A novel nomogram based on the number of positive lymph nodes can predict the overall survival of patients with pancreatic head cancer after radical surgery.

BACKGROUND: This study aimed to construct a novel nomogram based on the number of positive lymph nodes to predict the overall survival of patients with pancreatic head cancer after radical surgery. MATERIALS AND METHODS: 2271 and 973 patients in the SEER Database were included in the development set and validation set, respectively. The primary clinical endpoint was OS (overall survival). Univariate and multivariate Cox regression analyses were used to screen independent risk factors of OS, and then independent risk factors were used to construct a novel nomogram. The C-index, calibration curves, and decision analysis curves were used to evaluate the predictive power of the nomogram in the development and validation sets. RESULTS: After multivariate Cox regression analysis, the independent risk factors for OS included age, tumor extent, chemotherapy, tumor size, LN (lymph nodes) examined, and LN positive. A nomogram was constructed by using independent risk factors for OS. The C-index of the nomogram for OS was 0.652 [(95% confidence interval (CI): 0.639-0.666)] and 0.661 (95%CI: 0.641-0.680) in the development and validation sets, respectively. The calibration curves and decision analysis curves proved that the nomogram had good predictive ability. CONCLUSIONS: The nomogram based on the number of positive LN can effectively predict the overall survival of patients with pancreatic head cancer after surgery.

CCL19-producing fibroblasts promote tertiary lymphoid structure formation enhancing anti-tumor IgG response in colorectal cancer liver metastasis.

Tertiary lymphoid structures (TLSs) are associated with enhanced immunity in tumors. However, their formation and functions in colorectal cancer liver metastasis (CRLM) remain unclear. Here, we reveal that intra- and peri-tumor mature TLSs (TLS+) are associated with improved clinical outcomes than TLS- tumors. Using single-cell-RNA-sequencing and spatial-enhanced-resolution-omics-sequencing (Stereo-seq), we reveal that TLS+ tumors are enriched with IgG+ plasma cells (PCs), while TLS- tumors are characterized with IgA+ PCs. By generating TLS-associated PC-derived monoclonal antibodies in vitro, we show that TLS-PCs secrete tumor-targeting antibodies. As the proof-of-concept, we demonstrate the anti-tumor activities of TLS-PC-mAb6 antibody in humanized mouse model of colorectal cancer. We identify a fibroblast lineage secreting CCL19 that facilitates lymphocyte trafficking to TLSs. CCL19 treatment promotes TLS neogenesis and prevents tumor growth in mice. Our data uncover the central role of CCL19+ fibroblasts in TLS formation, which in turn generates therapeutic antibodies to restrict CRLM.

[Land Use Change Driving and Optimization of Carbon Budget in Hangzhou Metropolitan Area].

As climate change, such as global warming, has become a global environmental issue, clarifying the mechanism driving the carbon budget based on land use change has become an inevitable path to realize the "double carbon" goal. Based on the land use change characteristics in the Hangzhou Metropolitan Area from 1995 to 2020, this study employed the inventory accounting method, concentration index, and panel regression models to investigate the driving mechanisms of carbon budget dynamics influenced by land use changes. Moreover, the study utilized a "scenario-actor" policy analysis framework to propose low-carbon strategies through the integration of land use management within territorial spatial planning. The research findings were as follows： ① The carbon source capacity in the study area significantly surpassed its carbon sink capacity. The overall carbon budget concentration index had yet to exceed the 0.4 "alert threshold," with spatial concentration levels as follows： Hangzhou > Huangshan > Shaoxing > Quzhou > Jiaxing ≈ Huzhou. ② For croplands, larger areas and greater shape regularity contributed to a reduction in carbon budgets. Conversely, for constructed lands, expansive areas and increased fragmentation intensified the carbon budget levels, primarily driven by other urban land categories. ③ An increased proportion of croplands and higher land use heterogeneity promoted spatial equilibrium in carbon budgets, whereas the larger coverage and fragmentation of industrial and other urban lands led to an uneven spatial distribution of carbon budgets. ④ Low-carbon optimization of territorial space needs to adjust for the structure and form of carbon source functional land use as a key driver. At the policy implementation level, the central government and urban residents demonstrated strong support for low-carbon territorial control. However, cooperation from local governments, enterprises, and rural residents was suboptimal, necessitating complementary policies for effective guidance. This study holds practical significance for enhancing land use efficiency and promoting low-carbon urban development.

