively reduce the occurrence of toxin-producing fungi and mitigate the associated risks related to mycotoxin contamination, thereby contributing to improved risk management and assessment.

Abstract 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.

Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC.Method: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study’s primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria.Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n = 45) and platinum-based therapy (n = 51). The follow-up period for all patients ended on 31 December 2022, and the median follow-up time was 18.3 months (range:0.7–27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median progression-free survival compared to platinum-based (hazard ratio (HR) = 0.41, p = 0.006), nab-paclitaxel-based (hazard ratio = 0.36, p = 0.001) and other chemotherapy (HR = 0.39, p < 0.001). Also, eribulin induced a remarkable prolongation of the median overall survival duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups.Conclusion: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted.

Abstract Background Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings. Methods Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan–Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method. Results Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6–5.4%), and DCR was 35.8% (95% CI, 33.7–38.0%). The median PFS was 2.7 months (95% CI 2.2–2.8), and the median OS was 5.8 months (95% CI 5.4–6.1). Conclusions The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment. Trial registration This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.

Isoetes orientalis is an endangered hexaploidy species of Isoetaceae in China and the complete chloroplast genome of this species has not been reported. In the present study, a complete chloroplast genome of Isoetes orientalis (Isoetaceae) was assembled and annotated. This chloroplast genome has a circular structure of 145,504 bp in length, comprising a pair of inverted repeat (IR) regions of 13,207 bp each, a large single-copy (LSC) region of 91,864 bp, and a small single-copy (SSC) region of 27,226 bp. The chloroplast genome contains 136 genes, including 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis showed that I. orientalis was closely related to I. sinensis. These results provide additional resources for future studies on Isoetes from China and across the globe.

Abstract Background Although programmed cell death 1 (PD‐1) blockade plus chemotherapy can significantly prolong the progression‐free survival (PFS) and overall survival (OS) in first‐line settings in patients with driver‐negative advanced non‐small‐cell lung cancer (NSCLC), the predictive biomarkers remain undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD‐1 blockade plus chemotherapy. Methods Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone. Tumor immune microenvironmental markers, including PD‐1 ligand (PD‐L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan‐Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations. Results Responders had significantly higher CD8/PD‐L1 (P = 0.015) or CD68/PD‐L1 co‐expression levels (P = 0.021) than non‐responders in the camrelizumab plus chemotherapy group, while no difference was observed in the chemotherapy group. Patients with high CD8/PD‐L1 or CD68/PD‐L1 co‐expression level was associated with significantly longer PFS (P = 0.002, P = 0.024; respectively) and OS (P = 0.006, P = 0.026; respectively) than those with low co‐expression in camrelizumab plus chemotherapy group. When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD‐L1 co‐expression stratification, significantly better PFS (P = 0.003) and OS (P = 0.032) were observed in high co‐expression subgroups. The predictive value of CD8/PD‐L1 and CD68/PD‐L1 co‐expression remained statistically significant for PFS and OS when adjusting clinicopathological features. Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD‐L1 or CD68/PD‐L1 co‐expression, the positive groups had a significantly higher proportion of TP53/KRAS co‐mutations than the negative groups (both 13.0% vs. 0.0%, P = 0.023). Notably, enriched PI3K (P = 0.012) and cell cycle pathway (P = 0.021) were found in the CD8/PD‐L1 co‐expression group. Conclusion Tumor immune microenvironmental marker expression, especially CD8/PD‐L1 or CD68/PD‐L1 co‐expression, was associated with the efficacy of PD‐1 blockade plus chemotherapy as first‐line treatment in patients with advanced NSCLC.

Abstract Background Shenling Baizhu Powder (SBP) is a traditional Chinese medicine (TCM) prescription, which has the good efficacy on gastrointestinal toxicity. In this study, we used gut microbiota analysis, metabonomics and network pharmacology to investigate the therapeutic effect of SBP on pyrotinib-induced diarrhea. Methods 24 Rats were randomly divided into 4 groups: control group, SBP group (3.6 g/kg /bid SBP for 10 days), pyrotinib model group (80 mg/kg/qd pyrotinib) and pyrotinib + SBP treatment group. A 16S rRNA sequencing was used to detect the microbiome of rat fecal bowel. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 5.0. The antitumor effect of SBP on cells treated with pyrotinib was measured using a CCK-8 assay. Network pharmacology was used to predict the target and action pathway of SBP in treating pyrotinib-related diarrhea. Results In vivo study indicated that SBP could significantly alleviate pyrotinib-induced diarrhea, reaching a therapeutic effect of 66.7%. SBP could regulate pyrotinib-induced microbiota disorder. LEfSe research revealed that the SBP could potentially decrease the relative abundance of Escherichia, Helicobacter and Enterobacteriaceae and increase the relative abundance of Lachnospiraceae, Bacilli, Lactobacillales etc. In addition, 25-Hydroxycholesterol, Guanidinosuccinic acid, 5-Hydroxyindolepyruvate and cAMP were selected as potential biomarkers of SBP for pyrotinib-induced diarrhea. Moreover, Spearman's analysis showed a correlation between gut microbiota and metabolite: the decreased 25-hydroxycholesterol in the pyrotinib + SBP treatment group was negatively correlated with Lachnospiraceae while positively correlated with Escherichia and Helicobacter. Meanwhile, SBP did not affect the inhibitory effect of pyrotinib on BT-474 cells and Calu-3 cells in vitro. Also, the network analysis further revealed that SBP treated pyrotinib-induced diarrhea through multiple pathways, including inflammatory bowel disease, IL-17 signaling pathway, pathogenic Escherichia coli infection and cAMP signaling pathway. Conclusions SBP could effectively relieve pyrotinib-induced diarrhea, revealing that intestinal flora and its metabolites may be involved in this process.

