Protocol for deep mining the correlation between acute pancreatitis and ferroptosis using the MIMIC-III database and STATA software.

The limitations associated with distinguishing serum Fe2+ and Fe3+ hinder the widespread application of ferroptosis, beyond laboratory settings. Here, we present a protocol for deep mining the correlation between acute pancreatitis and ferroptosis using the MIMIC-III database and STATA software. We describe steps for using Cox regression, decision curve analysis (DCA), and receiver operating characteristic (ROC) approaches to establish the relationship between them and determine the relevant factors. This protocol has potential application in establishing novel research models that integrate both fundamental and clinical methodologies. For complete details on the use and execution of this protocol, please refer to Yueling Deng et al.1.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

Wand-Based Calibration of Unsynchronized Multiple Cameras for 3D Localization.

Three-dimensional (3D) localization plays an important role in visual sensor networks. However, the frame rate and flexibility of the existing vision-based localization systems are limited by using synchronized multiple cameras. For such a purpose, this paper focuses on developing an indoor 3D localization system based on unsynchronized multiple cameras. First of all, we propose a calibration method for unsynchronized perspective/fish-eye cameras based on timestamp matching and pixel fitting by using a wand under general motions. With the multi-camera calibration result, we then designed a localization method for the unsynchronized multi-camera system based on the extended Kalman filter (EKF). Finally, extensive experiments were conducted to demonstrate the effectiveness of the established 3D localization system. The obtained results provided valuable insights into the camera calibration and 3D localization of unsynchronized multiple cameras in visual sensor networks.

Multivariate Analysis Compares and Evaluates Heat Tolerance of Potato Germplasm.

High temperature is the most important environmental factor limiting potato (Solanum tuberosum L.) yield. The tuber yield has been used to evaluate the heat tolerance of some potato cultivars, but potato yield was closely correlated with the maturation period. Therefore, it is necessary to employ different parameters to comprehensively analyze and evaluate potato tolerance to heat stress. This study aimed to investigate physiologic changes during growth and development, and develop accurate heat tolerance evaluation methods of potato cultivars under heat stress. About 93 cultivars (including foreign elite lines, local landraces and cultivars) were screened using an in vitro tuber-inducing system (continuous darkness and 8% sucrose in the culture medium) under heat stress (30 °C) and normal (22 °C) conditions for 30 days. The tuber yield and number decreased significantly under heat stress compared to the control. A total of 42 cultivars were initially selected depending on tuber formation, after in vitro screening, further testing of selected cultivars was conducted in ex vitro conditions. The screened cultivars were further exposed to heat stress (35 °C/28 °C, day/night) for 60 days. Heat stress led to an increase in the plant height growth rate, fourth internode growth rate, and membrane damage, and due to heat-induced damage to chloroplasts, decrease in chlorophyll biosynthesis and photosynthetic efficiency. Three principal components were extracted by principal component analysis. Correlation and regression analysis showed that heat tolerance is positively correlated with the plant height growth rate, fourth internode growth rate, the content of chlorophyll b, photosynthetic rate, stomatal conductance, transpiration rate, tuber number, and tuber yield, and negatively correlated with the cell membrane injury level. The nine traits are accurate and representative indicators for evaluating potato tolerance to heat stress and could determine a relatively high mean forecast accuracy of 100.0% for the comprehensive evaluation value. Through cluster analysis and screening, cultivar FA, D73, and C132 had the highest heat comprehensive evaluation value, which could be further selected as heat-resistant varieties. This study provides insights into the different physiological mechanisms and accurate evaluation methods of potato cultivars under heat stress, which could be valuable for further research and breeding.

A Novel Vectorized Curved Road Representation Based Aerial Guided Unmanned Vehicle Trajectory Planning.

