Metabolome and microbiome analyses of the anti-fatigue mechanism of Acanthopanax senticosus leaves.

Acanthopanax senticosus leaves, widely used as a vegetable and tea, are reported to be beneficial in treating neurological disorders. At present, their anti-fatigue effect remains to be established. In this study, we analyzed the composition of the extracts from A. senticosus leaves and confirmed their antioxidant and anti-inflammatory properties at the cellular level. In mice subjected to exhaustive running on a treadmill, supplementation with A. senticosus leaf extracts enhanced exercise performance and alleviated fatigue via the reversal of exercise-induced 5-HT elevation, metabolic waste accumulation, organ damage, and glucose metabolism-related gene expression. The collective findings from microbiome and metabolomic analyses indicate that A. senticosus leaf extracts increase α-diversity, regulate microbial composition, and reverse exercise-mediated disruption of carbohydrate, creatine, amino acid, and trimethylamine metabolism. This study provides preliminary evidence for the utility of A. senticosus leaves as a promising anti-fatigue food and offers insights into the underlying mechanism.

Internet addiction and health-related quality of life in adolescents: The mediating role of sleep disturbance.

BACKGROUND: Internet addiction (IA) has emerged as a recognized risk factor associated with impaired health-related quality of life (HRQOL) in adolescents. However, the role of sleep disturbance in this association remains unclear. This study aimed to investigate the association of IA with HRQOL in Chinese adolescents and to evaluate the potential mediating role of sleep disturbance. METHODS: A cross-sectional study was conducted among adolescents attending six randomly selected middle schools in Guangzhou, China. Adolescents self-reported their internet use using the Young Diagnostic Questionnaire. HRQOL and sleep disturbance were assessed by the Pediatric Quality of Life Inventory version 4.0 and the Pittsburgh Sleep Quality Index, respectively. Multivariate linear regression analysis was employed to assess the association between IA and HRQOL. Baron and Kenny's causal steps method was used to examine the possible mediating role of sleep disturbance. RESULTS: Of the 6473 adolescents included, 23.5% had maladaptive internet use (MIU) and 16.6% had pathological internet use (PIU). Compared to adolescents with adaptive internet use (AIU), those with IA had significantly lower scores across all HRQOL dimensions and summary scales. Mediation analysis revealed that sleep disturbance was a significant mediator. Specifically, sleep disturbance mediated 34.55% of the effects of MIU and 34.06% of the effects of PIU on the HRQOL total scale score , respectively. CONCLUSIONS: IA was associated with poorer HRQOL, indicating the needs of preventing IA in Chinese adolescents. Additionally, our findings underscored the importance of enhancing sleep quality to mitigate the adverse impact of IA on adolescents' well-being.

Causal associations between severe mental illness and sepsis: a Mendelian randomization study.

Objective: SMI (severe mental illness) has been identified as a risk factor for sepsis in observational studies; however, the causal association between them has yet to be firmly established. We conducted MR (mendelian randomization) to unveil the causal relationship between SMI and sepsis as well as sepsis mortality. Methods: GWAS (Genome-wide association) data for major depression and schizophrenia were selected as exposure. GWAS data for sepsis and sepsis mortality were selected as outcome. Genetic variants significantly associated with the exposure (P value<1x10-6) were selected as instruments. We primarily employed the IVW (inverse-variance weighted) method for analysis. Furthermore, we employed Cochrane's Q test to assess heterogeneity and the MR-Egger intercept test to identify horizontal pleiotropy. Results: We selected 108 SNPs (single nucleotide polymorphism) used to predict major depression and 260 SNPs that predicted schizophrenia. Genetically predicted major depression was suggestively linked to a higher sepsis risk (OR=1.13, 95%CI 1.02-1.26, P=0.023). In contrast, MR analysis did not find an association between schizophrenia and sepsis risk (OR=1.00, 95%CI 0.97-1.04, P=0.811). Furthermore, no significant causal evidence was found for genetically predicted SMI in sepsis mortality. Moreover, no heterogeneity and horizontal pleiotropy were detected. Conclusion: Our research revealed a suggestive association between genetically predicted major depression and an elevated risk of sepsis in individuals of European ancestry. This finding can serve as a reminder for clinicians to consider the possibility of subsequent infection and sepsis in depressive patients, which may help reduce the incidence of sepsis in individuals with depression.