[Research progress on effect evaluation and application status of acupoint drug delivery].

Acupoint drug delivery is a traditional external therapy of traditional Chinese medicine(TCM). Guided by the meridian and collateral theory in TCM, it applies medications to the skin at acupoints, exerting a dual therapeutic effect by stimulating the acupoints and the conduction of meridians. Acupoint drug delivery is widely used in clinical practice. Different from traditional oral admi-nistration and injection, it absorbs medications through the skin, effectively avoiding the first-pass effect of drugs and the toxic side effects caused by injection. Acupoint selection and transdermal drug absorption are pivotal factors affecting the efficacy of acupoint drug delivery. Recent research on acupoint drug delivery mainly focuses on the evaluation of clinical efficacy, yet the systematic investigations on acupoint selection and pharmacodynamic factors are scarce. This study reviews the mechanism, efficacy evaluation and application status of acupoint drug delivery. It integrates the theory of TCM with modern medicine to explore the mechanism of acupoint drug delivery, evaluate its clinical efficacy, and assess the transdermal penetration in vivo and in vitro. The application status of acupoint drug delivery is also summarized, including the selection of acupoints, application dosage form, application time and the absorption of acupoints. This review aims to offer insights and references for the research, development and clinical application of acupoint drug delivery products.

Determination of contamination, source, and risk of potentially toxic metals in fine road dust in a karst region of Southwest China.

Understanding the pollution situation of potentially toxic metals (PTMs) in fine road dust (FRD) in emerging industrialized cities and identifying priority control factors is crucial for urban environmental management, resident health protection, and pollution control. This study conducted a comprehensive investigation on PTMs pollution in FRD in Zunyi, a representative emerging industrialized city in the karst region of southwestern China. The average contents of Ni, Cr, Mn, Cu, Zn, Ba, Pb, V, and Co in the FRD were 43.2, 127.0, 1232.1, 134.4, 506.6, 597.8, 76.1, 86.8, and 16.2 mg kg-1, respectively, which were obviously higher than the corresponding background levels of the local soil except for V and Co. The comprehensive pollution level of the determined PTMs in the FRD was very high, primarily caused by Zn and Cu. The sources of PTMs in Zunyi FRD were traffic, industrial, construction, and natural sources, accounting for 38.0, 23.7, 21.9, and 16.4% of the total PTMs content, respectively. The PTMs in Zunyi FRD exhibited a low to moderate overall ecological risk level, mainly contributed by Cu and traffic source. The cancer risks of PTMs in Zunyi FRD were high for all populations. The non-carcinogenic risk of PTMs in Zunyi FRD was acceptable for adults, but cannot be ignored for children. According to the source-specific probabilistic health risk estimation results, the priority control source is industrial source and the priority control PTM is Cr. Local governments need to give more attention to the carcinogenic risks and health hazards posed by PTMs in the FRD.

Exploring the environmental risks and seasonal variations of potentially toxic elements (PTEs) in fine road dust in resource-based cities based on Monte Carlo simulation, geo-detector and random forest model.

The environmental pollution caused by mineral exploitation and energy consumption poses a serious threat to ecological security and human health, particularly in resource-based cities. To address this issue, a comprehensive investigation was conducted on potentially toxic elements (PTEs) in road dust from different seasons to assess the environmental risks and influencing factors faced by Datong City. Multivariate statistical analysis and absolute principal component score were employed for source identification and quantitative allocation. The geo-accumulation index and improved Nemerow index were utilized to evaluate the pollution levels of PTEs. Monte Carlo simulation was employed to assess the ecological-health risks associated with PTEs content and source orientation. Furthermore, geo-detector and random forest analysis were conducted to examine the key environmental variables and driving factors contributing to the spatiotemporal variation in PTEs content. In all PTEs, Cd, Hg, and Zn exhibited higher levels of content, with an average content/background value of 3.65 to 4.91, 2.53 to 3.34, and 2.15 to 2.89 times, respectively. Seasonal disparities were evident in PTEs contents, with average levels generally showing a pattern of spring (winter) > summer (autumn). PTEs in fine road dust (FRD) were primarily influenced by traffic, natural factors, coal-related industrial activities, and metallurgical activities, contributing 14.9-33.9 %, 41.4-47.5 %, 4.4-8.3 %, and 14.2-29.4 % to the total contents, respectively. The overall pollution and ecological risk of PTEs were categorized as moderate and high, respectively, with the winter season exhibiting the most severe conditions, primarily driven by Hg emissions from coal-related industries. Non-carcinogenic risk of PTEs for adults was within the safe limit, yet children still faced a probability of 4.1 %-16.4 % of unacceptable risks, particularly in summer. Carcinogenic risks were evident across all demographics, with children at the highest risk, mainly due to Cr and smelting industrial sources. Geo-detector and random forest model indicated that spatial disparities in prioritized control elements (Cr and Hg) were primarily influenced by particulate matter (PM10) and anthropogenic activities (industrial and socio-economic factors); variations in particulate matter (PM10 and PM2.5) and meteorological factors (wind speed and precipitation) were the primary controllers of seasonal disparities of Cr and Hg.