Pectin degradation in the cell walls and middle lamella greatly affects the texture and the quality of the fruit including the taste and storage time. This directly affects its acceptability, supply to the consumer market, and economic benefits. It is therefore essential to establish the relationship between the chemical changes of pectin and the texture of the fruit to improve its preservation. This study was designed to evaluate the degradation of pectin in the peels of Tarocco blood orange and the textural changes during postharvest storage and further investigate their relationship over the study period. The texture of the fruit was characterized using the texture profile analyzer and the degradation of pectin was investigated by testing the content of the pectin, degree of esterification, and galacturonic acid content. The physicochemical properties, such as weight loss, moisture content, and anthocyanin content were also measured. Furthermore, the structural changes of the pectin were analyzed by molecular weight determination and FTIR test. The results showed that the Mw of pectin decreased from 568.05 kDa to 362.55 kDa, with a 42.1% decline in pectin content for storing for 63 d. The gradual solubilization, depolymerization, and de-esterification of the pectin consequently led to the decline in the textual properties of the fruit during postharvest storage. This can be applied and lead to improvements in quality control and process design in the food industry and the marketplace for the fruit during storage and preservation.

The effect of the application of copper waterline on the performance and gut health of aged laying hens was evaluated in this study. Forty-eight 70-week-old laying hens were divided into two groups (three replicates of eight hens each): control and copper (Cu) groups provided with normal polyvinyl chloride (PVC) waterline or Cu waterline. The laying performance was measured during the four-week period of the experiment. The intestinal antioxidant status and the microbiota diversity of the cecal content were determined. Moreover, a bacteriostasis test on Escherichia coli and Salmonella enteritidis was conducted after inoculation in waterline and hens, respectively. The water Cu2+ content was increased by Cu waterline compared to the control (P

Parkinson’s disease (PD), the second most common neurodegenerative disease worldwide, often occurs in middle-aged and elderly individuals. The pathogenesis of PD is complex and includes mitochondrial dysfunction, and oxidative stress. Recently, natural products with multiple structures and their bioactive components have become one of the most important resources for small molecule PD drug research targeting mitochondrial dysfunction. Multiple lines of studies have proven that natural products display ameliorative benefits in PD treatment by regulating mitochondrial dysfunction. Therefore, a comprehensive search of recent published articles between 2012 and 2022 in PubMed, Web of Science, Elesvier, Wliey and Springer was carried out, focusing on original publications related to natural products against PD by restoring mitochondrial dysfunction. This paper presented the mechanisms of various kinds of natural products on PD-related mitochondrial dysfunction regulation and provided evidence that natural products are promising to be developed as drugs for PD therapeutics.

Panel count data often occur in a long-term recurrent event study, where the exact occurrence time of the recurrent events is unknown, but only the occurrence count between any two adjacent observation time points is recorded. Most traditional methods only handle panel count data for a single type of event. In this paper, we propose a Bayesian semiparameteric approach to analyze panel count data for multiple types of events. For each type of recurrent event, the proportional mean model is adopted to model the mean count of the event, where its baseline mean function is approximated by monotone I-splines. The correlation between multiple types of events is modeled by common frailty terms and scale parameters. Unlike many frequentist estimating equation methods, our approach is based on the observed likelihood and makes no assumption on the relationship between the recurrent process and the observation process. Under the Poisson counting process assumption, we develop an efficient Gibbs sampler based on novel data augmentation for the Markov chain Monte Carlo sampling. Simulation studies show good estimation performance of the baseline mean functions and the regression coefficients; meanwhile, the importance of including the scale parameter to flexibly accommodate the correlation between events is also demonstrated. Finally, a skin cancer data example is fully analyzed to illustrate the proposed methods.