Unmanned vehicles frequently encounter the challenge of navigating through complex mountainous terrains, which are characterized by numerous unknown continuous curves. Drones, with their wide field of view and ability to vertically displace, offer a potential solution to compensate for the limited field of view of ground vehicles. However, the conventional approach of path extraction solely provides pixel-level positional information. Consequently, when drones guide ground unmanned vehicles using visual cues, the road fitting accuracy is compromised, resulting in reduced speed. Addressing these limitations with existing methods has proven to be a formidable task. In this study, we propose an innovative approach for guiding the visual movement of unmanned ground vehicles using an air-ground collaborative vectorized curved road representation and trajectory planning method. Our method offers several advantages over traditional road fitting techniques. Firstly, it incorporates a road star points ordering method based on the K-Means clustering algorithm, which simplifies the complex process of road fitting. Additionally, we introduce a road vectorization model based on the piecewise GA-Bézier algorithm, enabling the identification of the optimal frame from the initial frame to the current frame in the video stream. This significantly improves the road fitting effect (EV) and reduces the model running time (T-model). Furthermore, we employ smooth trajectory planning along the "route-plane" to maximize speed at turning points, thereby minimizing travel time (T-travel). To validate the efficiency and accuracy of our proposed method, we conducted extensive simulation experiments and performed actual comparison experiments. The results demonstrate the superior performance of our approach in terms of both efficiency and accuracy.

Multi-omics integrated circulating cell-free DNA genomic signatures enhanced the diagnostic performance of early-stage lung cancer and postoperative minimal residual disease.

BACKGROUND: Liquid biopsy is a promising non-invasive alternative for cancer screening and minimal residual disease (MRD) detection, although there are some concerns regarding its clinical applications. We aimed to develop an accurate detection platform based on liquid biopsy for both cancer screening and MRD detection in patients with lung cancer (LC), which is also applicable to clinical use. METHODS: We applied a modified whole-genome sequencing (WGS) -based High-performance Infrastructure For MultIomics (HIFI) method for LC screening and postoperative MRD detection by combining the hyper-co-methylated read approach and the circulating single-molecule amplification and resequencing technology (cSMART2.0). FINDINGS: For early screening of LC, the LC score model was constructed using the support vector machine, which showed sensitivity (51.8%) at high specificity (96.3%) and achieved an AUC of 0.912 in the validation set prospectively enrolled from multiple centers. The screening model achieved detection efficiency with an AUC of 0.906 in patients with lung adenocarcinoma and outperformed other clinical models in solid nodule cohort. When applied the HIFI model to real social population, a negative predictive value (NPV) of 99.92% was achieved in Chinese population. Additionally, the MRD detection rate improved significantly by combining results from WGS and cSMART2.0, with sensitivity of 73.7% at specificity of 97.3%. INTERPRETATION: In conclusion, the HIFI method is promising for diagnosis and postoperative monitoring of LC. FUNDING: This study was supported by CAMS Innovation Fund for Medical Sciences, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, Beijing Natural Science Foundation and Peking University People's Hospital.

CRISPR/FnCas12a-mediated efficient multiplex and iterative genome editing in bacterial plant pathogens without donor DNA templates.

CRISPR-based genome editing technology is revolutionizing prokaryotic research, but it has been rarely studied in bacterial plant pathogens. Here, we have developed a targeted genome editing method with no requirement of donor templates for convenient and efficient gene knockout in Xanthomonas oryzae pv. oryzae (Xoo), one of the most important bacterial pathogens on rice, by employing the heterologous CRISPR/Cas12a from Francisella novicida and NHEJ proteins from Mycobacterium tuberculosis. FnCas12a nuclease generated both small and large DNA deletions at the target sites as well as it enabled multiplex genome editing, gene cluster deletion, and plasmid curing in the Xoo PXO99A strain. Accordingly, a non-TAL effector-free polymutant strain PXO99AD25E, which lacks all 25 xop genes involved in Xoo pathogenesis, has been engineered through iterative genome editing. Whole-genome sequencing analysis indicated that FnCas12a did not have a noticeable off-target effect. In addition, we revealed that these strategies are also suitable for targeted genome editing in another bacterial plant pathogen Pseudomonas syringae pv. tomato (Pst). We believe that our bacterial genome editing method will greatly expand the CRISPR study on microorganisms and advance our understanding of the physiology and pathogenesis of Xoo.