Analysis of clinical features and prognostic factors in Takayasu arteritis involving pulmonary hypertension: A retrospective study.

BACKGROUND: Multiple takayasu arteritis (TA) is a chronic nonspecific large to medium vasculitis disease that mainly accumulates the aorta and its branches. Pulmonary vascular disease is often seen as stenosis and occlusion, and patients may show no moderate to severe pulmonary hypertension (PH). This study aims to summarize the clinical characteristics and analysis of prognostic factors in patients with PH caused by TA. METHODS: Patients diagnosed with aortitis involving the pulmonary artery by pulmonary arteriography or pulmonary artery and total aortic computed tomography arteriography (CTA). All patients underwent detailed clinical assessment, laboratory data collection, and analysis of imaging data. Patients were followed up and factors affecting the prognosis of the pulmonary arteries were analyzed. RESULTS: Most of the patients' complaints were chest tightness, shortness of breath, decreased activity tolerance, hemoptysis and chest pain. 56.90% of the patients were in at the time of admission. Echocardiographic estimation of pulmonary artery systolic pressure was 90.39 ±â€…22.87 mm Hg. In terms of laboratory tests, 39.66%% of the patients had elevated C-reactive protein and erythrocyte sedimentation rate, and amino-terminal natriuretic peptide precursor on admission. In terms of imaging, all patients had pulmonary artery involvement, which was combined with aortic involvement in 31.03%. Nuclide lung perfusion/ventilation imaging of the patients revealed multiple perfusion defects/absences in the segmental and subsegmental distribution of the lungs. Univariate Cox regression model analysis suggested that patients' WHO functional class at admission, age ≧ 51 years at the time of consultation, and amino-terminal natriuretic peptide precursor ≧ 3500 pg/mL were factors affecting the prognosis. Further multifactorial Cox regression model analysis suggested amino-terminal natriuretic peptide precursor ≧ 3500 pg/mL was an independent predictor of poor prognosis with a hazard ratio (HR) value of 5.248. CONCLUSION: Electrocardiogram and echocardiogram may suggest an increased right heart load; some patients have elevated serum inflammatory indexes. Characteristic imaging manifestations include widening of the main pulmonary artery, multiple pulmonary segmental and subsegmental stenoses.

The FGF6 amplification mutation plays an important role in the progression and treatment of malignant meningioma.

Meningioma is a benign tumor with slow growth and long course. However, patients with recurrent malignant meningioma still face a lack of effective treatment. Here, we report a rare case of primary mediastinal malignant meningioma with lung and bone metastases, who benefited from the treatment of apatinib (≥33 months) and anlotinib (until the publication date). Retrospective molecular analysis revealed the frequent amplification of FGF6 in primary and metastatic lesions. Then we constructed the FGF6 over-expressed IOMM-LEE and CH157MN malignant meningioma cell lines, and in vitro and vivo experiments showed that overexpression of FGF6 can promote the proliferation, migration and invasion of malignant meningioma cells. Based on the Western analysis, we revealed that FGF6 can promote the phosphorylation of FGFR, AKT, and ERK1/2, which can be inhibited by anlotinib. Together, we were the first to verify that overexpression of FGF6 promotes the progression of malignant meningiomas by activating FGFR/AKT/ERK1/2 pathway and pointed out that anlotinib may effectively inhibit the disease progression of patients with FGF6 amplification.