Deubiquitinating enzymes (DUBs) serve to maintain cellular homeostasis via protein ubiquitination and exert diverse regulatory functions in cancers and other diseases. Much progress has been made in characterizing biological roles of DUBs over the decades, yet the specific functions of many subclass members remain largely unexplored. It was not until recent years that the role of ubiquitin‐specific‐processing protease 35 (USP35) in cancers began to be understood. Here, we focus on delineating the roles and underlying mechanisms of USP35 in non‐small cell lung cancer (NSCLC). The isobaric tags for relative and absolute quantitation (iTRAQ) comparative proteomic approach were employed to identify differentially expressed proteins (DEPs) in H1299 cells induced by USP35 overexpression or silencing. Among the potential interactome of USP35, ribosome‐binding protein 1 (RRBP1), a membrane‐bound protein in endoplasmic reticulum (ER), captured our attentions. RRBP1 expression was found to positively correlate with USP35 levels in both genetically modified cells and human NSCLC tissues. Concordantly, both RRBP1 expression and USP35 expression were found to positively correlate with poor prognoses in lung adenocarcinoma patients. At the molecular level, USP35 was verified to directly interact with RRBP1 to prevent it from proteasomal‐dependent degradation. Functionally, USP35 alleviated ER stress‐induced cell apoptosis by stabilizing RRBP1 in NSCLC cells. Collectively, these findings indicate that USP35 plays a critical role in resisting ER stress‐induced cell death through deubiquitinating RRBP1, hence providing a rationale to target the USP35‐RRBP1 axis as an alternative therapeutic option for NSCLC.

BackgroundInfertility has been confirmed as a significant medical and social problem. Heavy metal exposure refers to a risk factor for infertility, which is capable of damaging the reproductive system of males and females. However, heavy metal exposure and female infertility have rarely been investigated. The aim of this study was to analyze the association between heavy metal exposure and female infertility.MethodsA cross-sectional study using data from three cycles of the National Health and Nutrition Examination Survey (NHANES, 2013–2018) was performed. Female infertility was evaluated by positive responses to question rhq074 in the questionnaire. Cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) levels in blood or urine were examined by inductively coupled plasma mass spectrometry. The correlation between heavy metal and female infertility was analyzed through weighted logistic regression.ResultsA total of 838 American women aged 20–44 years were covered in the study. Among all participants, 112 (13.37%) women were subjected to infertility. Urinary Cd and urinary As levels were significantly higher in infertile women than in control women (P < 0.05, P < 0.05). Urinary As showed a positive correlation with the prevalence of female infertility, and the risk of infertility rose with the increase of urinary As levels (P for trend = 0.045). Urinary Cd was associated with female infertility in some weighted logistic regression (Crude, Q2: OR = 3.99, 95% CI 1.82, 8.74, Q3: OR = 2.90, 95% CI 1.42, 5.92. Model 1, Q2: OR = 3.68, 95% CI 1.64, 8.27, Q3: OR = 2.33, 95% CI 1.13, 4.48. Model 2, Q2: OR = 4.11, 95% CI 1.63, 10.07, Q3: OR = 2.44, 95% CI 1.07, 5.53. Model 3, Q2: OR = 3.77, 95% CI 1.52, 9.35). Moreover, blood Pb (OR = 1.52, 95% CI 1.07, 2.16), urinary Pb (OR = 1.68, 95% CI 1.11, 2.55), and urinary As (OR = 1.02, 95% CI 1.00, 1.03) were positively correlated with the risk of infertility in women aged 35–44 years. The blood Pb (OR = 1.67, 95% CI 1.16, 2.40, 2.49) and urinary Pb (OR = 1.54, 95% CI 1.00, 2.38) in women with BMI ≥25 were positively correlated with the risk of infertility.ConclusionsUrinary As was significantly associated with female infertility, and the risk of infertility increased with higher urinary As levels. To some extent, urinary Cd was correlated with infertility. Blood/urine Pb was related to infertility in advanced age and overweight/obese women. The results of this study need to be further validated in future prospective studies.

BackgroundHypoxia-inducible factor 1-alpha (HIF-1α) stability and transcriptional action are reduced by the hypoxia-inducible factor 1-alpha subunit suppressor (HIF1AN). Its inappropriate expression is associated with the development of cancer and immune control. It is yet unknown how HIF1AN, clinical outcomes, and immune involvement in breast cancer (BC) are related.MethodsUsing the GEPIA, UALCAN, TIMER, Kaplan-Meier plotter, and TISIDB datasets, a thorough analysis of HIF1AN differential expression, medical prognosis, and the relationship between HIF1AN and tumor-infiltrating immune cells in BC was conducted. Quantitative real-time PCR (qRT−PCR) analysis of BC cells were used for external validation.ResultsThe findings revealed that, as compared to standard specimens, BC cells had significantly lower levels of HIF1AN expression. Good overall survival (OS) for BC was associated with higher HIF1AN expression. Additionally, in BC, the expression of HIF1AN was closely associated with the chemokines and immune cell infiltration, including neutrophils, macrophages, T helper cells, B cells, Tregs, monocytes, dendritic cells, and NK cells. A high correlation between HIF1AN expression and several immunological indicators of T-cell exhaustion was particularly revealed by the bioinformatic study.ConclusionsHIF1AN is a predictive indicator for breast tumors, and it is useful for predicting survival rates.