Lung single-cell RNA profiling reveals response of pulmonary capillary to sepsis-induced acute lung injury.

Background: Sepsis-induced acute lung injury (ALI) poses a significant threat to human health. Endothelial cells, especially pulmonary capillaries, are the primary barriers against sepsis in the lungs. Therefore, investigating endothelial cell function is essential to understand the pathophysiological processes of sepsis-induced ALI. Methods: We downloaded single-cell RNA-seq expression data from GEO with accession number GSE207651. The mice underwent cecal ligation and puncture (CLP) surgery, and lung tissue samples were collected at 0, 24, and 48 h. The cells were annotated using the CellMarker database and FindAllMarkers functions. GO enrichment analyses were performed using the Metascape software. Gene set enrichment Analysis (GSEA) and variation Analysis (GSVA) were performed to identify differential signaling pathways. Differential expression genes were collected with the "FindMarkers" function. The R package AUCell was used to score individual cells for pathway activities. The Cellchat package was used to explore intracellular communication. Results: Granulocytes increased significantly as the duration of endotoxemia increased. However, the number of T cells, NK cells, and B cells declined. Pulmonary capillary cells were grouped into three sub-clusters. Capillary-3 cells were enriched in the sham group, but declined sharply in the CLP.24 group. Capillary-1 cells peaked in the CLP.24 group, while Capillary-2 cells were enriched in the CLP.48 group. Furthermore, we found that Cd74+ Capillary-3 cells mainly participated in immune interactions. Plat+ Capillary-1 and Clec1a+ Capillary-2 are involved in various physiological processes. Regarding cell-cell interactions, Plat+ Capillary-1 plays the most critical role in granulocyte adherence to capillaries during ALI. Cd74+ Capillary cells expressing high levels of major histocompatibility complex (MHC) and mainly interacted with Cd8a+ T cells in the sham group. Conclusion: Plat+ capillaries are involved in the innate immune response through their interaction with neutrophils via ICAM-1 adhesion during endotoxemia, while Cd74+ capillaries epxressed high level of MHC proteins play a role in adaptive immune response through their interaction with T cells. However, it remains unclear whether the function of Cd74+ capillaries leans towards immunity or tolerance, and further studies are needed to confirm this.

Portulaca oleracea L. polysaccharide alleviates dextran sulfate sodium-induced ulcerative colitis by regulating intestinal homeostasis.

Portulaca oleracea L. (purslane) is a vegetable that contains a variety of active compounds with nutritional properties and has the potential to treat ulcerative colitis (UC). However, the mechanisms underlying the effects of Portulaca oleracea L. polysaccharide (POP) in alleviating UC remain unclear. In this study, we prepared an aqueous extract of purslane and separated a fraction with molecular weight >10 kDa using membrane separation. This fraction was used to isolate POP. The effect of POP on gut microbiota and colon transcriptome in dextran sulfate sodium-induced UC model mice was evaluated. POP treatment reduced inflammation and oxidative stress imbalance in UC mice. In addition, POP improved the intestinal barrier and regulated intestinal homeostasis. Importantly, POP was found to regulate gut microbiota, maintain the levels of retinol and short-chain fatty acids in the gut, promote the proliferation and differentiation of B cells in the colon, and increase the expression of immunoglobulin A. These results provide novel insights into the role of POP in regulating intestinal homeostasis, which should guide further development of POP as a functional food.

A Keggin Al13 -Montmorillonite Modified Separator Retards the Polysulfide Shuttling and Accelerates Li-Ion Transfer in Li-S Batteries.

