Trends in 5-year cancer survival disparities by race and ethnicity in the US between 2002-2006 and 2015-2019.

Racial and ethnic disparities persist in cancer survival rates across the United States, despite overall improvements. This comprehensive analysis examines trends in 5-year relative survival rates from 2002-2006 to 2015-2019 for major cancer types, elucidating differences among racial/ethnic groups to guide equitable healthcare strategies. Data from the SEER Program spanning 2000-2020 were analyzed, focusing on breast, colorectal, prostate, lung, pancreatic cancers, non-Hodgkin lymphoma, acute leukemia, and multiple myeloma. Age-standardized relative survival rates were calculated to assess racial (White, Black, American Indian/Alaska Native, Asian/Pacific Islander) and ethnic (Hispanic, Non-Hispanic) disparities, utilizing period analysis for recent estimates and excluding cases identified solely through autopsy or death certificates. While significant survival improvements were observed for most cancers, notable disparities persisted. Non-Hispanic Blacks exhibited the largest gain in breast cancer survival, with an increase of 5.2% points (from 77.6 to 82.8%); however, the survival rate remained lower than that of Non-Hispanic Whites (92.1%). Colorectal cancer survival declined overall (64.7-64.1%), marked by a 6.2% point drop for Non-Hispanic American Indian/Alaska Natives (66.3-60.1%). Prostate cancer survival declined across all races, with Non-Hispanic American Indian/Alaska Natives showing a decrease of 7.7% points (from 96.9 to 89.2%). Lung cancer, acute leukemia, and multiple myeloma showed notable increases across groups. Substantial racial/ethnic disparities in cancer survival underscore the notable need for tailored strategies ensuring equitable access to advanced treatments, particularly addressing significant trends in colorectal and pancreatic cancers among specific minority groups. Careful interpretation of statistical significance is warranted given the large dataset.

LIM domain only 7: a novel driver of immune evasion through regulatory T cell differentiation and chemotaxis in pancreatic ductal adenocarcinoma.

With advancements in genomics and immunology, immunotherapy has emerged as a revolutionary strategy for tumor treatment. However, pancreatic ductal adenocarcinoma (PDAC), an immunologically "cold" tumor, exhibits limited responsiveness to immunotherapy. This study aimed to address the urgent need to uncover PDAC's immune microenvironment heterogeneity and identify the molecular mechanisms driving immune evasion. Using single-cell RNA sequencing datasets and spatial proteomics, we discovered LIM domain only 7 (LMO7) in PDAC cells as a previously unrecognized driver of immune evasion through Treg cell enrichment. LMO7 was positively correlated with infiltrating regulatory T cells (Tregs) and dysfunctional CD8+ T cells. A series of in vitro and in vivo experiments demonstrated LMO7's significant role in promoting Treg cell differentiation and chemotaxis while inhibiting CD8+ T cells and natural killer cell cytotoxicity. Mechanistically, LMO7, through its LIM domain, directly bound and promoted the ubiquitination and degradation of Foxp1. Foxp1 negatively regulated transforming growth factor-beta (TGF-ß) and C-C motif chemokine ligand 5 (CCL5) expression by binding to sites 2 and I/III, respectively. Elevated TGF-ß and CCL5 levels contribute to Treg cell enrichment, inducing immune evasion in PDAC. Combined treatment with TGF-ß/CCL5 antibodies, along with LMO7 inhibition, effectively reversed immune evasion in PDAC, activated the immune response, and prolonged mouse survival. Therefore, this study identified LMO7 as a novel facilitator in driving immune evasion by promoting Treg cell enrichment and inhibiting cytotoxic effector functions. Targeting the LMO7-Foxp1-TGF-ß/CCL5 axis holds promise as a therapeutic strategy for PDAC. Graphical abstract revealing LMO7 as a novel facilitator in driving immune evasion by promoting Tregs differentiation and chemotaxis, inducing CD8+ T/natural killer cells inhibition.

In-Depth Investigation of Role of -BCO2 in the Degradation of Sulfamethazine by Metal-Free Biochar/Persulfate: The Mechanism of Occurrence of Nonradical Process.