ObjectiveTo use the fetal pylorus as a reference point to conveniently display the normal fetal duodenum by ultrasound.MethodsThis study was designed in cross-section. A total of 450 healthy singleton pregnant women at 19–39 weeks of gestation who underwent prenatal screening at our hospital from January 2019 to February 2020 were selected. They were divided into three groups according to gestational weeks: the 19–23 gestational weeks group, 29–32 gestational weeks group, and 34–39 gestational weeks group. The duodenal bulb was identified. Its movement and course were continuously and dynamically observed. The descending part of the duodenum was identified, and the duodenal course was traced.ResultsThe fluid-filled in the fetal duodenum was discontinuous. The overall detection rates of the duodenum in the 19–23 gestational weeks group, 29–32 gestational weeks group, and the 34–39 gestational weeks group were 82.2%, 26.2%, and 13.8%, respectively. The detection rates of the bulbar, descending, horizontal, and ascending parts of the duodenum were 94.4%, 58.2%, 58.0%, and 52.0%, respectively. The anatomical structures of the duodenum as a whole and the pancreas were most easily recognized in the 19–23 gestational weeks group; while in the 34–39 gestational weeks group, the bulbar part had a maximum detection rate of 98.8%, and it had the longest filling time and the shortest examination time.ConclusionThe pylorus is an ideal starting point for tracing the fetal duodenum. The overall detection rate of the fetal duodenum decreases with gestational age. The duodenal bulb is the most easily detected site.

Rapid economic development and industrialization may include environmentally harmful human activities that cause heavy-metal accumulation in soils, ultimately threatening the quality of the soil environment and human health. Therefore, accurate identification of pollution sources is an important weapon in efforts to control and prevent pollution. The self-organizing map (SOM) method is widely used in pollution source identification because of its capacity for visualization of high-dimensional data. The SOM ignores the graph structure relationship among chemical elements in soils; the SOM analysis of pollution sources has high uncertainty. Here, we propose a new analysis method, i.e., the graph convolutional self-organizing map (GCSOM), which uses a graph convolutional network (GCN) to extract the graph structure relationship among the chemical elements in soils, then performs data visualization using an SOM. We compared the performances of GCSOM and SOM, then assessed the pollution source characteristics of trace metal(loid)s (TMs, mostly heavy metals) in Jiangmen City using the GCSOM. Our experimental results showed that the GCSOM is superior to the SOM for identification of TM sources, while the TMs in the soil of Jiangmen originate from three main sources: agricultural activities (mainly in Taishan City, Jiangmen), traffic emissions (mainly in Xinhui and Pengjiang Districts), and industrial activities (mainly in Xinhui District). The risk assessment indicated that the risk of all TMs was within threshold.

The complexity of urban congestion requires policy-makers to adopt different congestion control measures that suit the characteristics of the city at the proper time. The paper focuses on the most controversial congestion pricing and offers methods to judge the efficacy of the policy by game theoretic approaches. It is found that congestion pricing is not merely a Pigouvian tax that internalizes drivers’ externalities, but also a powerful means to enhance public traffic proportion and balance road utilization on the premise of maximized social util-ity. Meanwhile, the embedded multiple case study shows that theoretical correctness of the policy is a necessary, but not sufficient condition for its effectiveness because the valid operation of the policy further requires cities to hold certain attributes in some aspects, such as econom-ic level, population density, proper pricing mechanism, and the ability to limit access to and from certain areas. Moreover, the authority should pay attention to matching the policy goal and its functions for successful implementation.

During post-harvest storage, the cell wall properties are closely associated with the physical, chemical, and biological properties of the fruit. The degradation of pectin in the cell walls and middle lamella is critical to these properties. The effects of calcium chloride (CaCl₂) and 1-methylcyclopropene (1-MCP) combined treatment on the pectin degradation, texture, and peel color of Eureka lemon were investigated during post-harvest storage. The in-situ light microscope analysis, rapid method, and FTIR test were used to investigate the spatial distribution, the pectin content, and its degradation. The results showed a reduction in pectin degradation, by 42 d the CaCl₂ and 1-MCP combined treated fruits presented a 36.7% pectin content loss which was lower than the control which was 48.3%. The treated fruits significantly exhibited enhanced textural properties, delayed weight loss, higher total acids, and improvement of other physicochemical properties in comparison to the control. The treatment deaccelerated the fruit peel color change from green to yellow and also had a better visual appearance on the final day. Overall, the results suggest that the control treatment for pectin degradation can reduce the fruit texture decline and peel color change and maintain a good visual appearance. The influence of pectin degradation on the texture and physicochemical properties of lemon provides a theoretical basis for fruit storage optimization, quality control, and shelf-life extension.