CircPDE5A-encoded novel regulator of the PI3K/AKT pathway inhibits esophageal squamous cell carcinoma progression by promoting USP14-mediated de-ubiquitination of PIK3IP1.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal tumor and has become an important global health problem. The PI3K/AKT signaling pathway plays a key role in the development of ESCC. CircRNAs have been reported to be involved in the regulation of the PI3K/AKT pathway, but the underlying mechanisms are unclear. Therefore, this study aimed to identify protein-coding circRNAs and investigate their functions in ESCC. METHODS: Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. Thereafter, LC-MS/MS was used to identify circPDE5A-encoded novel protein PDE5A-500aa. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circPDE5A and PDE5A-500aa in ESCC. Lastly, circRNA-loaded nanoplatforms were constructed to investigate the therapeutic translation value of circPDE5A. RESULTS: We found that circPDE5A expression was down-regulated in ESCC cells and tissues and that it was negatively associated with advanced clinicopathological stages and poorer prognosis in ESCC. Functionally, circPDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding PDE5A-500aa, a key regulator of the PI3K/AKT signaling pathway in ESCC. Mechanistically, PDE5A-500aa interacted with PIK3IP1 and promoted USP14-mediated de-ubiquitination of the k48-linked polyubiquitin chain at its K198 residue, thereby attenuating the PI3K/AKT pathway in ESCC. In addition, Meo-PEG-S-S-PLGA-based reduction-responsive nanoplatforms loaded with circPDE5A and PDE5A-500aa plasmids were found to successfully inhibit the growth and metastasis of ESCC in vitro and in vivo. CONCLUSION: The novel protein PDE5A-500aa encoded by circPDE5A can act as an inhibitor of the PI3K/AKT signaling pathway to inhibit the progression of ESCC by promoting USP14-mediated de-ubiquitination of PIK3IP1 and may serve as a potential target for the development of therapeutic agents.

Controlling Nutritional Status (CONUT) Score is Associated with Overall Survival in Patients with Hepatocellular Carcinoma Treated with Conventional Transcatheter Arterial Chemoembolization: A Propensity Score Matched Analysis.

PURPOSE: This study aims to evaluate the prognostic value of controlling nutritional status (CONUT) score in determining the prognosis of patients with hepatocellular carcinoma (HCC) treated with conventional transcatheter arterial chemoembolization (cTACE). METHODS: This study retrospectively analyzed 936 patients who underwent cTACE for HCC between January 2012 and December 2018, and divided them into two groups based on their CONUT score. To balance the bias in baseline characteristics, propensity score matched (PSM) analysis was conducted. The Kaplan-Meier method was used to establish a cumulative survival curve, and the log-rank test was employed to determine differences in overall survival (OS) and progression-free survival (PFS) among the CONUT score groups. Furthermore, the Cox proportional hazard model was employed to assess the correlation between CONUT score and OS and PFS, whereby hazard ratios (HRs) and 95% confidence intervals (95% CIs) were computed. RESULTS: Before PSM, the median OS for the low (≤ 3) and high (≥ 4) CONUT group (558 vs. 378 patients) was 21.7 and 15.6 months, respectively, and the median PFS was 5.7 and 5 months. Following PSM, both the low and high CONUT score groups comprised 142 patients. The low CONUT score group exhibited a significantly longer OS compared to the high CONUT score group, as determined by the log-rank test (median OS 22.2 vs. 17.0 months, P = 0.014). No significant association was observed between CONUT group and PFS (median PFS 6.4 vs. 4.7 months, log-rank test, P = 0.121). Cox proportional hazard regression analysis revealed that a CONUT score of ≥ 4 was an independent risk factor for OS in patients with HCC who underwent cTACE (HR = 1.361; 95% CI: 1.047-1.771; P = 0.022). These findings were consistent across most subgroup analyses. CONCLUSION: A high CONUT score has been found to be a prognostic factor for poorer OS in patients with HCC who underwent cTACE. LEVEL OF EVIDENCE: Level 3, Non-randomized controlled cohort.

Functional knee phenotypes appear to be more suitable for the Chinese OA population compared with CPAK classification: A study based on 3D CT reconstruction models.