The commercialization of Li-S batteries as a promising energy system is terribly impeded by the issues of the shuttle effect and Li dendrite. Keggin Al13 -pillared montmorillonite (AlMMT), used as the modified film of the separator together with super-P and poly (vinylidene fluoride) (PVDF), has a good chemical affinity to lithium polysulfide (LiPS) to retard the polysulfide shuttling, excellent electrolyte wettability, and a stable structure, which can improve the rate capability and cycling stability of Li-S batteries. Density function theory (DFT) calculations reveal the strong adsorption ability of AlMMT for LiPS. Consequently, the modified film allows Li-S batteries to reach 902 mAh g-1 at 0.2C after 200 cycles and 625 mAh g-1 at 1C after 1000 cycles. More importantly, a high reversible areal capacity of 4.04 mAh cm-2 can be realized under a high sulfur loading of 6.10 mg cm-2 . Combining the merits of rich resources of montmorillonite, prominent performance, simple operation and cost-effectiveness together, this work exploits a new route for viable Li-S batteries for applications.

Association between healthy lifestyle factors and health-related quality of life among Chinese adolescents: the moderating role of gender.

BACKGROUND: To examine the associations of the independent and combined healthy lifestyle factors with health-related quality of life (HRQOL) in adolescents, and to test the moderating role of gender. METHODS: This cross-sectional study included 5125 adolescents aged between 11 and 20 years. They provided self-reported data on six healthy lifestyle factors, including never smoking, never drinking, good sleep quality, sufficient sleep duration, appropriate Internet use, and adequate physical activity. Adolescents' HRQOL was evaluated using the Pediatric Quality of Life Inventory version 4.0. Linear regression models were conducted to explore the association of individual and combined healthy lifestyle factors with adolescents' HRQOL. We further performed stratified analyses and likelihood ratio test to explore the moderating role of gender in these associations. RESULTS: Of the included adolescents, the proportions with 0-2, 3, 4, and 5-6 healthy lifestyle factors were 13.6%, 26.4%, 44.3%, and 15.7%, respectively. Compared to adolescents with composite healthy lifestyle scores of 0-2, those with scores of 3, 4, or 5-6 had significantly higher HRQOL scores across all dimensions, summary scales, and total scale in both unadjusted and adjusted models. Specifically, adolescents with 5-6 healthy lifestyle factors had a total scale score that was 19.03 (95%CI: 17.76 to 20.30) points higher than their counterparts who only had 0-2 healthy lifestyle factors. Significant dose-response patterns were also observed in aforementioned associations. Gender was a significant moderator in the associations between composite healthy lifestyle groups and HRQOL scores, except for the social functioning dimension. CONCLUSIONS: Our results confirmed that combined healthy lifestyle factors were associated with improved HRQOL among adolescents, with a stronger association observed in girls. These findings underscore the necessity for education and healthcare authorities to design health-promoting strategies that encourage multiple healthy lifestyle factors in adolescents, with the objective of enhancing their overall health outcomes.

A multicenter study of the clinicopathological characteristics and a risk prediction model of early-stage breast cancer with hormone receptor-positive/human epidermal growth factor receptor 2-low expression.

BACKGROUND: In light of the significant clinical benefits of antibody-drug conjugates in clinical trials, the human epidermal growth factor receptor 2 (HER2)-low category in breast cancers has gained increasing attention. Therefore, we studied the clinicopathological characteristics of Chinese patients with hormone receptor (HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model. METHODS: Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery (CSBrS) from Jan 2015 to Dec 2016 were enrolled. Their clinicopathological data and prognostic information were collected, and machine learning methods were used to analyze the prognostic factors. RESULTS: In total, 25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016, and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected. Among them, 5629 patients (86.79%) were HR-positive. The median follow-up time was 57 months (4, 76 months); the 5-year disease-free survival (DFS) rate was 92.7%, and the 5-year overall survival (OS) rate was 97.7%. In total, 412 cases (7.31%) of metastasis were observed, and 124 (2.20%) patients died. Multivariate Cox regression analysis revealed that T stage, N stage, lymphovascular thrombosis, Ki-67 index, and prognostic stage were associated with recurrence and metastasis ( P <0.05). A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%, specificity of 71.7%, positive predictive value of 74.1%, and negative predictive value of 79.2%. CONCLUSION: Most of patients with HER2-low early-stage breast cancer were HR-positive, and patients had favorable outcome; tumor N stage, lymphovascular thrombosis, Ki-67 index, and tumor prognostic stage were prognostic factors. The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events. REGISTRITATION: ChiCTR.org.cn, ChiCTR2100046766.