The remediation of organic wastewater through advanced oxidation processes (AOPs) based on metal-free biochar/persulfate systems has been extensively researched. In this work, boron-doped alkali lignin biochar (BKC1:3) was utilized to activate peroxymonosulfate (PMS) for the removal of sulfamethazine (SMZ). The porous structure and substantial specific surface area of BKC1:3 facilitated the adsorption and thus degradation of SMZ. The XPS characterization and density functional theory (DFT) calculations demonstrated that -BCO2 was the main active site of BKC1:3, which dominated the occurrence of nonradical pathways. Neither quenching experiments nor EPR characterization revealed the generation of free radical signals. Compared with KC, BKC1:3 possessed more electron-rich regions. The narrow energy gap (ΔEgap = 1.87 eV) of BKC (-BCO2) promoted the electron transfer to the substable complex (BKC@PMS*) on SMZ, driving the electron transfer mechanism. In addition, the adsorption energy of BKC(-BCO2)@PMS was lower (-0.75 eV → -5.12 eV), implying a more spontaneous adsorption process. The O-O (PMS) bond length in BKC(-BCO2)@PMS increased significantly (1.412 Š→ 1.481 Å), which led to the easier decomposition of PMS during adsorption and facilitated the generation of 1O2. More importantly, a combination of Gaussian and LC-MS techniques was hypothesized regarding the attack sites and degradation intermediates of the active species in this system. The synergistic T.E.S.T software and toxicity tests predicted low or even no toxicity of the intermediates. Overall, this study proposed a strategy for the preparation of metal-free biochar, aiming to inspire ideas for the treatment of organic-polluted wastewater through advanced oxidation processes (AOPs).

Microplastic dilemma: Assessing the unexpected trade-offs between biodegradable and non-biodegradable forms on plant health, cadmium uptake, and sediment microbial ecology.

Despite extensive substitution of biodegradable plastics (BPs) for conventional plastics (CPs), research on their environmental ecological consequences as microplastics (MPs) is scarce. This study aimed to fill this gap by investigating the impacts of six prototypical MPs (categorized into BMPs and CMPs) on plant growth, cadmium (Cd) translocation, and bacterial communities in contaminated sediments. Results showed both BMPs and CMPs hindered plant development; yet interestingly, BMPs provoked more pronounced physiological and biochemical changes alongside increased oxidative stress due to reactive oxygen species accumulation. Notably, most MP types promoted the absorption of Cd by plant roots potentially via a "dilution effect". BMPs also induced larger shifts in soil microbial metabolic functions compared to CMPs. Ramlibacter was identified as a key biomarker distinguishing BMPs from CMPs, with link to multiple N metabolic pathways and N assimilation. This study offers novel insights into intricate biochemical mechanisms and environmental chemistry behaviors underpinning MP-Cd interactions within the plant-microbe-sediment system, emphasizing BMPs' higher potential ecological risks based on their significant effects on plant health and microbial ecology. This work contributes to enhancing the comprehensive understanding of their ecological implications and potential threats to environmental security.

Oxygen Doping Cooperated with Co-N-Fe Dual-Catalytic Sites: Synergistic Mechanism for Catalytic Water Purification within Nanoconfined Membrane.

Atom-site catalysts, especially for graphitic carbon nitride-based catalysts, represents one of the most promising candidates in catalysis membrane for water decontamination. However, unravelling the intricate relationships between synthesis-structure-properties remains a great challenge. This study addresses the impacts of coordination environment and structure units of metal central sites based on Mantel test, correlation analysis, and evolution of metal central sites. An optimized unconventional oxygen doping cooperated with Co-N-Fe dual-sites (OCN Co/Fe) exhibits synergistic mechanism for efficient peroxymonosulfate activation, which benefits from a significant increase in charge density at the active sites and the regulation in the natural population of orbitals, leading to selective generation of SO4 •-. Building upon these findings, the OCN-Co/Fe/PVDF composite membrane demonstrates a 33 min-1 ciprofloxacin (CIP) rejection efficiency and maintains over 96% CIP removal efficiency (over 24 h) with an average permeance of 130.95 L m-2 h-1. This work offers a fundamental guide for elucidating the definitive origin of catalytic performance in advance oxidation process to facilitate the rational design of separation catalysis membrane with improved performance and enhanced stability.