PURPOSE: The aim of this study was to investigate the distribution of coronal plane alignment of the knee (CPAK) classification and functional knee phenotypes in a Chinese osteoarthritis (OA) population and to compare different lower limb alignment targets according to the distribution characteristics to find suitable total knee arthroplasty (TKA) bone cut strategies for the Chinese OA patients. METHODS: The computed tomography (CT) images were retrospectively collected and the three-dimensional (3D) models were reconstructed from 434 Chinese OA patients, including 93 males and 341 females, with a mean age of 66.4 ± 9.3 years. Femoral mechanical angle (FMA), tibial mechanical angle (TMA) and mechanical hip-knee-ankle angle (mHKA) were measured on the 3D models. Arithmetic hip-knee-ankle angle (aHKA) was calculated using FMA plus TMA, and joint line obliquity was calculated as 180 + TMA-FMA. The CPAK according to MacDessi and the functional knee phenotypes according to Hirschmann were performed. In addition, the suitable TKA bone cut strategies were explored according to the phenotypes and based on the characteristics of different alignment targets, such as mechanical alignment, anatomic alignment (AA), kinematic alignment, restricted KA (rKA) and adjusted MA (aMA). Statistical differences were determined using the independent-samples t-test or the two independent-samples Wilcoxon test, with p < 0.05 considered statistically significant. RESULTS: The Chinese OA population showed a varus alignment tendency (mHKA = 172.1° ± 7.2°), to which the TMA was a major contributor (TMA = 84.7° ± 4.4° vs. FMA = 91.3° ± 3.2°). The mHKA was on average 3.9° more varus than the aHKA. A total of 140 functional knee phenotypes were found and 45.6% were concentrated in VARFMA3°-NEUFMA0° to VARTMA3°-NEUTMA0°. More than 70% of patients had different FMA and TMA phenotypes. There were 92.9% of CPAK distributed in types I to IV, with type I accounting for 53.9%. The FMA phenotypes were less changed if the aMA and rKA were chosen, and the TMA phenotypes were less changed if the AA and rKA were chosen. CONCLUSION: Compared with the CPAK, the functional knee phenotypes were more suitable for the Chinese OA population with a wide distribution and a varus tendency, and it seemed more appropriate to choose aMA and rKA as TKA alignment targets for resection. LEVEL OF EVIDENCE: Level Ⅲ.

Neuromuscular organoids model spinal neuromuscular pathologies in C9orf72 amyotrophic lateral sclerosis.

Hexanucleotide repeat expansions in the C9orf72 gene are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Due to the lack of trunk neuromuscular organoids (NMOs) from ALS patients' induced pluripotent stem cells (iPSCs), an organoid system was missing to model the trunk spinal neuromuscular neurodegeneration. With the C9orf72 ALS patient-derived iPSCs and isogenic controls, we used an NMO system containing trunk spinal cord neural and peripheral muscular tissues to show that the ALS NMOs could model peripheral defects in ALS, including contraction weakness, neural denervation, and loss of Schwann cells. The neurons and astrocytes in ALS NMOs manifested the RNA foci and dipeptide repeat proteins. Acute treatment with the unfolded protein response inhibitor GSK2606414 increased the glutamatergic muscular contraction 2-fold and reduced the dipeptide repeat protein aggregation and autophagy. This study provides an organoid system for spinal neuromuscular pathologies in ALS and its application for drug testing.

Th17 Cells Secrete TWEAK to Trigger Epithelial-Mesenchymal Transition and Promote Colorectal Cancer Liver Metastasis.

Liver metastasis is the leading cause of mortality in patients with colorectal cancer. Given the significance of both epithelial-mesenchymal transition (EMT) of tumor cells and the immune microenvironment in colorectal cancer liver metastasis (CRLM), the interplay between them could hold the key for developing improved treatment options. We employed multiomics analysis of 130 samples from 18 patients with synchronous CRLM integrated with external datasets to comprehensively evaluate the interaction between immune cells and EMT of tumor cells in liver metastasis. Single-cell RNA sequencing analysis revealed distinct distributions of nonmalignant cells between primary tumors from patients with metastatic colorectal cancer (mCRC) and non-metastatic colorectal cancer, showing that Th17 cells were predominantly enriched in the primary lesion of mCRC. TWEAK, a cytokine secreted by Th17 cells, promoted EMT by binding to receptor Fn14 on tumor cells, and the TWEAK-Fn14 interaction enhanced tumor migration and invasion. In mouse models, targeting Fn14 using CRISPR-induced knockout or lipid nanoparticle-encapsulated siRNA alleviated metastasis and prolonged survival. Mice lacking Il17a or Tnfsf12 (encoding TWEAK) exhibited fewer metastases compared with wild-type mice, while cotransfer of Th17 with tumor cells promoted liver metastasis. Higher TWEAK expression was associated with a worse prognosis in patients with colorectal cancer. In addition, CD163L1+ macrophages interacted with Th17 cells, recruiting Th17 via the CCL4-CCR5 axis. Collectively, this study unveils the role of immune cells in the EMT process and identifies TWEAK secreted by Th17 as a driver of CRLM. SIGNIFICANCE: TWEAK secreted by Th17 cells promotes EMT by binding to Fn14 on colorectal cancer cells, suggesting that blocking the TWEAK-Fn14 interaction may be a promising therapeutic approach to inhibit liver metastasis.