Compared with high-pressure water and reagent washing decontamination, foam decontamination has a promising application due to its ability to significantly reduce the volume of radioactive waste liquids and effectively decontaminate the inner surface of the pipes, the interior of the large cavities, and the vertical walls. However, the foam is less stable, leading to a low decontamination rate. Currently, three main types of stabilizers with different stabilizing mechanisms, namely nanoparticles, polymers, and cosurfactants, are used to improve foam stability and thus increase the decontamination rate. Nanosilica (NS), xanthan gum (XG), and n-tetradecanol (TD) were used as typical representatives of nanoparticles, polymers, and cosurfactants, respectively, to improve the stability of the foam detergent with pH < 2 and chelating agents. The differences in the effects of these three types of stabilizers on foam properties were investigated. Although NS, XG, and TD all increase the half-life of the foam from 7.2 min to about 40 min, the concentration of TD is much lower than that of NS and XG in the foaming solution, and TD foaming solution has the highest foaming ratio. Moreover, TD can markedly lower the surface tension, resulting in a significant reduction of the wetting contact angle on the surfaces of glass, ceramic tile, stainless steel, and paint, while NS and XG cannot signally change the surface tension and have no obvious effect on the wetting contact angle. At low shear rates, TD can increase the apparent viscosity of foam by two orders of magnitude, and the wall-hanging time of the foam on the vertical wall is more than 30 min. In contrast, NS and XG cause a limited increase in the apparent viscosity of the foam, and the wall-hanging times are both less than 5 min. In addition, TD foaming solution has excellent storage stability, and the storage time has no obvious effect on the performance of the foam. And after only three days of storage, NS undergoes severe agglomeration and precipitation in the foaming solution, resulting in a complete loss of the stabilizing effect. After 90 days of storage, the half-life of XG foam decreases by 26%. For simulated radioactive uranium contamination on both horizontal and vertical surfaces, TD can significantly improve the decontamination rate, especially for vertical surfaces, where TD can increase the single decontamination rate by more than 50%.

Summary: Purpose: The goal of this study was to describe the current status of oncology nurses' behaviors toward end of life (EOL) care in China and to explore the factors associated with oncology nurses’ behaviors toward EOL care. Methods: A cross-sectional design was applied and a convenience sample of 1038 oncology nurses from 22 grade A hospitals were recruited into this study. A general social demographic data questionnaire was administered, and the Chinese version of Nurses’ Behaviors of Caring for Dying Patients Scale was used to assess nurse behavior toward EOL care. The total score ranges from 40 to 200 points. Data were analyzed with SPSS 26.0 software. Results: Chinese oncology nurses' average score of holistic EOL care behaviors was 2.97 ± 0.59. Oncology nurses provide physical care most (3.81 ± 0.76), followed by family care (3.02 ± 0.86), and spiritual care (2.37 ± 0.67). Multiple regression analysis showed that a higher frequency of sharing EOL care experience with colleagues, in-service palliative care education, higher level of head nurse support for EOL patient care, more cases of EOL care, higher working position, and nurse's perceived high level of support were positively associated with behavior toward EOL care. These six factors explained 16.2% of the total variance. Conclusions: The results may help provide a basis for converting behavior for EOL care among oncology nurses and design interventions to better improve quality of life for EOL patients with cancer in China.

Abstract In clinical medicine, the pain feeling is a significant indicator for the medical condition of patients. Of late, automatic pain assessment methods have received more and more interests. Many researchers proposed corresponding methods and achieved impressive results. However, they always ignore the locality and individual differences of painful expression. Therefore, a locality and identity aware network (LIAN) for pain assessment is presented here. Concretely, for the locality characteristic, a locality aware module consisting of a two‐branch structure, feature and attention branches, is presented. The former learns pain features by a deep network, while the latter guides the pain features to focus on the discriminational regions of pain. As for the individual differences, an identity aware module with a multi‐task method is proposed to represent identity‐related information to achieve identity‐invariant pain assessment. Extensive experiments on public databases show the superiority of LIAN in pain assessment.

Abstract In advanced atherosclerosis (AS), defective function-induced cell death leads to the formation of the characteristic necrotic core and vulnerable plaque. The forms and mechanisms of cell death in AS have recently been elucidated. Among them, ferroptosis, an iron-dependent form of necrosis that is characterized by oxidative damage to phospholipids, promotes AS by accelerating endothelial dysfunction in lipid peroxidation. Moreover, disordered intracellular iron causes damage to macrophages, vascular smooth muscle cells (VSMCs), vascular endothelial cells (VECs), and affects many risk factors or pathologic processes of AS such as disturbances in lipid peroxidation, oxidative stress, inflammation, and dyslipidemia. However, the mechanisms through which ferroptosis initiates the development and progression of AS have not been established. This review explains the possible correlations between AS and ferroptosis, and provides a reliable theoretical basis for future studies on its mechanism.