A non-canonical visual cortical-entorhinal pathway contributes to spatial navigation.

Visual information is important for accurate spatial coding and memory-guided navigation. As a crucial area for spatial cognition, the medial entorhinal cortex (MEC) harbors diverse spatially tuned cells and functions as the major gateway relaying sensory inputs to the hippocampus containing place cells. However, how visual information enters the MEC has not been fully understood. Here, we identify a pathway originating in the secondary visual cortex (V2) and directly targeting MEC layer 5a (L5a). L5a neurons served as a network hub for visual processing in the MEC by routing visual inputs from multiple V2 areas to other local neurons and hippocampal CA1. Interrupting this pathway severely impaired visual stimulus-evoked neural activity in the MEC and performance of mice in navigation tasks. These observations reveal a visual cortical-entorhinal pathway highlighting the role of MEC L5a in sensory information transmission, a function typically attributed to MEC superficial layers before.

The Surface Confinement of FeO Assists in the Generation of Singlet Oxygen and High-Valent Metal-Oxo Species for Enhanced Fenton-Like Catalysis.

Transition metal compounds (TMCs) have long been potential candidate catalysts in persulfate-based advanced oxidation process (PS-AOPs) due to their Fenton-like catalyze ability for radical generation. However, the mechanism involved in TMCs-catalyzed nonradical PS-AOPs remains obscure. Herein, the growth of FeO on the Fe3O4/carbon precursor is regulated by restricted pyrolysis of MIL-88A template to activate peroxymonosulfate (PMS) for tetracycline (TC) removal. The higher FeO incorporation conferred a 2.6 times higher degradation performance than that catalyzed by Fe3O4 and also a higher interference resistance to anions or natural organic matter. Unexpectedly, the quenching experiment, probe method, and electron paramagnetic resonance quantitatively revealed that the FeO reassigned high nonradical species (1O2 and FeIV═O) generation to replace original radical system created by Fe3O4. Density functional theory calculation interpreted that PMS molecular on strongly-adsorbed (200) and (220) facets of FeO enjoyed unique polarized electronic reception for surface confinement effect, thus the retained peroxide bond energetically supported the production of 1O2 and FeIV═O. This work promotes the mechanism understanding of TMCs-induced surface-catalyzed persulfate activation and enables them better perform catalytic properties in wastewater treatment.

Doped Cu0 and sulfidation induced transition from R-O• to •OH in peracetic acid activation by sulfidated nano zero-valent iron-copper.

Peracetic acid (PAA) has emerged as a new effective oxidant for various contaminants degradation through advanced oxidation process (AOP). In this study, sulfidated nano zero-valent iron-copper (S-nZVIC) with low Cu doping and sulfidation was synthesized for PAA activation, resulting in more efficient degradation of sulfamethoxazole (SMX, 20 µM) and other contaminants using a low dose of catalyst (0.05 g/L) and oxidant (100 µM). The characterization results suggested that S-nZVIC presented a more uniform size and distribution with fewer metal oxides, as the agglomeration and oxidation were inhibited. More significantly, doped Cu0 and sulfidation significantly enhanced the generation and contribution of •OH but decreased that of R-O• in S-nZVIC/PAA/SMX system compared with that of nZVIC and S-nZVI, accounting for the relatively high degradation efficiency of 97.7% in S-nZVIC/PAA/SMX system compared with 85.7% and 78.9% in nZVIC/PAA/SMX and S-nZVI/PAA/SMX system, respectively. The mechanisms underlying these changes were that (i) doped Cu° could promote the regeneration of Fe(Ⅱ) for strengthened PAA activation through mediating Fe(Ⅱ)/Fe(Ⅲ) cycle by Cu(Ⅰ)/Cu(Ⅱ) cycle; (ii) S species might consume part of R-O•, resulting in a decreased contribution of R-O• in SMX degradation; (iii) sulfidation increased the electrical conductivity, thus facilitating the electron transfer from S-nZVIC to PAA. Consequently, the dominant reactive oxygen species transited from R-O• to •OH to degrade SMX more efficiently. The degradation pathways, intermediate products and toxicity were further analyzed through density functional theory (DFT) calculations, liquid chromatography-mass spectrometry (LC-MS) and T.E.S.T software analysis, which proved the environmental friendliness of this process. In addition, S-nZVIC exhibited high stability, recyclability and degradation efficiency over a wide pH range (3.0∼9.0). This work provides a new insight into the rational design and modification of nano zero-valent metals for efficient wastewater treatment through adjusting the dominant reactive oxygen species (ROS) into the more active free radicals.