Impact of preoperative transcatheter arterial chemoembolization (TACE) on postoperative long-term survival in patients with nonsmall hepatocellular carcinoma: a propensity score matching analysis.

BACKGROUND: The purpose of this propensity score matching (PSM) analysis was to compare the effects of preoperative transcatheter arterial chemoembolization (TACE) and non-TACE on the long-term survival of patients who undergo radical hepatectomy. METHODS: PSM analysis was performed for 387 patients with hepatocellular carcinoma (HCC) (single > 3 cm or multiple) who underwent radical resection of HCC at our centre from January 2011 to June 2018. The patients were allocated to a preoperative TACE group (n = 77) and a non-TACE group (n = 310). The main outcome measures were progression-free survival (PFS) and overall survival (OS) since the treatment date. RESULTS: After PSM, 67 patients were included in each of the TACE and non-TACE groups. The median PFS times in the preoperative TACE and non-TACE groups were 24.0 and 11.3 months, respectively (p = 0.0117). The median OS times in the preoperative TACE and non-TACE groups were 41.5 and 29.0 months, respectively (p = 0.0114). Multivariate Cox proportional hazard regression analysis revealed that preoperative TACE (hazard ratio, 1.733; 95% CI, 1.168-2.570) and tumour thrombosis (hazard ratio, 0.323; 95% CI, 0.141-0.742) were independent risk factors significantly associated with OS. CONCLUSIONS: Preoperative TACE is related to improving PFS and OS after resection of HCC. Preoperative TACE and tumour thrombus volume were also found to be independent risk factors associated with OS.

Nrf2/HO-1 signaling activation alleviates cigarette smoke-induced inflammation in chronic obstructive pulmonary disease by suppressing NLRP3-mediated pyroptosis.

BACKGROUND: This study examined the effect of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway on chronic obstructive pulmonary disease (COPD) and the potential molecular mechanism. METHODS: A COPD mouse model was established by cigarette smoke exposure and administered with either ML385 or dimethyl fumarate (DMF). Airway resistance of mice was detected. IL-1ß and IL-6 levels in mice alveolar lavage fluid were examined by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining and immunohistochemical of lung tissues were utilized to detect lung injury and NLRP3 expression. DMF was used to treat COPD cell model constructed by exposing normal human bronchial epithelial (NHBE) cells to cigarette smoke extract. NHBE cells were transfected by NLRP3-expression vectors. Expression of proteins was detected by Western blot. RESULTS: COPD mice showed the enhanced airway resistance, the inactivated Nrf2/HO-1 pathway and the overexpressed NLRP3, Caspase-1 and GSDMD-N proteins in lung tissues, and the increased IL-1ß and IL-6 levels in alveolar lavage fluid. ML385 treatment augmented these indicators and lung injury in COPD mice. However, DMF intervention attenuated these indicators and lung injury in COPD mice. Nrf2/HO-1 pathway inactivation and overexpression of NLRP3, Caspase-1 and GSDMD-N proteins were observed in COPD cells. DMF intervention activated Nrf2/HO-1 pathway and down-regulated NLRP3, Caspase-1 and GSDMD-N proteins in COPD cells. However, NLRP3 overexpression abolished the effect of DMF on COPD cells. CONCLUSION: Nrf2/HO-1 pathway activation may alleviate inflammation in COPD by suppressing the NLRP3-related pyroptosis. Activating the Nrf2/HO-1 pathway may be an effective method to treat COPD.

Extended lymphadenectomy based on the TRIANGLE for pancreatic head cancer: a single-center experience.