In vitro co-culture systems of hepatic and intestinal cells for cellular pharmacokinetic and pharmacodynamic studies of capecitabine against colorectal cancer.

BACKGROUND: As a prodrug of 5-fluorouracil (5-FU), orally administrated capecitabine (CAP) undergoes preliminary conversion into active metabolites in the liver and then releases 5-FU in the gut to exert the anti-tumor activity. Since metabolic changes of CAP play a key role in its activation, a single kind of intestinal or hepatic cell can never be used in vitro to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) nature. Hence, we aimed to establish a novel in vitro system to effectively assess the PK and PD of these kinds of prodrugs. METHODS: Co-culture cellular models were established by simultaneously using colorectal cancer (CRC) and hepatocarcinoma cell lines in one system. Cell Counting Kit-8 (CCK-8) and flow cytometric analysis were used to evaluate cell viability and apoptosis, respectively. Apoptosis-related protein expression levels were measured using western blot analysis. A selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for cellular PK in co-culture models. RESULTS: CAP had little anti-proliferative effect on the five monolayer CRC cell lines (SW480, LoVo, HCT-8, HCT-116 and SW620) or the hepatocarcinoma cell line (HepG2). However, CAP exerted marked anti-tumor activities on each of the CRC cell lines in the co-culture models containing both CRC and hepatocarcinoma cell lines, although its effect on the five CRC cell lines varied. Moreover, after pre-incubation of CAP with HepG2 cells, the culture media containing the active metabolites of CAP also showed an anti-tumor effect on the five CRC cell lines, indicating the crucial role of hepatic cells in the activation of CAP. CONCLUSION: The simple and cost­effective co-culture models with both CRC and hepatocarcinoma cells could mimic the in vivo process of a prodrug dependent on metabolic conversion to active metabolites in the liver, providing a valuable strategy for evaluating the PK and PD characteristics of CAP-like prodrugs in vitro at the early stage of drug development.

The gut microbiota modulates responses to anti-PD-1 and chemotherapy combination therapy and related adverse events in patients with advanced solid tumors.

Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) have been widely used in treating different malignancies. Several studies have reported that the gut microbiota modulates the response and adverse events (AEs) to ICIs in melanoma, non-small cell lung cancer (NSCLC), renal cell cancer and hepatocellular carcinoma, but data on other cancer types and ICI combination therapy are limited. Methods: Stool samples were collected from patients with cancer who received anti-PD-1 and chemotherapy combination treatment and were analyzed by fecal metagenomic sequencing. The microbiota diversity and composition were compared between the responder (R) and non-responder (NR) groups and the AE vs. the non-AE (NAE) groups. In addition, associated functional genes and metabolic pathways were identified. Results: At baseline, the microbiota diversity of the groups was similar, but the genera Parabacteroides, Clostridia bacterium UC5.1_2F7, and Bifidobacterium dentium were enriched in the R group, whereas Bacteroides dorei and 11 species of Nocardia were enriched in the NR group. At 6 weeks, the beta diversity was significantly different between the R and NR groups. Further analysis found that 35 genera, such as Alipes, Parabacteroides, Phascolarctobacterium, Collinsella, Ruminiclostridium, Porphyromonas, and Butyricimonas and several genera of the Fibrobacteraceae family, were frequently distributed in the R group, whereas 17 genera, including Enterococcus, Lachnoclostridium, Hungatella, and Bilophila and several genera of the Pseudonocardiaceae and Beijerinckiaceae families, were more abundant in the NR group. A total of 66 and 52 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs (KOs) were significantly enriched in the R and NR groups, respectively. In addition, pathway analysis revealed functional differences in the gut microbacteria in the R group, including the enrichment of anabolic pathways and DNA damage repair (DDR) pathways. Dynamic comparisons of the bacterial composition at baseline, 6 weeks, and 12 weeks showed that the abundance of Weissella significantly increased in the R group at 6 weeks and the abundance of Fusobacterium and Anaerotruncus significantly increased in the NR group at 12 weeks. Linear discriminant analysis effect size analysis indicated that bacteria of Bacteroidetes, especially Bacteroides, were enriched in the NAE group, whereas flora of Firmcutes, such as Faecalibacterium prausnitzii, Bacteroides fragilis, and Ruminococcus lactaris, were enriched in the AE group. Conclusion: Beta diversity and differences in the gut microbiota modulated AEs and the response to anti-PD-1 blockade combined with chemotherapy, by regulating related anabolic and DDR pathways. Dynamic changes in the intestinal microbiome may predict the efficacy of PD-1 inhibitor-based therapy.