Simultaneous elimination of antibiotic-resistant bacteria and antibiotic resistance genes by different Fe-N co-doped biochars activating peroxymonosulfate: The key role of pyridine-N and Fe-N sites.

The coexistence of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in the environment poses a potential threat to public health. In our study, we have developed a novel advanced oxidation process for simultaneously removing ARGs and ARB by two types of iron and nitrogen-doped biochar derived from rice straw (FeN-RBC) and sludge (FeN-SBC). All viable ARB (approximately 108 CFU mL-1) was inactivated in the FeN-RBC/ peroxymonosulfate (PMS) system within 40 min and did not regrow after 48 h even in real water samples. Flow cytometry identified 96.7 % of dead cells in the FeN-RBC/PMS system, which verified the complete inactivation of ARB. Thorough disinfection of ARB was associated with the disruption of cell membranes and intracellular enzymes related to the antioxidant system. Whereas live bacteria (approximately 200 CFU mL-1) remained after FeN-SBC/PMS treatment. Intracellular and extracellular ARGs (tetA and tetB) were efficiently degraded in the FeN-RBC/PMS system. The production of active species, primarily •OH, SO4•- and Fe (IV), as well as electron transfer, were essential to the effective disinfection of FeN-RBC/PMS. In comparison with FeN-SBC, the better catalytic performance of FeN-RBC was mainly ascribed to its higher amount of pyridine-N and Fe0, and more reactive active sites (such as CO group and Fe-N sites). Density functional theory calculations indicated the greater adsorption energy and Bader charge, more stable Fe-O bond, more easily broken OO bond in FeN-RBC/PMS, which demonstrated the stronger electron transfer capacity between FeN-RBC and PMS. To encapsulate, our study provided an efficient and dependable method for the simultaneous elimination of ARGs and ARB in water.

Microplastics/nanoplastics in porous media: Key factors controlling their transport and retention behaviors.

Till now, microplastics/nano-plastics(M/NPs) have received a lot of attention as emerging contaminant. As a typical but complex porous medium, soil is not only a large reservoir of M/NPs but also a gateway for M/NPs to enter groundwater. Therefore, the review of the factors controlling the transport behavior of M/NPs in porous media can provide important guidance for the risk assessment of M/NPs in soil and groundwater. In this study, the key factors controlling the transport behavior of M/NPs in porous media are systematically divided into three groups: (1) nature of M/NPs affecting M/NPs transport in porous media, (2) nature of flow affecting M/NPs transport in porous media, (3) nature of porous media affecting M/NPs transport. In each group, the specific control factors for M/NPs transport in porous media are discussed in detail. In addition to the above factors, some substances (colloids or pollutants) present in natural porous media (such as soil or sediments) will co-transport with M/NPs and affect its mobility. According to the different properties of co-transported substances, the mechanism of promoting or inhibiting the migration behavior of M/NPs in porous media was discussed. Finally, the limitations and future research directions of M/NPs transport in porous media are pointed out. This review can provide a useful reference for predicting the transport of M/NPs in natural porous media.

DFT Predirected Molecular Engineering Design of Donor-Acceptor Structured g-C3N4 for Efficient Photocatalytic Tetracycline Abatement.