Integrated network analysis and metabolomics reveal the molecular mechanism of Yinchen Sini decoction in CCl4-induced acute liver injury.

Objective: Yinchen Sini decoction (YCSND), a traditional Chinese medicine (TCM) formula, plays a crucial role in the treatment of liver disease. However, the bioactive constituents and pharmacological mechanisms of action remain unclear. The present study aimed to reveal the molecular mechanism of YCSND in the treatment of acute liver injury (ALI) using integrated network analysis and metabolomics. Methods: Ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) was utilized to identify metabolites in YCSND, and high-performance liquid chromatography (HPLC) was applied to evaluate the quality of four botanical drugs in YCSND. Cell damage and ALI models in mice were established using CCl4. 1H-NMR metabolomics approach, along with histopathological observation using hematoxylin and eosin (H&E), biochemical measurements, and reverse transcription quantitative real-time PCR (RT-qPCR), was applied to evaluate the effect of YCSND on CCl4- induced ALI. Network analysis was conducted to predict the potential targets of YCSND in ALI. Result: Our results showed that 89 metabolites in YCSND were identified using UHPLC-QE-MS. YCSND protected against ALI by reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) contents and increasing those of superoxide dismutase (SOD), and glutathione (GSH) both in vivo and in vitro. The 1H-NMRmetabolic pattern revealed that YCSND reversed CCl4-induced metabolic abnormalities in the liver. Additionally, the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis identified five pathways related to liver injury, including the PI3K-AKT, MAPK, HIF-1, apoptosis, and TNF signaling pathways. Moreover, RT-qPCR showed YCSND regulated the inflammatory response (Tlr4, Il6, Tnfα, Nfκb1, Ptgs2, and Mmp9) and apoptosis (Bcl2, Caspase3, Bax, and Mapk3), and inhibited PI3K-AKT signaling pathway (Pi3k and Akt1). Combined network analysis and metabolomics showed a link between the key targets (Tlr4, Ptgs2, and Mmp9) and vital metabolites (choline, xanthine, lactate, and 3-hydroxybutyric acid) of YCSND in ALI. Conclusion: Overall, the results contribute to the understanding of the therapeutic effects of YCSND on ALI, and indicate that the integrated network analysis and metabolomics could be a powerful strategy to reveal the pharmacological effects of TCM.

Comparison of adverse effects of anti-tumor therapy for breast cancer shortly after COVID-19 diagnosis vs. the control period.

Background: COVID-19 is an acute infectious disease caused by SARS-CoV-2. The best time to restart antitumor therapy in breast cancer patients after SARS-CoV-2 infection is unknown. This study aimed to evaluate treatment-related adverse events in breast cancer patients who received antitumor therapies within a short time after SARS-CoV-2 infection (observation) as well as before (control) and to provide safety data. Methods: We conducted a self-controlled cohort study using the data from the Breast Disease Center of Peking University First Hospital. We identified patients who received antitumor therapy within 28 days after COVID-19 infection between December 20, 2022, and January 20, 2023. The primary outcome was treatment-related adverse events. McNemar's test was used to compare the incidence rate of adverse reactions between periods. Results: We identified 183 patients with breast cancer, of whom 109 were infected with SARS-CoV-2 within 28 days before antitumor treatment and were included. In total, 28 patients (25.7%) received neoadjuvant therapy, 60 (55.0%) received adjuvant therapy, and 21 (19.3%) received advanced rescue therapy. None of patients required hospitalization for severe or critical COVID-19, but 15 patients (13.8%) still had sequelae of COVID-19 while receiving antitumor treatment. The most common adverse events were peripheral neuropathy (n = 32 [29.4%]), pain (n = 29 [26.6%]), fatigue (n = 28 [25.7%]), nausea (n = 23 [21.1%]), and neutropenia (n = 19 [17.4%]). There was no increased risk of overall treatment-related adverse events (n = 87 [79.8%] vs. n = 91 [83.5%]; p = 0.42) or serious adverse events (n = 13 [11.9%] vs. n = 12 [11.0%]; p = 1.00) from receiving antitumor therapy shortly after the diagnosis of COVID-19. We also found no increased risk in subgroup analyses, and no patients discontinued antitumor therapy due to adverse events. Conclusion: Restarting antitumor therapy 2-4 weeks after having mild or moderate COVID-19 is a relatively safe strategy for breast cancer patients that does not increase the risk of treatment-related adverse events.

iTRAQ-based proteomic analysis of imiquimod in the treatment of ulcerative colitis.