First-line PD-1/PD-L1 inhibitors plus chemotherapy versus bevacizumab plus chemotherapy for advanced non-squamous non-small cell lung cancer: A Bayesian network meta-analysis of randomized controlled trials.

Chemotherapy in combination with immune checkpoint inhibitor (ICI) or bevacizumab has demonstrated a superior effect for non-squamous non-small cell lung cancer (NS-NSCLC). There are still few randomized controlled trials (RCTs) investigating the differences between ICI plus chemotherapy (ICI-chemotherapy) and bevacizumab plus chemotherapy (Bev-chemotherapy) in first-line treatment of NS-NSCLC. We identified RCTs in databases and conference abstracts presented at international conferences by Sep 1, 2021. Bayesian network meta-analysis was performed using randomized effect consistency model to estimate hazard ratio (HR) and odds ratio (OR). The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade ≥ 3 treatment-related adverse events (TRAEs). Fifteen RCTs (17 articles) of 6561 advanced NS-NSCLC patients receiving ICI-chemotherapy, Bev-chemotherapy, or chemotherapy at first-line were eligible for analysis. NMA results showed that first-line ICI-chemotherapy prolonged OS (HR 0.79, 0.66-0.94) in patients with advanced NS-NSCLC compared with Bev-chemotherapy, while no differences were in PFS, ORR, and grade ≥ 3 TRAEs (p > 0.05). Ranking plots suggested that ICI-chemotherapy had the most probability to offer the best OS (probability 0.993), PFS (probability 0.658), and ORR (probability 0.565), and Bev-chemotherapy had the most risks of grade ≥ 3 TRAEs (probability 0.833). Therefore, our findings showed that first-line ICI-chemotherapy was associated with better OS than Bev-chemotherapy in patients with advanced NS-NSCLC, and more clinical trials are warranted to confirm these results.

Distribution and identification of Mycobacterium tuberculosis lineage in Kashgar prefecture.

OBJECTIVES: Kashgar prefecture is an important transportation and trade hub with a high incidence of tuberculosis. The following study analyzed the composition and differences in Mycobacterium tuberculosis (M.tb) lineage and specific tags to distinguish the lineage of the M.tb in Kashgar prefecture, thus providing a basis for the classification and diagnosis of tuberculosis in this area. METHODS: Whole-genome sequencing (WGS) of 161 M.tb clinical strains was performed. The phylogenetic tree was constructed using Maximum Likelihood (ML) based on single nucleotide polymorphisms (SNPs) and verified through principal component analysis (PCA). The composition structure of M.tb in different regions was analyzed by combining geographic information. RESULTS: M.tb clinical strains were composed of lineage 2 (73/161, 45.34%), lineage 3 (52/161, 32.30%) and lineage 4 (36/161, 22.36%). Moreover, the 3 lineages were subdivided into 11 sublineages, among which lineage 2 included lineage 2.2.2/Asia Ancestral 1 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 2 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 3 (18/73, 24.66%), and lineage 2.2.1-Modern Beijing (39/73, 53.42%). Lineage 3 included lineage 3.2 (14/52, 26.92%) and lineage 3.3 (38/52, 73.08%), while lineage 4 included lineage 4.1 (3/36, 8.33%), lineage 4.2 (2/36, 5.66%), lineage 4.4.2 (1/36, 2.78%), lineage 4.5 (28/36, 77.78%) and lineage 4.8 (2/36, 5.66%), all of which were consistent with the PCA results. One hundred thirty-six markers were proposed for discriminating known circulating strains. Reconstruction of a phylogenetic tree using the 136 SNPs resulted in a tree with the same number of delineated clades. Based on geographical location analysis, the composition of Lineage 2 in Kashgar prefecture (45.34%) was lower compared to other regions in China (54.35%-90.27%), while the composition of Lineage 3 (32.30%) was much higher than in other regions of China (0.92%-2.01%), but lower compared to the bordering Pakistan (70.40%). CONCLUSION: Three lineages were identified in M.tb clinical strains from Kashgar prefecture, with 136 branch-specific SNP. Kashgar borders with countries that have a high incidence of tuberculosis, such as Pakistan and India, which results in a large difference between the M.tb lineage and sublineage distribution in this region and other provinces of China.