The photocatalytic environmental decontamination ability of carbon nitride (g-C3N4, CN) typically suffers from their inherent structural defects, causing rapid recombination of photogenerated carriers. Conjugating CN with tailored donor-acceptor (D-A) units to counteract this problem through electronic restructuring becomes a feasible strategy, where confirmation by density functional theory (DFT) calculations becomes indispensable. Herein, DFT is employed to predirect the copolymerization modification of CN by benzene derivatives, screening benzaldehyde as the optimal electron-donating candidate for the construction of reoriented intramolecular charge transfer path. Experimental characterization and testing corroborate the formation of a narrowed bandgap as well as high photoinduced carrier separation. Consequently, the optimal BzCN-2 exhibited superior photocatalytic capacity in application for tetracycline hydrochloride degradation, with 3.73 times higher than that of CN. Besides, the BzCN-2-based photocatalytic system is determined to have a toxicity-mitigating effect on TC removal via T.E.S.T and prefers the removal of dissociable TC2- species under partial alkalinity. This work provides insight into DFT guidance for the design of D-A conjugated polymer and its application scenarios in photocatalytic decontamination.

FeSe2 and Its Composites for Pollutants Removal: Synthesis, Mechanisms, and Application Potential.

In recent years, the research of FeSe2 and its composites in environmental remediation has been gradually carried out. And the FeSe2 materials show great catalytic performance in photocatalysis, electrocatalysis, and Fenton-like reactions for pollutants removal. Therefore, the studies and applications of FeSe2 materials are reviewed in this work, including the common synthesis methods, the role of Fe and Se species as well as the catalyst structure, and the potential for practical environmental applications. Hereinto, it is worth noting in particular that the lower-valent Se (Se2-), unsaturated Se (Se-), and Se vacancies (VSe) can play different roles in promoting pollutants removal. In addition, the FeSe2 material also demonstrates high stability, reusability, and adaptability over a wider pH range as well as universality to different pollutants. In view of the overall great properties and performance of FeSe2 materials compared with other typical Fe-based materials, it deserves and needs further research. And finally, this paper presents some challenges and perspectives in future development, looking forward to providing helpful guidance for the subsequent research of FeSe2 and its composites for environmental application.

In sight the behavior of natural Bletilla striata polysaccharide hydrocolloids by molecular dynamics method.

Plant polysaccharides, distinguished by diverse glycosidic bonds and various cyclic sugar units, constitute a subclass of primary metabolites ubiquitously found in nature. Contrary to common understanding, plant polysaccharides typically form hydrocolloids upon dissolution in water, even though both excessively high and low temperatures impede this process. Bletilla striata polysaccharides (BSP), chosen for this kinetic study due to their regular repeating units, help elucidate the relationship between polysaccharide gelation and temperature. It is suggested that elevated temperatures enhance the mobility of BSP molecular chains, resulting in a notable acceleration of hydrogen bond breakage between BSP and water molecules and consequently, compromising the conformational stability of BSPs to some extent. This study unveils the unique relationship between polysaccharide dissolution processes and temperature from a kinetics perspective. Consequently, the conclusion provides a dynamical basis for comprehending the extraction and preparation of natural plant polysaccharide hydrocolloids, pharmaceuticals and related fields.

Protocol to study microcircuits in the medial entorhinal cortex in mice using multiple patch-clamp recordings and morphological reconstruction.

Multiple patch-clamp recordings and morphological reconstruction are powerful approaches for neuronal microcircuitry dissection and cell type classification but are challenging due to the sophisticated expertise needed. Here, we present a protocol for applying these techniques to neurons in the medial entorhinal cortex (MEC) of mice. We detail steps to prepare brain slices containing MEC and perform simultaneous multiple whole-cell recordings, followed by procedures of histological staining and neuronal reconstruction. We then describe how we analyze morphological and electrophysiological features. For complete details on the use and execution of this protocol, please refer to Shi et al.1.

High pyroptosis activity in pancreatic adenocarcinoma: poor prognosis and oxaliplatin resistance.

