Effect of the Step-Jump Approach in Infected Pancreatic Necrosis: A Propensity Score-Matched Study.

Purpose: The effects of the step-jump approach on the survival and prognosis of infected pancreatic necrosis (IPN) patients have not yet been determined. Patients and Methods: Between November 2018 and June 2023, 188 patients were included in this study. There were 144 patients in the step-up group (the SU group) and 44 in the step-jump group (the SJ group). In the SU group, patients successfully treated with percutaneous catheter drainage (PCD) alone were classified into the SU-1 group (n=101), while those requiring additional surgery after PCD were categorized into the SU-2 group (n=43). In the SJ group, patients who underwent minimally invasive necrosectomy (MIN) without PCD were assigned to the SJ-1 group (n=34), whereas those who initially underwent PCD followed by immediate open surgery were placed in the SJ-2 group (n=10). Propensity score matching (PSM) was used to mitigate bias. Results: After PSM, a total of 34 pairs were successfully matched. A comparison of the SU group with the SJ-1 group (upfront MIN without PCD) revealed similar mortality rates (P=0.239); however, the incidences of multiple drug-resistant organisms (MDROs) (P=0.029) and surgical complications (P<0.001) were significantly lower in the SJ-1 group. After comparing the SU-2 and SJ-2 groups (patients who underwent direct open necrosectomy without MIN after PCD failure), the incidences of surgical complications and MDRO in the SJ-2 group were significantly lower (P<0.05). Conclusion: Compared with the step-up approach, the step-jump approach is safer and more effective and can significantly reduce the incidence of MDRO and surgical complications.

Antibiotics Trigger Host Innate Immune Response via Microbiota-Brain Communication in C. elegans.

Besides their direct bactericidal effect, antibiotics have also been suggested to stimulate the host immune response to defend against pathogens. However, it remains unclear whether any antibiotics may stimulate the host immune response by affecting bacterial activity. In this study, reasoning that genetic mutations inhibit bacterial activities and, thereby, may mimic the effects of antibiotics, we performed genome-wide screening and identified 77 E. coli genes whose inactivation induces C. elegans cyp-14A4, representing an innate immune and detoxification response. Further analyses reveal that this host immune response can clearly be induced through either inactivating the E. coli respiratory chain via the bacterial cyoB mutation or using the antibiotic Q203, which is able to enhance host survival when encountering the pathogen Pseudomonas aeruginosa. Mechanistically, the innate immune response triggered by both the cyoB mutation and Q203 is found to depend on the host brain response, as evidenced by their reliance on the host neural gene unc-13, which is required for neurotransmitter release in head neurons. Therefore, our findings elucidate the critical involvement of the microbiota-brain axis in modulating the host immune response, providing mechanistic insights into the role of antibiotics in triggering the host immune response and, thus, facilitating host defense against pathogens.

m-Aminophenylacetylene induces maternal care in a predatory spider.

Maternal care is critically important for the survival of offspring in various animals. Spiders in the family Lycosidae are known for their hunting ability and maternal care behaviors. Predation on newly hatched spiderlings (pulli) by mother spiders decreases when they come into contact, and they carry the pulli on their dorsal surface. However, the factors inducing maternal care in lycosid spiders have not been elucidated. In this study, we investigated maternal care in Pardosa pseudoannulata (Araneae, Lycosidae) females. We proposed that the physical interaction between pulli and mother spiders induces maternal care via m-aminophenylacetylene (m-A), a novel regulator of maternal care. The presence of pulli on the dorsal abdomen of non-mother spiders suppressed pulli predation and increased the pulli-carrying rate, and the absence of pulli on the mother spiders increased pulli predation and decreased the pulli-carrying rate. The compound m-A was abundant in mother spiders, and it could be induced in non-mother spiders when they carried pulli. The topical application of m-A to non-mother spiders and m-A injection decreased pulli predation and increased the pulli-carrying rate, respectively; these findings indicate that m-A in both internal tissues and the integument is required for the induction of maternal care behavior, and the interaction between pulli and females induces the production of m-A. In-depth study of the regulatory mechanism of maternal care will enhance our understanding of spider biology and behavior.