Effects of Mycobacterium tuberculosis lineages and regions of difference (RD) virulence gene variation on tuberculosis recurrence.

Background: China ranks second in the incidence of tuberculosis (TB), and the virulence and infectivity of Mycobacterium tuberculosis (M.tb) in different lineages are different. The variation of virulence genes in the M.tb regions of difference (RD) may be the reason for differences in pathogenicity. Studying the relationship between virulence gene mutations in the RD region of clinical strains of M.tb and TB relapse can provide basic data for the study of TB prevention and control. Methods: A total of 155 M.tb clinical strains were collected in Kashgar Prefecture. Whole-genome sequencing (WGS) was conducted, and mutations in virulence genes in the M.tb RD region were analyzed. The maximum likelihood method was implemented using IQ-TREE software. Logistic regression was used to analyze the relationship between lineage, RD region virulence gene variation, and patient relapse. Results: The 155 strains of M.tb in Kashgar Prefecture belong to 3 M.tb lineages: L2 (45.80%), L3 (32.90%), and L4 (21.30%). In relapsed patients, L2 (70.83%, 17/24) was significantly higher than the other lineages (29.17%, 7/24; P<0.05). Relapse was significantly correlated with L2 [odds ratio (OR) =3.505; 95% confidence interval (CI): 1.341-9.158; P=0.011]. In the virulence genes of the RD region, g.4357804 (T→G, OR =4.278; 95% CI: 1.594-11.481; P=0.004), g.4359653 (C→T, OR =3.356; 95% CI: 1.303-8.644; P=0.012), and g.2627618 (C→A, OR =2.676; 95% CI: 1.101-6.502; P=0.030) mutations were significantly associated with patient relapse. The mutation frequencies of g.4357804, g.4359653, and g.2627618 in L2 were significantly higher than those in the non-L2 group (P<0.05). Conclusions: Patients infected with L2 are more prone to relapse, and RD region virulence gene variation is an important factor for the strong pathogenicity and easy relapse after infection associated with L2.

Temporal single-cell tracing reveals clonal revival and expansion of precursor exhausted T cells during anti-PD-1 therapy in lung cancer.

Anti-PD-1 treatment has shown unprecedented clinical success in the treatment of non-small-cell lung cancer (NSCLC), but the underlying mechanisms remain incompletely understood. Here, we performed temporal single-cell RNA and paired T-cell receptor sequencing on 47 tumor biopsies from 36 patients with NSCLC following PD-1-based therapies. We observed increased levels of precursor exhausted T (Texp) cells in responsive tumors after treatment, characterized by low expression of coinhibitory molecules and high expression of GZMK. By contrast, nonresponsive tumors failed to accumulate Texp cells. Our data suggested that Texp cells were unlikely to be derived from the reinvigoration of terminally exhausted cells; instead, they were accumulated by (1) local expansion and (2) replenishment by peripheral T cells with both new and pre-existing clonotypes, a phenomenon we named clonal revival. Our study provides insights into mechanisms underlying PD-1-based therapies, implicating clonal revival and expansion of Texp cells as steps to improve NSCLC treatment.