Abstract Background Cardiac remodeling is one of the major risk factors for heart failure. In patients with type 2 diabetes, sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of the first hospitalization for heart failure, possibly through glucose-independent mechanisms in part, but the underlying mechanisms remain largely unknown. This study aimed to shed light on the efficacy of dapagliflozin in reducing cardiac remodeling and potential mechanisms. Methods Sprague–Dawley (SD) rats, induced by chronic infusion of Angiotensin II (Ang II) at a dose of 520 ng/kg per minute for 4 weeks with ALZET® mini-osmotic pumps, were treated with either SGLT2 inhibitor dapagliflozin (DAPA) or vehicle alone. Echocardiography was performed to determine cardiac structure and function. Cardiac fibroblasts (CFs) were treated with Ang II (1 μM) with or without the indicated concentration (0.5, 1, 10 μM) of DAPA. The protein levels of collagen and TGF-β1/Smad signaling were measured along with body weight, and blood biochemical indexes. Results DAPA pretreatment resulted in the amelioration of left ventricular dysfunction in Ang II-infused SD rats without affecting blood glucose and blood pressure. Myocardial hypertrophy, fibrosis and increased collagen synthesis caused by Ang II infusion were significantly inhibited by DAPA pretreatment. In vitro, DAPA inhibit the Ang II-induced collagen production of CFs. Immunoblot with heart tissue homogenates from chronic Ang II-infused rats revealed that DAPA inhibited the activation of TGF-β1/Smads signaling. Conclusion DAPA ameliorates Ang II-induced cardiac remodeling by regulating the TGF-β1/Smad signaling in a non-glucose-lowering dependent manner.

Introduction: In a multicenter, open-label, parallel-group, randomized, phase 2 study for pretreated advanced hepatocellular carcinoma (HCC), camrelizumab showed potent antitumor activity and acceptable safety profile. The aim of this report was to provide long-term data and evaluate potential benefit of treatment with camrelizumab beyond progression. Methods: From November 15, 2016, to November 16, 2017, 217 patients received camrelizumab 3 mg/kg intravenously every 2 or 3 weeks. Treatment beyond first Response Evaluation Criteria in Solid Tumors (RECIST)-defined progression (TBP) with camrelizumab was allowed. Results: At data cutoff of December 16, 2019 (>2 years after the last patient enrollment; median duration of follow-up, 13.2 months [IQR 5.7–25.8]), 14 (43.8%) of the 32 responses per blinded independent central review were ongoing. The median duration of response was not reached (range 2.5–30.5 + months). The ongoing response rates at 12, 18, and 24 months were 68.3% (95% confidence interval [CI] 47.7–82.2), 59.8% (95% CI 38.8–75.6), and 53.1% (95% CI 31.0–71.0), respectively. The median overall survival (OS) was 14.2 months (95% CI 11.5–16.3). The 18- and 24-month OS rates were 41.3% (95% CI 34.6–47.9) and 33.7% (95% CI 27.3–40.2), respectively. Of the 172 patients who experienced RECIST-defined progression per investigator, 102 received TBP, while 70 did not (non-TBP). The median OS was 16.9 months (95% CI 13.3–22.6) in the TBP group versus 9.4 months (95% CI 5.8–14.8) in the non-TBP group, and the 18- and 24-month OS rates were 47.5% (95% CI 37.3–56.9) versus 33.1% (95% CI 22.3–44.3) and 38.8% (95% CI 29.2–48.4) versus 23.2% (95% CI 13.8–34.1), respectively. No new safety signals of camrelizumab were observed. Conclusions: With prolonged follow-up, camrelizumab continues to demonstrate the durable response and long survival in pretreated advanced HCC patients with manageable toxicities, especially in those who continued the treatment beyond first RECIST-defined progression.

Isoetes japonica A. Braun is a heterosporous quillwort living in low-altitude areas in Japan. In the present study, the complete chloroplast genome of I. japonica was assembled and annotated. This chloroplast genome is a circular structure of 145,517 bp in length, comprising a pair of inverted repeat (IR) regions of 13,204 bp each, a large single copy (LSC) region of 91,868 bp, and a small single copy (SSC) region of 27,241 bp. The chloroplast genome contains 135 genes, including 78 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. Phylogenetic analysis showed that I. japonica is sister to I. sinensis and I. yunguiensis. These results provide additional resources for the future studies on Isoetes species.

Introduction: Our preclinical work suggests that low-dose angiogenesis inhibition could potentiate programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) blockade. In a cohort of our multicenter phase 1b and 2 study (NCT03083041), promising antitumor activity was observed with camrelizumab plus low-dose apatinib in chemotherapy-pretreated patients with advanced nonsquamous NSCLC. We hereby reported the results in treatment-naive patients (cohort 4) from the same study. Methods: Eligible patients had untreated advanced nonsquamous NSCLC with a high tumor mutational burden (TMB) (tissue TMB >10 mutations per megabase or blood TMB ≥1.54 mutations per megabase) and without sensitizing EGFR or ALK alterations. Patients received camrelizumab 200 mg intravenously every 2 weeks plus apatinib 250 mg orally once daily. The primary end point was the objective response rate (ORR) per investigator. Results: A total of 25 patients were enrolled and treated. A total of 10 (40.0%) confirmed partial responses and 13 (52.0%) stable diseases were observed. The ORR was 40.0% (95% confidence interval [CI]: 21.1–61.3) and disease control rate was 92.0% (95% CI: 74.0–99.0). With a median follow-up of 19.5 months, the median progression-free survival was 9.6 months (95% CI: 5.5–not reached), whereas the overall survival was not reached; the median duration of response was 15.6 months (95% CI: 3.8–not reached). Similar ORR and progression-free survival were observed regardless of PD-L1 tumor proportion score (≥1% versus