OBJECTIVE: In this study, we explored the potential mechanisms and the signaling pathways involved in the treatment of Ulcerative Colitis (UC) with imiquimod (IMQ). METHODS: The UC mouse model was established by treating C57BL/6J mice with 3% Dextran Sulfate Sodium (DSS). Then, the UC-related symptoms were examined. Disease Activity Index (DAI) was estimated based on weight loss, stool consistency, and occult bleeding or hematochezia. Histological changes were evaluated by Hematoxylin and Eosin (H&E) staining. Furthermore, we used multiplexed Isobaric Tagging for Relative and Absolute Protein Quantification (iTRAQ) technique coupled with high-throughput liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the differentially expressed proteins (DEPs). RESULTS: Administration of 3% DSS for 7 days induced acute colitis associated with diarrhea, hematochezia, weight loss, and colon shortening. However, after IMQ administration, almost all the above symptoms were improved by different degrees. Specifically, the DAI, histological disorder, and colon shortening were attenuated. In iTRAQ analysis, a total of 4170 proteins were identified with a high confidence (≥ 95% confidence). The numbers of DEPs between the normal and UC model mice, between the normal and the IMQ-treated therapy mice, as well as between the model and the therapy mice were 317, 253, and 209, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the DEPs involved in the complement and coagulation cascades were downregulated in IMQ-treated therapy group. CONCLUSIONS: IMQ might ameliorate colitis by suppressing the complement and coagulation cascades pathway, which might serve as new therapeutic strategies for the treatment of patients with UC.

Protective Effects of Different Molecular Weights of Purslane (Portulaca oleracea L.) Aqueous Extract on DSS-Induced Ulcerative Colitis in Mice.

Purslane, a common wild vegetable, contains active substances with various biological functions. However, its effects have been under-investigated in ulcerative colitis (UC). Therefore, this study investigated the therapeutic effects of purslane macromolecular (POEM) and small molecular extracts (POES) on dextran sulfate sodium (DSS)-induced UC in mice. Membrane separation was used to obtain extracts of different molecular weights, and their compositional differences were compared using liquid chromatography-mass spectrometry (LC/MS). POEM contained more proteins and polysaccharides, whereas POES contained more organic acids and alkaloids. These differences in composition were directly responsible for the different degrees of remission of the alleviated UC in model mice. POEM may alleviate UC by regulating the antioxidant capacity and the gut microbiota, whereas the major alleviatory effect of POES was primarily related to the regulation of antioxidant capacity. The POEM and POES effects identified in this study provide a theoretical basis for the development of purslane as a functional food.

Lysimachia christinae polysaccharide attenuates diet-induced hyperlipidemia via modulating gut microbes-mediated FXR-FGF15 signaling pathway.

Polysaccharides are one of the most abundant and active components of Lysimachia christinae (L. christinae), which is widely adopted for attenuating abnormal cholesterol metabolism; however, its mechanism of action remains unclear. Therefore, we fed a natural polysaccharide (NP) purified from L. christinae to high-fat diet mice. These mice showed an altered gut microbiota and bile acid pool, which was characterized by significantly increased Lactobacillus murinus and unconjugated bile acids in the ileum. Oral administration of the NP reduced cholesterol and triglyceride levels and enhanced bile acid synthesis via cholesterol 7α-hydroxylase. Additionally, the effects of NP are microbiota-dependent, which was reconfirmed by fecal microbiota transplantation (FMT). Altered gut microbiota reshaped bile acid metabolism by modulating bile salt hydrolase (BSH) activity. Therefore, bsh genes were genetically engineered into Brevibacillus choshinensis, which was gavaged into mice to verify BSH function in vivo. Finally, adeno-associated-virus-2-mediated overexpression or inhibition of fibroblast growth factor 15 (FGF15) was used to explore the farnesoid X receptor-fibroblast growth factor 15 pathway in hyperlipidemic mice. We identified that the NP relieves hyperlipidemia by altering the gut microbiota, which is accompanied by the active conversion of cholesterol to bile acids.