Prognostic Value of the Pretreatment Lung Immune Prognostic Index in Advanced Small Cell Lung Cancer Patients Treated With First-Line PD-1/PD-L1 Inhibitors Plus Chemotherapy.

BACKGROUND: Lung immune prognostic index (LIPI) refers to a biomarker combining derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH). Its prognostic effect on advanced small cell lung cancer (SCLC) patients receiving programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors plus chemotherapy as first-line treatment remains unclear. Our research investigated the relationship between pretreatment LIPI and the prognosis of patients receiving first-line PD-1/PD-L1 inhibitors plus chemotherapy. METHODS: Advanced SCLC patients receiving PD-1/PD-L1 inhibitors plus chemotherapy as first-line treatment from Jan 2015 to Oct 2020 were included. Based on the values of dNLR and LDH, the study population was divided into two groups: LIPI good and LIPI intermediate/poor. The Kaplan-Meier method was used to compute the median survival time and the log-rank test was used to compare the two groups. Univariate and multivariate analyses were used to examine the correlation between the pretreatment LIPI and clinical outcomes. RESULTS: One hundred patients were included in this study, of which, 64% were LIPI good (dNLR < 4.0 and LDH < 283 U/L), 11% were LIPI poor (dNLR ≥ 4.0 and LDH ≥ 283 U/L), and the remaining 25% were LIPI intermediate. The LIPI good group had better progression-free survival (PFS) (median: 8.4 vs 4.7 months, p = 0.02) and overall survival (OS) (median: 23.8 vs 13.3 months, p = 0.0006) than the LIPI intermediate/poor group. Multivariate analysis showed that pretreatment LIPI intermediate/poor was an independent risk factor for OS (HR: 2.34; 95%CI, 1.13, 4.86; p = 0.02). Subgroup analysis showed that pretreatment LIPI good was associated with better PFS and OS in males, extensive disease (ED), PD-1 inhibitor treatment, smokers, and liver metastasis (p < 0.05). CONCLUSIONS: Pretreatment LIPI could serve as a prognostic biomarker for advanced SCLC patients receiving first-line PD-1/PD-L1 inhibitors plus chemotherapy.

The Involvement of Macrophage Colony Stimulating Factor on Protein Hydrolysate Injection Mediated Hematopoietic Function Improvement.

Protein hydrolysate injection (PH) is a sterile solution of hydrolyzed protein and sorbitol that contains 17 amino acids and has a molecular mass of 185.0-622.0 g/mol. This study investigated the effect of PH on hematopoietic function in K562 cells and mice with cyclophosphamide (CTX)-induced hematopoietic dysfunction. In these myelosuppressed mice, PH increased the number of hematopoietic cells in the bone marrow (BM) and regulated the concentration of several factors related to hematopoietic function. PH restored peripheral blood cell concentrations and increased the numbers of hematopoietic stem cells and progenitor cells (HSPCs), B lymphocytes, macrophages, and granulocytes in the BM of CTX-treated mice. Moreover, PH regulated the concentrations of macrophage colony stimulating factor (M-CSF), interleukin (IL)-2, and other hematopoiesis-related cytokines in the serum, spleen, femoral condyle, and sternum. In K562 cells, the PH-induced upregulation of hematopoiesis-related proteins was inhibited by transfection with M-CSF siRNA. Therefore, PH might benefit the BM hematopoietic system via the regulation of M-CSF expression, suggesting a potential role for PH in the treatment of hematopoietic dysfunction caused by cancer therapy.

Triple-Endobutton and clavicular hook: A propensity score matching analysis.