BACKGROUND: Pyroptosis, as a type of inflammatory programmed cell death, has been studied in inflammatory diseases and numerous cancers but its role in pancreatic ductal adenocarcinoma (PDAC) remains further exploration. METHODS: A TCGA-PDAC cohort was enrolled for bioinformatics analysis to investigate the effect of pyroptosis on the prognosis and drug sensitivity of patients. PA-TU-8988T and CFPAC-1 cells were selected for investigating the role of GSDMC in PDAC. RESULTS: A distinct classification pattern of PDAC mediated by 21 pyroptosis-related genes (PRGs) was identified. It was suggested that higher pyroptosis activity was associated with poor prognosis of patients and higher tumor proliferation rates. We further established a prognostic model based on three PRGs (GSDMC, CASP4 and NLRP1) and the TCGA-PDAC cohort was classified into low and high-risk subgroups. It is noteworthy that the high-risk group showed significantly higher tumor proliferation rates and was proved to be highly correlated with oxaliplatin resistance. Further experiments suggested that overexpression of GSDMC promoted the proliferation and oxaliplatin resistance of PA-TU-8988T cells in vitro and vivo, while downregulation of GSDMC showed opposite effects in CFPAC-1 cells. Finally, we found that the activation of pentose phosphate pathway (PPP) was the mechanism by which GSDMC overexpression promoted the proliferation and oxaliplatin resistance of pancreatic cancer cells. CONCLUSIONS: In this study, we found that higher pyroptosis activity is associated with worse prognosis and oxaliplatin resistance of PDAC patients. In addition, as a core effector of pyroptosis, GSDMC promoted proliferation and oxaliplatin resistance of pancreatic cancer cells, which will provide new therapeutic target for PDAC patients.

Laminar and dorsoventral organization of layer 1 interneuronal microcircuitry in superficial layers of the medial entorhinal cortex.

Layer 1 (L1) interneurons (INs) participate in various brain functions by gating information flow in the neocortex, but their role in the medial entorhinal cortex (MEC) is still unknown, largely due to scant knowledge of MEC L1 microcircuitry. Using simultaneous triple-octuple whole-cell recordings and morphological reconstructions, we comprehensively depict L1IN networks in the MEC. We identify three morphologically distinct types of L1INs with characteristic electrophysiological properties. We dissect intra- and inter-laminar cell-type-specific microcircuits of L1INs, showing connectivity patterns different from those in the neocortex. Remarkably, motif analysis reveals transitive and clustered features of L1 networks, as well as over-represented trans-laminar motifs. Finally, we demonstrate the dorsoventral gradient of L1IN microcircuits, with dorsal L1 neurogliaform cells receiving fewer intra-laminar inputs but exerting more inhibition on L2 principal neurons. These results thus present a more comprehensive picture of L1IN microcircuitry, which is indispensable for deciphering the function of L1INs in the MEC.

Modified nano zero-valent iron reduce toxicity of polystyrene microplastics to ryegrass (Lolium Perenne L.).

Microplastics pollution in environments has become a major concern and it has been proven to have adverse impacts on plants, so there is an urgent to find approaches to alleviate the detrimental effects of microplastics. In our study, we investigated the influence of polystyrene microplastics (PSMPs) on the growth, photosynthesis, and oxidative defense system changes of ryegrass, as well as the behavior of MPs at roots. Then three types of nanomaterials were applied to alleviate the adverse impact of PSMPs on ryegrass, which were nano zero-valent iron (nZVI), carboxymethylcellulose-modified-nZVI (C-nZVI) and sulfidated nZVI (S-nZVI), respectively. Our results suggested that PSMPs had significant toxicity to ryegrass, leading to decrease of shoot weight, shoot length and root length. Three nanomaterials regained the weight of ryegrass to a varying extent and made more PSMPs aggregate near roots. In addition, C-nZVI and S-nZVI facilitated the entrance of PSMPs into the root and promoted the chlorophyll a and chlorophyll b contents in leaves. Analysis of antioxidant enzymes and malondialdehyde content indicated that ryegrass coped well with the internalization of PSMPs, and all three types of nZVI could alleviate PSMPs-stress in ryegrass. This study elaborates the toxicity of MPs on plants and provides a novel insight into the fixing of MPs by plants and nanomaterials in environments, which needs to be further explored in future research.

Celiac ganglia neurolysis suppresses high blood pressure in rats.