Caprin-1 influences autophagy-induced tumor growth and immune modulation in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by rapid progression and poor prognosis. Understanding the genetic mechanisms that affect cancer properties and reprogram tumor immune microenvironment will develop new strategies to maximize the benefits for cancer therapies. METHODS: Gene signatures and biological processes associated with advanced cancer and unfavorable outcome were profiled using bulk RNA sequencing and spatial transcriptome sequencing, Caprin-1 was identified as an oncogenesis to expedite pancreatic cancer growth by activating autophagy. The mechanism of Caprin-1 inducing autophagy activation was further explored in vitro and in vivo. In addition, higher level of Caprin-1 was found to manipulate immune responses and inflammatory-related pathways. The immune profiles associated with increased levels of Caprin-1 were identified in human PDAC samples. The roles of CD4+T cells, CD8+T cells and tumor associated macrophages (TAMs) on clinical outcomes prediction were investigated. RESULTS: Caprin-1 was significantly upregulated in advanced PDAC and correlated with poor prognosis. Caprin-1 interacted with both ULK1 and STK38, and manipulated ULK1 phosphorylation which activated autophagy and exerted pro-tumorigenic phenotypes. Additionally, the infiltrated CD4+T cells and tumor associated macrophages (TAMs) were increased in Caprin-1High tissues. The extensive CD4+T cells determined poor clinical outcome in Caprin-1high patients, arguing that highly expressed Caprin-1 may assist cancer cells to escape from immune surveillance. CONCLUSIONS: Our findings establish causal links between the upregulated expression of Caprin-1 and autophagy activation, which may manipulate immune responses in PDAC development. Our study provides insights into considering Caprin-1 as potential therapeutic target for PDAC treatment.

Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis.

Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. Moreover, Bacteroides uniformis or taurine inhibits the activation of NF-κB and IL-17 signaling pathways in neutrophils which harness NETs and alleviate pancreatic injury. Our findings establish roles of endogenous Bacteroides uniformis-derived metabolic and inflammatory products on suppressing NETs release, which provides potential insights of ameliorating HTGP through gut microbiota modulation.

circEIF3I facilitates the recruitment of SMAD3 to early endosomes to promote TGF-ß signalling pathway-mediated activation of MMPs in pancreatic cancer.

BACKGROUND: Among digestive tract tumours, pancreatic ductal adenocarcinoma (PDAC) shows the highest mortality trend. Moreover, although PDAC metastasis remains a leading cause of cancer-related deaths, the biological mechanism is poorly understood. Recent evidence demonstrates that circular RNAs (circRNAs) play important roles in PDAC progression. METHODS: Differentially expressed circRNAs in normal and PDAC tissues were screened via bioinformatics analysis. Sanger sequencing, RNase R and actinomycin D assays were performed to confirm the loop structure of circEIF3I. In vitro and in vivo functional experiments were conducted to assess the role of circEIF3I in PDAC. MS2-tagged RNA affinity purification, mass spectrometry, RNA immunoprecipitation, RNA pull-down assay, fluorescence in situ hybridization, immunofluorescence and RNA-protein interaction simulation and analysis were performed to identify circEIF3I-interacting proteins. The effects of circEIF3I on the interactions of SMAD3 with TGFßRI or AP2A1 were measured through co-immunoprecipitation and western blotting. RESULTS: A microarray data analysis showed that circEIF3I was highly expressed in PDAC cells and correlated with TNM stage and poor prognosis. Functional experiments in vitro and in vivo revealed that circEIF3I accelerated PDAC cells migration, invasion and metastasis by increasing MMPs expression and activity. Mechanistic research indicated that circEIF3I binds to the MH2 domain of SMAD3 and increases SMAD3 phosphorylation by strengthening the interactions between SMAD3 and TGFßRI on early endosomes. Moreover, AP2A1 binds with circEIF3I directly and promotes circEIF3I-bound SMAD3 recruitment to TGFßRI on early endosomes. Finally, we found that circEif3i exerts biological functions in mice similar to those of circEIF3I in humans PDAC. CONCLUSIONS: Our study reveals that circEIF3I promotes pancreatic cancer progression. circEIF3I is a molecular scaffold that interacts with SMAD3 and AP2A1 to form a ternary complex, that facilitates the recruitment of SMAD3 to early endosomes and then activates the TGF-ß signalling pathway. Hence, circEIF3I is a potential prognostic biomarker and therapeutic target in PDAC.