MW33 is a fully humanized IgG1κ monoclonal neutralizing antibody, and may be used for the prevention and treatment of coronavirus disease 2019 (COVID-19). We conducted a randomized, double-blind, placebo-controlled, single-dose, dose-escalation Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of MW33. Healthy adults aged 18–45 years were sequentially enrolled into the 4, 10, 20, 40, and 60 mg/kg dose groups and infused with MW33 over 60 ± 15 min and followed for 85 days. All 42 enrolled participants completed the MW33 infusion, and 40 participants completed the 85-day follow-up period. 34 participants received a single infusion of 4 (n = 2), 10 (n = 8), 20 (n = 8), 40 (n = 8), and 60 mg/kg (n = 8) of MW33. 27 subjects in the test groups experienced 78 adverse events (AEs) post-dose, with an incidence of 79.4% (27/34). The most common AEs included abnormal laboratory test results, vascular and lymphatic disorders, and infectious diseases. The severity of AEs was mainly Grade 1 (92 AEs), and three Grade 2 and one Grade 4. The main PK parameters, maximum concentration (Cmax), and area under the concentration-time curve (AUC0–t, and AUC0–∞) in 34 subjects showed a linear kinetic relationship in the range of 10–60 mg/kg. The plasma half-life was approximately 25 days. The positive rates of serum ADAs and antibody titres were low with no evidence of an impact on safety or PK. In conclusion, MW33 was well-tolerated, demonstrated linear PK, with a lower positive rate of serum ADAs and antibody titres in healthy subjects.Trial registration: ClinicalTrials.gov identifier: NCT04427501.Trial registration: ClinicalTrials.gov identifier: NCT04533048.Trial registration: ClinicalTrials.gov identifier: NCT04627584.

Understanding the water use efficiency (WUE) and adaptation strategies of plants in high-temperature and rainy areas is essential under global climate change. The leaf carbon content (LCC) and intrinsic WUE of 424 plant samples (from 312 plant species) on Hainan Island were measured to examine their relationship with geographical and climatic factors in herbs, trees, vines and ferns. The LCC ranged from 306.30 to 559.20 mg g−1, with an average of 418.85 mg g−1, and decreased with increasing mean annual temperature (MAT). The range of intrinsic WUE was 8.61 to 123.39 μmol mol−1 with an average value of 60.66 μmol mol−1. The intrinsic WUE decreased with increasing altitude and relative humidity (RH) and wind speed (WS), but increased with increasing latitude, MAT and rainy season temperature (RST), indicating that geographical and climatic factors affect the intrinsic WUE. Stepwise regression suggested that in tropical regions with high temperature and humidity, the change in plant intrinsic WUE was mainly driven by WS. In addition, the main factors affecting the intrinsic WUE of different plant functional types of plants are unique, implying that plants of different plant functional types have distinctive adaptive strategies to environmental change. The present study may provide an insight in water management in tropical rainforest.

Leaf stoichiometry effectively indicates the response and adaptation of plants to environmental changes. Although numerous studies on leaf stoichiometry patterns have focused on the mid-latitudes and specific species of plants, these patterns and the effect of the climate change on them across a broad range of plants have remained poorly characterized in hot and humid regions at low latitudes. In the present study, leaf N, P, N:P, C:N, and C:P ratios, were determined from 345 plant leaf samples of 268 species at four forest sites in Hainan Island, China. For all plants, leaf N (3.80 ± 0.20 mg g−1) and P (1.82 ± 0.07 mg g−1) were negatively correlated with latitude and mean annual temperature (MAT) but were positively correlated with longitude. Leaf N was found to be positively correlated with altitude (ALT), and leaf P was positively correlated with mean annual precipitation (MAP). The leaf C:N ratio (278.77 ± 15.86) was significantly correlated with longitude and ALT, leaf C:P ratio (390.69 ± 15.15) was significantly correlated with all factors except ALT, and leaf N:P ratio (2.25 ± 0.10) was significantly correlated with ALT, MAT, and MAP. Comparable results were observed for woody plants. The results suggest that leaf stoichiometry on Hainan Island is affected by changes in geographical and climatic factors. In addition, the low N:P ratio indicates that plant growth may be limited by N availability. Moreover, the significant correlation between leaf N and P implies a possible synergistic relationship between N and P uptake efficiency in the plants of this region. This study helps to reveal the spatial patterns of leaf stoichiometry and their response to global climate change in a variety of plants in tropical regions with hot and humid environments, which may provide an insight in nutrient management in tropical rainforest.