BACKGROUND: This study was to compare the safety and efficacy of different lymphadenectomy methods in patients with pancreatic head cancer undergoing pancreaticoduodenectomy (PD). MATERIAL AND METHODS: A total of 150 patients were included in this study. Patients were divided into Group A (n = 79), Group B (n = 44), and Group C (n = 27) according to the different lymphadenectomy methods. The clinical endpoint was time to progression (TTP) and overall survival (OS). Postoperative complications of different lymphadenectomy methods were compared respectively. TTP and OS of the three groups were compared by Kaplan-Meier curves. RESULTS: There were no significant differences between the three groups in operative time (P = 0.300), death in the hospital (P = 0.253), postoperative hemorrhage (P = 0.863), postoperative pancreatic fistula (POPF) B/C (P = 0.306), bile leakage (P = 0.215), intestinal fistula (P = 0.177), lymphatic leakage (P = 0.267), delayed gastric emptying [(DGE) (P = 0.283)], ICU stay (P = 0.506), and postoperative hospital stay [(PHS) (P = 0.810)]. Median TTP in Groups B and C was significantly longer than in Group A (log-rank test, A vs B: P = 0.0005, A vs C: P = 0.0001). Median OS between the three groups has no statistical difference (P = 0.1546). CONCLUSIONS: Extended lymphadenectomy methods based on the TRIANGLE do not increase perioperative complications significantly and can effectively delay tumor progression in patients with pancreatic head cancer.

Single-cell RNA sequencing reveals the MIF-ACKR3 receptor-ligand interaction between iCAFs and tumor cells in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor of the gastrointestinal tract with a high morbidity and mortality rate. The heterogeneity of ESCC poses challenges in treatment and contributes to the poor prognosis of patients. Therefore, it is crucial to gain a better understanding of the tumor microenvironment (TME) heterogeneity and identify novel therapeutic targets. METHODS: To solve this problem, we performed a single-cell RNA sequencing (scRNA-seq) analysis of ESCC samples obtained from the GEO database. RESULTS: A total of 31,283 single cells were categorized into nine cell types, which included four non-immune cells (epithelial cells, endothelial cells, fibroblasts, schwann cells) and five immune cells (T cells, macrophages, mast cells, neutrophils, B cells). Our study revealed the presence of immunosuppressive tumor microenvironments in ESCC. We have also identified not only inflammatory cancer-associated fibroblast (iCAFs) and myofibroblastic cancer-associated fibroblasts (myCAFs) but also a subset of antigen presenting cancer-associated fibroblasts (apCAFs) which express high levels of HLA class II molecules in ESCC. Furthermore, our analysis of cell communication showed up-regulation of MIF-ACKR3 interaction between iCAFs and tumor cells in tumors compared to normal tissues. Finally, it was demonstrated that macrophage migration inhibitory factor (MIF) facilitates tumor cell migration and invasion through interacting with ACKR3 in vitro. CONCLUSIONS: This study exposes the features of the tumor microenvironment of ESCC via scRNA-seq and examines the dynamics of various cellular subpopulations, thus facilitating the identification of future therapeutic targets for ESCC.

Protocol for culturing and functionally manipulating planarian neoblasts using SiR-DNA-based flow cytometry.

Neoblasts are the only cells capable of proliferation in planarians. The traditional flow cytometry protocol using Hoechst inhibits the cell cycle. Here, we present a protocol for culturing and functionally manipulating planarian neoblasts using SiR-DNA-based flow cytometry. We describe steps for cell dissociation and staining, flow cytometry, and cell collection and culture. We then detail procedures for Nanoluciferase mRNA transfection. This protocol facilitates further investigations into the pluripotency and regeneration mechanisms within neoblasts. For complete details on the use and execution of this protocol, please refer to Lei et al.1.

Generation of two induced pluripotent stem cell lines from two sporadic amyotrophic lateral sclerosis patients.

Peripheral blood mononuclear cells were obtained from two patients diagnosed with amyotrophic lateral sclerosis (ALS), a 47-year-old female and a 45-year-old male. Induced pluripotent stem cells (iPSCs) were generated using a non-integrating SeV-based method, delivering the transcription factors OCT4, SOX2, c-MYC, and KLF4. These transgene-free iPSC lines exhibited typical pluripotent cell morphology, expressed pluripotency-associated markers, and had tri-lineage differentiation potential. Both iPSC lines were free of mycoplasma contamination and displayed normal karyotypes. The availability of these two cell lines provides a promising opportunity to use sporadic ALS models for investigating the intricate pathological mechanisms of ALS.