Adverse childhood experiences, problematic internet use, and health-related quality of life in Chinese adolescents.

Background: The influence of adverse childhood experiences (ACEs) on an individual's health is substantial. However, the associations between ACEs, problematic internet use (PIU), and health-related quality of life (HRQOL) in adolescents remain underexplored.Objective: To assess the association between ACEs and HRQOL in Chinese adolescents and to evaluate the mediating role of PIU in this association.Method: A sample of 6,639 adolescents (3,457 boys and 3,182 girls) aged between 11-20 years (mean [SD] age: 14.5 [1.6] years) were recruited from 6 junior and senior middle schools using a proportional sampling approach in a cross-sectional study. Data on ACE exposure was collected through the short form of Childhood Trauma Questionnaire, the ACE-International Questionnaire, and two additional questions. HRQOL was assessed by the Pediatric Quality of Life Inventory version 4.0. The associations between ACEs and HRQOL were estimated using linear regression models. Mediation analysis was further conducted to explore the possible mediating role of PIU in the association between ACEs and HRQOL.Results: Our study collected 13 different ACEs. We found that adolescents exposed to any ACE had significantly lower scores in all HRQOL dimensions, psychosocial health summary scale, and total scale, than those without such exposure. Specifically, adolescents with ≥ 3 ACE exposure had a total scale score that was 14.70 (95%CI: 15.53 to 13.87) points lower than their non-exposed counterparts. Mediation analysis identified PIU as a significant mediator, with the proportion of the total effect attributable to PIU ranging from 14.38% for social functioning to 17.44% for physical functioning.Conclusions: Exposure to ACEs was associated with poorer HRQOL in Chinese adolescents, underscoring the importance to prevent ACEs and their negative impacts on adolescent well-being. These findings also highlighted the need of promoting appropriate internet use among adolescents exposed to ACEs, in order to avert potential impairment in their HRQOL.HIGHLIGHTSAdolescents with adverse childhood experiences have poorer health-related quality of life.The association between adverse childhood experiences and health-related quality of life shows a dose-response pattern.Problematic internet use partially mediates the associations between adverse childhood experiences and health-related quality of life in adolescents.

Study on optimization of multi-UAV nucleic acid sample delivery paths in large cities under the influence of epidemic environment.

In the context of global novel coronavirus infection, we studied the distribution problem of nucleic acid samples, which are medical supplies with high urgency. A multi-UAV delivery model of nucleic acid samples with time windows and a UAV (Unmanned Aerial Vehicle) dynamics model for multiple distribution centers is established by considering UAVs' impact cost and trajectory cost. The Golden Eagle optimization algorithm (SGDCV-GEO) based on gradient optimization and Corsi variation is proposed to solve the model by introducing gradient optimization and Corsi variation strategy in the Golden Eagle optimization algorithm. Performance evaluation by optimizing test functions, Friedman and Nemenyi test compared with Golden Jackal Optimization (GJO), Hunter-Prey Optimization (HPO), Pelican Optimization Algorithm (POA), Reptile Search Algorithm (RSA) and Golden Eagle Optimization (GEO), the convergence performance of SGDCV-GEO algorithm was demonstrated. Further, the improved RRT (Rapidly-exploring Random Trees) algorithm is used in the UAV path planning, and the pruning process and logistic chaotic mapping strategy are introduced in the path generation method. Finally, simulation experiments are conducted based on 8 hospitals and 50 randomly selected communities in the Pudong district of Shanghai, southern China. The experimental results show that the developed algorithm can effectively reduce the delivery cost and total delivery time compared with simulated annealing algorithm (SA), crow search algorithm (CSA), particle swarm algorithm (PSO), and taboo search algorithm (TS), and the developed algorithm has good uniformity, robustness, and high convergence accuracy, which can be effectively applied to the multi-UAV nucleic acid sample delivery path optimization in large cities under the influence of an epidemic environment.