We retrospectively analyzed the clinical data of 635 patients with acute acromioclavicular dislocation, who underwent surgery in our hospital between May 2014 and June 2020. Patients were divided into group A (clavicular hook plate) and group B (Triple-Endobutton plates via double-incision). The propensity score analysis using one to one match was performed for comparisons. We obtained 292 matched patients' data. The matched preoperative clinical characteristics were a balance between the two groups. All clinical parameters showed insignificant differences (P > 0.05). Compared with group A, group B has longer operative time (P < 0.001) and more blood loss (P < 0.001); however, the mean incision length (P < 0.001) and length of hospitalization (P < 0.001) were shorter in group B than in the group A. The mean VAS in group B were significantly lower than in group A at each time point (P < 0.001), and the UCLA shoulder score was higher in the group B. The CMS scores were also higher in group B than in group A, including before removal and 12 weeks after removal (P < 0.001). The clinical efficacy of the double-incision Triple-Endobutton plate is better than the clavicular hook plate technology, and achieves anatomical reduction by reconstructing coracoclavicular ligament.

Real-World Efficacy and Safety of Anlotinib With and Without Immunotherapy in Advanced Non-Small Cell Lung Cancer.

AIMS: Combination of anti-angiogenesis therapy and immunotherapy has showed synergistic effects in non-small cell lung cancer (NSCLC). The aim of this retrospective study was to investigate the efficacy and safety of anlotinib with and without immunotherapy in NSCLC. METHODS: Pathologically confirmed NSCLC patients (stage IIIB-IV) receiving anlotinib between November 2018 and February 2020 were enrolled for retrospective analysis. The outcomes and safety of overall patients were evaluated, and the efficacies of anlotinib plus immunotherapy and anlotinib alone was compared. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 80 patients (median age: 62 years, range: 29-86 years) were included. Overall median PFS was 4.3 months (95% confidence interval (CI): 2.7-5.9 months). In univariate analysis, patients without EGFR mutation, previous EGFR target therapy, and brain metastasis had significantly longer PFS. Cox regression analysis showed that only brain metastasis was an independent predictor of PFS. The median PFS of patients receiving anlotinib plus immunotherapy was slightly longer than that of patients receiving anlotinib alone (4.2 vs 3.1 months); however, the difference was not statistically significant. A tendency of longer median PFS was observed in patients with adenocarcinoma, EGFR wild type, stage IV, no liver metastasis, former smoker, ≥2 previous treatment lines, no previous VEGF or EGFR target therapies in anlotinib plus immunotherapy group. Treatments with anlotinib alone or anlotinib plus immunotherapy were well tolerable. The most common adverse events were fatigue, decreased hemoglobin count, hypertension, hand-foot syndrome, oral mucositis and hoarseness. CONCLUSION: Anlotinib is well tolerable and effective in advanced NSCLC patients. Brain metastasis is an independent predictor of PFS in NSCLC patients receiving anlotinib. Future prospective studies with larger sample size and extended follow-up are needed to confirm the clinical benefit in NSCLC patients treated with anlotinib combined with immunotherapy.

Predicting disease progression in advanced non-small cell lung cancer with circulating neutrophil-derived and platelet-derived microparticles.

BACKGROUND: Microparticles (MPs) are extracellular vesicles that are associated with cancer development and progression. Advanced non-small cell lung cancer (NSCLC) still shows disease progression after multiple lines of treatment. Therefore, the objective of this study was to explore the correlation between circulating MPs and disease progression in advanced NSCLC, and to find a new method for concise and rapid determination of disease progression. METHODS: Patients with advanced NSCLC admitted to hospital between October 2019 and October 2020 were included and divided into objective remission (OR) and progressive disease (PD) groups. The morphology of MPs was observed using transmission electron microscopy. The circulating total MPs, neutrophil MPs (NMPs), and platelet MPs (PMPs) before and after treatment were detected by flow cytometry, and a predictive model for disease progression in advanced NSCLC was developed. RESULTS: Eighty-six patients were included; 60 in the OR group and 26 in the PD group. There was no significant difference in total MPs, NMPs, or PMPs at baseline between the two groups. After treatment, total MPs, NMPs, and PMPs were significantly higher in the PD than those in the OR group. Multivariate regression analysis showed that post-treatment NMPs≥160 events/µL(OR,3.748;95%CI,1.147-12.253,p = 0.029), PMPs≥80 events/µL(OR,10.968;95%CI,2.973-40.462,p < 0.0001) and neutrophil/lymphocyte ratio (NLR) ≥3.3 (OR,4.929;95%CI,1.483-16.375,p = 0.009) were independently associated with progression of advanced NSCLC. Post-treatment NMPs and PMPs combined with NLR were used to build a predictive model for progression of advanced NSCLC. The area under the curve was 0.825 (95%CI,0.715-0.934, p < 0.0001), optimal cut-off value was 16, sensitivity was 80.8%, and specificity was 88.3%. CONCLUSION: NMPs and PMPs are associated with progression of advanced NSCLC. The predictive model for progression of advanced NSCLC, established combining NMPs, PMPs, and NLR, can screen out 80.8% of patients with PD. This is helpful for real-time accurate, concise and rapid assessment of disease progression and timely adjustment of drug therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800020223 . Registered 20 December 2018, http://www.chictr.org.cn/index.aspx .