The present study aimed to research the effects of cyclic heat environment on the microbial diversity and structure of respiratory tract and cecum of chicken. A total of 360 layer-type pullets at 11 wk of age were subjected to different temperature treatments for 10 wk: constant 22°C; cyclic temperature 22°C to 24°C, 22°C to 26°C, 22°C to 28°C, 22°C to 30°C; the ambient temperature increased from 10:00, reached the set point within 1 h, and maintained until 18:00, thereafter the temperature was restored to 22°C; and the relative humidity was maintained at 60%. The result showed that feed intake of the chickens on ambient temperature 30°C group was significantly lower than that of the chickens on ambient temperature 24°C. The white blood cell, red blood cell, lymphocyte, hemoglobin, and pecked-cell volume content were highest at 24°C on 14, 16, and 18 wk. The ratio of CD3+CD4+/CD3+CD8+ T cells was lowest at 30°C. Meanwhile, the abundance of cecum bacteria in chickens at 30°C was lower than that at 24°C. Cyclic heat environment temperature treatment did not significantly affect the concentration of secretory immunoglobulin A in chicken bronchoalveolar lavage fluid (BALF) levels during 10 wk of trial. The diversity index analysis showed that the effect of 24°C on the cecum flora of chickens was optimal. Abundance of Firmicutes bacteria in the lung flora and cecum flora was lower at 30°C than at 24°C group. Similarly, the microorganism, Brevibacillus in the BALF was also significantly lower at 24°C. In conclusion, cyclic 24°C treatment was beneficial for the feed intake, blood routine indexes, microflora structure of the cecum, and respiratory tract in laying pullets.

The residual levels of 25 monitored pesticides in 6,229 brown rice samples obtained from the 17 provinces of the three main rice-growing regions in China during 2016–2020 were analyzed, and the cumulative risks of chronic and acute exposure to pesticides for the Chinese population were assessed. The QuEChERS extraction coupled with liquid chromatography-mass spectrometry for simultaneous determination of 25 pesticide residues in brown rice was developed and validated with good accuracy and precision (recoveries of 70%–120% and RSD ≤20%). The overall detection rate and over the maximum residue limit (MRL) rate of pesticides in brown rice decreased from 39.15% and 3.59% in 2016 to 34.11% and 1.53% in 2020, respectively. The Yangtze River basin had a higher detection rate and over MRL rate (43.14% and 2.88%, respectively) compared with the Southeast Coastal region (37.28% and 2.77%) and the Northeast Plain (11.28% and 0.17%). Isoprothiolane (13.57%) and carbendazim (8.32%) were the most frequently detected in rice samples. Pesticide residues exceeding the MRLs were found most often in triazophos (0.75%) and isocarbophos (0.51%). The risk ranking of pesticide residues based on the ranking matrix showed that carbofuran, methamidophos, and isocarbophos had the highest residual risk scores of 25.09, 25.01, and 25.00, respectively. 17.7% of rice samples contained two or more pesticide residues. The cumulative risk assessments based on the relative potency factor (RPF) approach revealed that the cumulative risks of chronic and acute dietary exposure to organophosphorus, neonicotinoid insecticides, and triazole fungicides from rice ranged from 7.43 × 10−4 to 3.36 × 10−2, which were not considered of health concern. The study provides national-scale information on the contamination levels and health risks of pesticide residues in rice, which can help develop continuous monitoring programs for pesticide residue contamination in rice in China.

Aims. We aimed to explore whether visceral adiposity indices were significantly associated with obstructive sleep apnea (OSA) in type 2 diabetes (T2DM) patients. Methods. 100 patients with T2DM who underwent overnight polysomnography were analyzed in this study. Anthropometric data, lipid profiles, and glycemic parameters were recorded. Body fat percentage (BFP) and visceral adipose tissue area (VAT area) were collected from a whole body scan using dual-energy X-ray absorptiometry (DXA). Multivariate logistic regression analysis was performed to explore the associations of AHI with BFP, VAT area, and CVAI. Results. The prevalence rate of OSA was 80%, and the mean (±SD) of age was 47.0±13.6 years. Apnea-hypopnea index (AHI) was significantly and positively associated with either VAT area (r=0.433, p≤0.001) or Chinese visceral adiposity index (CVAI) (r=0.355, p≤0.001) but not for BFP (r=0.107, p=0.294). Multivariate logistic regression analyses showed that VAT area and CVAI were significantly associated with increased risk of OSA, and the adjusted ORs were (95% CI) 1.025 (1.003-1.047, p=0.023) and 1.018 (1.002-1.034, p=0.030), respectively. However, there was no significant association between BFP and increased risk of OSA. Conclusions. VAT area and CVAI were independent risk factors of OSA in the patients with T2DM.