Interferon-γ secreted by recruited Th1 cells in peritoneal cavity inhibits the formation of malignant ascites.

Type 1 T helper (Th1) cells generate an efficient antitumor immune response in multiple malignancies. The functions of Th1 cells in malignant ascites (MA) have not been elucidated. The distribution of helper T cells in peritoneal fluid and peripheral blood was determined in patients and animal models with malignant ascites. The effects of Th1-derived interferon-γ (IFN-γ) on the formation of malignant ascites were investigated. The mechanism underlying the recruitment of Th1 cells into peritoneal cavity was explored. In patients with malignant ascites and animal models of malignant ascites, the percentage of Th1 cells increased in peritoneal fluid compared with peripheral blood. Next, our experiment demonstrated that Th1 cells inhibited the growth of tumor cells by secreting IFN-γ in vitro. In murine models of malignant ascites, increased peritoneal fluid and shorter survival time were observed in IFN-γ-/- mice compared with wild-type (WT) mice. Then, the levels of C-X-C motif chemokine ligand (CXCL) 9/10 and the ratio of CXCR3+ Th1 cells indicated the involvement of CXCL9, 10/CXCR3 axis in the recruitment of Th1 cells into peritoneal cavity. As expected, in murine models of malignant ascites, the gradient between ascitic Th1 ratio and blood Th1 ratio decreased in CXCR3-/- mice compared with WT mice. IFN-γ secreted by recruited Th1 cells in peritoneal cavity inhibits the formation of malignant ascites. Hence, manipulation of Th1 cells or IFN-γ will provide a therapeutic candidate against malignant ascites.

Enoxaparin attenuates pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome by inhibiting oncostatin M expression.

BACKGROUND AND AIMS: The definitive treatment for pyrrolizidine alkaloids (PAs)-induced hepatic sinusoidal obstruction syndrome (HSOS) is not available. The effectiveness of anticoagulation therapy remains controversial. The efficacy of low molecular weight heparin (LMWH) should be investigated in patients and animal models, and the underlying mechanism should be explored. METHODS: The prognosis of patients with PAs-HSOS who received anticoagulation therapy was retrospectively analysed. The effect of enoxaparin on the liver injury was determined in animal models of monocrotaline (MCT)-induced HSOS was determined, and the underlying mechanism was investigated using a murine model. RESULTS: The cumulative survival rate of patients with PAs-induced HSOS was 60.00% and 90.90% in the non-anticoagulation group and anticoagulation group. Enoxaparin attenuated liver injury effectively in a rat model of MCT-induced HSOS. Additionally, the improvement of severe liver injury was observed in MCT-treated mice after the administration of enoxaparin (40 mg/kg). The alleviation of liver injury was observed in mice with hepatocyte-specific deletion of oncostatin M (Osm△Hep ). In MCT-treated mice administrated with enoxaparin, no significant differences in liver injury were observed between Osm△Hep mice and Osmflox/flox mice. Additionally, adenovirus-mediated overexpression of Osm resulted in severe liver injury in MCT-induced mice after the administration of enoxaparin. CONCLUSIONS: LMWH attenuated severe liver injury in patients with PAs-Induced HSOS and animal models of MCT-induced HSOS, which provides a rationale for the application of anticoagulation therapy.

A multicenter study on efficacy of dual-target neoadjuvant therapy for HER2-positive breast cancer and a consistent analysis of efficacy evaluation of neoadjuvant therapy by Miller-Payne and RCB pathological evaluation systems (CSBrS-026).

Objective: The aim of this study was to investigate the factors influencing pathological complete response (pCR) rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab (H) + pertuzumab (P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden (RCB) systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2 (HER2)+ breast cancer was analyzed. Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery (CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry (IHC) 3+/hormone receptor (HR)-, IHC3+/HR+, IHC2+ in situ hybridization (ISH)+/HR- and IHC2+ ISH+/HR+ groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed. Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals; 18,853 (24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target (H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate (P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0% (κ=0.717, P<0.001). Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+ breast cancer.