The efficacy of renal denervation in the treatment of resistant hypertension has been controversial, and new strategies for its therapy are urgently needed. We performed the celiac ganglia neurolysis (CGN) or sham surgery on both spontaneously hypertensive rat (SHR) and Dahl salt-sensitive rat models of hypertension. Following CGN surgery in both strains, systolic blood pressure, diastolic blood pressure and mean arterial pressure were all lower than the levels in the respective sham surgery rats, which were maintained until the end of the study, 18 weeks postoperatively in SHRs and 12 weeks postoperatively in Dahl rats. CGN therapy destroyed ganglion cell structure and significantly inhibited celiac ganglia nerve viability. Four and twelve weeks after CGN, the plasma renin, angiotensin II and aldosterone levels were markedly attenuated, and the nitric oxide content was significantly increased in the CGN group compared with the respective sham surgery rats. However, CGN did not result in statistical difference in malondialdehyde levels compared with sham surgery in both strains. The CGN has efficacy in reducing high blood pressure and may be an alternative for resistant hypertension. Minimally invasive endoscopic ultrasound-guided celiac ganglia neurolysis (EUS-CGN) and percutaneous CGN are safe and convenient treatment approaches. Moreover, for hypertensive patients who need surgery due to abdominal disease or pain relief from pancreatic cancer, intraoperative CGN or EUS-CGN will be a good choice for hypertension therapy. The graphical abstract of antihypertensive effect of CGN.

Risk factors of delayed gastric emptying in patients after pancreaticoduodenectomy: a comprehensive systematic review and meta-analysis.

BACKGROUND: Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PPPD). However, its risk factors are still unclear. This meta-analysis aimed to identify the potential risk factors of DGE among patients undergoing PD or PPPD. MATERIALS AND METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Google Scholar, and ClinicalTrial.gov for studies that examined the clinical risk factors of DGE after PD or PPPD from inception through 31 July 2022. We pooled odds ratios (ORs) with 95% CIs using random-effects or fixed-effects models. We also performed heterogeneity, sensitivity, and publication bias analyses. RESULTS: The study included a total of 31 research studies, which involved 9205 patients. The pooled analysis indicated that out of 16 nonsurgical-related risk factors, three risk factors were found to be associated with an increased incidence of DGE. These risk factors were older age (OR 1.37, P =0.005), preoperative biliary drainage (OR 1.34, P =0.006), and soft pancreas texture (OR 1.23, P =0.04). On the other hand, patients with dilated pancreatic duct (OR 0.59, P =0.005) had a decreased risk of DGE. Among 12 operation-related risk factors, more blood loss (OR 1.33, P =0.01), postoperative pancreatic fistula (POPF) (OR 2.09, P <0.001), intra-abdominal collection (OR 3.58, P =0.001), and intra-abdominal abscess (OR 3.06, P <0.0001) were more likely to cause DGE. However, our data also revealed 20 factors did not support stimulative factors influencing DGE. CONCLUSION: Age, preoperative biliary drainage, pancreas texture, pancreatic duct size, blood loss, POPF, intra-abdominal collection, and intra-abdominal abscess are significantly associated with DGE. This meta-analysis may have utility in guiding clinical practice for improvements in screening patients with a high risk of DGE and selecting appropriate treatment measures.

Metformin inhibits neutrophil extracellular traps-promoted pancreatic carcinogenesis in obese mice.

Obesity has been linked to a higher risk of pancreatic cancer. However, the mechanism by which obesity promote pancreatic carcinogenesis is still unclear. We investigated the effect of obesity on pancreatic carcinogenesis in Pdx1-Cre; LSL-KrasG12D+/- (KC) mice. Metformin was administrated to rescue the effects of obesity and NETs. The pro-tumorigenic effects of neutrophil extracellular traps (NETs) were further evaluated in vivo and vitro. We found that obesity significantly promoted the progression of murine pancreatic ductal intraepithelial neoplasia (mPanIN). The proliferation rate and epithelial-mesenchymal transition (EMT) of mPanIN ductal cells were increased in obese mice. More visceral adipocytes, PD-L1+ neutrophil infiltration and NETs formation were found in the pancreas of obese mice and visceral adipocytes could recruit neutrophils and promote NETs formation. The latter could induce an inflammatory response in ductal cells via TLR4-dependent pathways both in vivo and vitro, as demonstrated by upregulation of IL-1ß. Metformin and DNase I significantly reversed the pro-tumorigenic effects of obesity and NETs in vivo and in vitro. Our study provides causal evidence for the contribution of obesity in promoting pancreatic carcinogenesis in genetic model and reveals the mechanism by NETs to regulate mPanIN progression.