Association of the pretreatment lung immune prognostic index with survival outcomes in advanced gastric cancer patients treated with immune checkpoint inhibitors.

PURPOSE: Recently, the lung immune prognostic index (LIPI) is considered to be associated with outcomes in multiple solid tumors treated with immune checkpoint inhibitors (ICIs). We sought to determine whether LIPI has the same predictive effect in advanced gastric cancer (AGC). METHODS: The clinical data of a real-world, retrospective cohort of AGC patients treated with ICIs were retrospectively analyzed. Based on pre-treatment dNLR>3 and LDH>250 U/L, patients were assigned to one of three groups: good (0 factors), intermediate (1 factor), and poor (2 factors). The subjects were divided into two groups: LIPI-good and LIPI-intermediate/poor groups. Then, the disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were compared between these two groups. RESULTS: Finally, 120 patients were enrolled in the study, for both the good group and intermediate/poor group, DCR was 69.5% vs. 42.1% (P = 0.004). In a multivariate analysis, the LIPI-intermediate/poor group was associated with progressive disease, with an OR of 2.57 (95% CI, 1.05-6.30; P = 0.039). Patients with a good LIPI score had a longer survival compared with those with intermediate/poor scores, with an estimated median OS of 10.4 vs. 3.9 months (HR = 2.59, 95% CI: 1.69-3.98) and a median PFS of 7.7 vs. 2.1 months (HR=2.95, 95% CI:1.91-4.56). Multivariate analysis indicated that the intermediate/poor LIPI was independently associated with OS (HR: 2.32, 95% CI: 1.44-3.72) and PFS (HR: 2.48, 95% CI: 1.53-4.03). CONCLUSIONS: These data are the first to suggest that the pretreatment LIPI was well correlated with the outcomes of patients with AGC treated with ICIs.

HOXB5 promotes the progression of breast cancer through wnt/beta-catenin pathway.

OBJECTIVE: The present study was designed to explore the function of HOXB5 in breast cancer and related signaling pathway. METHODS: Breast cancer tissues and non-cancerous tissues were collected from 82 cases who were pathologically diagnosed with breast cancer. The mRNA level of HOXB5 was detected via quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was adopted to analyze the association of HOXB5 with clinical features. The viability, migration and invasion of breast cancer cells were detected through MTT and Transwell assays, respectively. Protein analysis was performed adopting western blot analysis. RESULTS: HOXB5 expression was increased in breast cancer tissues and cells, and showed positive correlation with tumor size (P = 0.028), TNM stage (P = 0.048), and lymph node metastasis (P = 0.002). Losing HOXB5 expression suppressed clone formation, proliferation, migration and invasion of breast cancer cells. The knockdown of HOXB5 significantly inactivated wnt/ß-catenin pathway. Furthermore, wnt/ß-catenin pathway had the potential to neutralize the oncogenic function of HOXB5 in breast cancer. CONCLUSION: HOXB5 may be involved in the invasive progression of breast cancer. The function of HOXB5 in breast cancer was mediated by wnt/ß-catenin pathway.