Correlation between Androgen Receptor Expression in Luminal B (HER-2 Negative) Breast Cancer and Disease Outcomes.

(1) Background: Hormone receptor positive breast cancer is a subtype of breast cancer with relatively good prognosis, but luminal B (HER−2 negative) breast cancer has a higher risk of recurrence and metastasis. Patients with endocrine therapy resistance and chemotherapy insensitivity have poor prognosis. Androgen receptor (AR) is widely expressed in breast cancer, but there is no clear conclusion about its function and correlation with prognosis in luminal B breast cancer. Further research is needed to reveal the role of AR in luminal B (HER−2 negative) breast cancer. (2) Methods: Retrospectively analyzed patients with early−stage luminal B breast cancer. The correlation between AR and its associated indexes with long−term survival was determined. (3) Results: A total of 985 patients were included with 143 treated by neoadjuvant therapy. Of these, 83.5% of the patients had AR expression ≥65%. High AR expression was associated with good disease−free survival (DFS) and overall survival (OS). In the neoadjuvant population, AR/estrogen receptor (ER) > 1.06 and residual tumor Ki67 > 23% had significantly worse DFS. (4) Conclusion: Low AR (<65%) expression is associated with poor prognosis in luminal B (HER−2 negative) breast cancer patients. High AR/ER and residual tumor Ki67 were associated with poor DFS in neoadjuvant group with a cutoff value of AR/ER > 1.06 and residual tumor Ki67 > 23%.

Neoadjuvant therapy for early human epidermal growth factor receptor 2 positive breast cancer in China: A multicenter real-world study (CSBrS-015).

BACKGROUND: Pertuzumab has been approved for application in China by the National Medical Products Administration, and both national and international guidelines make recommendations for the use of neoadjuvant treatment with trastuzumab or trastuzumab + pertuzumab plus chemotherapy regimens for patients with indications. The goal of this study was to investigate the short-term clinical efficacy of the neoadjuvant therapies trastuzumab and trastuzumab+pertuzumab for patients with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer in China. METHODS: A real-world study was conducted using the clinicopathological data of patients with early HER2-positive breast cancer who were admitted to the member hospitals of the Chinese Society of Breast Surgery, Chinese Surgical Society of Chinese Medical Association between March 2019 and December 2020. This study analyzed the efficacy and tolerance of trastuzumab+chemotherapy and trastuzumab+pertuzumab+chemotherapy in patients with early HER2-positive breast cancer. The Response Evaluation Criteria in Solid Tumors 1.1 was adopted to evaluate clinical efficacy. The pathological efficacy was evaluated using the MillerPayne grade. The Common Terminology Criteria for Adverse Events (version 5.0) was adopted to evaluate adverse events (AEs). The propensity scores were subjected to propensity score matching using the R language (1:1 matching with a maximum allowable difference of 0.05 between the two groups). Efficacy was compared using the chi-square test, and correlation analysis was performed using linear regression. RESULTS: A total of 1032 patients with early HER2-positive breast cancer met the enrollment criteria and were included in this study. Among these patients, 472 received neoadjuvant trastuzumab+chemotherapy (the trastuzumab group), and 560 received neoadjuvant trastuzumab+pertuzumab+chemotherapy (the trastuzumab+pertuzumab group). The overall pathologic complete response (pCR) rate was 47.2% (487/1032), while the pCR rates of the trastuzumab and trastuzumab+pertuzumab groups were 34.5% (163/472) and 57.9% (324/560), respectively, and the difference was significant (P < 0.001). The incidence of grade 4 AEs was 24/321 (7.5%) in the trastuzumab+pertuzumab group, and there were no cases in which the left ventricular ejection fraction decreased by more than 10%. CONCLUSIONS: Patients in the trastuzumab+pertuzumab group had a higher pCR rate than those in the trastuzumab group, and the toxic side effects were tolerable.