Declined Live Birth Rate from in vitro Fertilization Fresh Cycles Performed During Chinese New Year Holiday Season.

Purpose: This study aims to investigate the impact of the Chinese New Year (CNY) holiday season on the outcomes of In Vitro Fertilization (IVF) fresh embryo transfer cycles. Participants and Methods: This retrospective study analyzed 4688 patients who received their first IVF fresh cycle attempt between January 2017 and October 2021. Of these, 4449 women underwent IVF during non-holiday seasons, while 239 women were treated during the CNY holiday season. The study included women who underwent IVF treatment during the specified time frame. The primary outcome was the live birth rate (LBR). Results: The study found that the LBR of IVF performed during the CNY holiday season was 32.22%, which is significantly lower than that of the non-holiday season (43.38%, p<0.001). Multivariate logistic regression analysis showed that the CNY holiday season (OR=0.62, 95% CI 0.47-0.82, p=0.001) was an independent factor associated with the live birth rate. Propensity score matching (PSM) data analysis showed that the LBR in the CNY holiday season group was 31.78% compared to 42.64% in the non-holiday season group (p=0.005). Inverse probability of treatment weighting (IPTW) data also indicated that the CNY holiday season had a lower LBR than the non-holiday season (OR=0.64, 95% CI 0.47-0.87, p=0.005). Conclusion: IVF performed during the CNY holiday season results in a lower live birth rate, potentially indicating that certain lifestyle adjustments during this period, such as unhealthy dietary, tobacco and alcohol usage, sleep disruption, and emotional stress experienced could have some influence on the outcomes.

Live Birth Outcomes for PCOS Patients Under the Follicular-Phase Long-Acting GnRH Agonist Protocol or Antagonist Protocol - A Retrospective Chinese Cohort.

Objective: For patients with polycystic ovary syndrome (PCOS) to undergo in vitro fertilization (IVF) and embryo transfer (ET), there has been no consensus regarding which protocol is the most optimal for live birth rate in fresh cycles. We sought to evaluate depot gonadotropin-releasing hormone (GnRH) agonist protocol versus GnRH antagonist protocol in IVF outcomes for PCOS patients in a single fertility center. Methods: In this retrospective cohort, PCOS patients who visited the Second Hospital of Hebei Medical University reproductive center between February 2012 and December 2019 were screened, and 533 PCOS infertility patients were included undergoing their first IVF cycle, with 470 in the depot GnRH agonist group and 63 in the GnRH antagonist group. The primary of this study outcome was the fresh live birth rate (LBR). Results: PCOS women in the depot GnRH agonist group had a higher LBR (49.79%) than those in the GnRH antagonist group (34.92%, p = 0.027). The multivariable logistic regression also confirmed that women in the depot GnRH agonist group had a higher LBR than those in the GnRH antagonist group (OR = 1.83, 95% CI 1.05~3.18, p = 0.032). After propensity score matching (PSM), the LBR in the depot GnRH agonist group was higher (50.32%) than that of the GnRH antagonist group (35.48%), p = 0.033. The ovarian hyperstimulation syndrome (OHSS) rates were similar between the two groups, with 35 in the depot GnRH group and 6 in the GnRH antagonist group (p = 0.561). Conclusions: For PCOS patients in fresh embryo transfer cycles, the depot GnRH agonist protocol may lead to a higher LBR than the antagonist protocol with satisfied lower OHSS rates.

Pore-Scale Study on Shale Oil-CO2-Water Miscibility, Competitive Adsorption, and Multiphase Flow Behaviors.

Due to the fracturing fluid imbibition and primary water, oil-water two-phase fluids generally exist in shale nanoporous media. The effects of water phase on shale oil recovery and geological carbon sequestration via CO2 huff-n-puff is non-negligible. Meanwhile, oil-CO2 miscibility after CO2 huff-n-puff also has an important effect on oil-water two-phase flow behaviors. In this work, by considering the oil-CO2 competitive adsorption behaviors and the effects of oil-CO2 miscibility on water wettability, an improved multicomponent and multiphase lattice Boltzmann method is proposed to study the effects of water phase on CO2 huff-n-puff. Additionally, the effects of oil-CO2 miscibility on oil-water flow behaviors and relative permeability are also discussed. The results show that due to Jamin's effect of water droplets in oil-wetting pores and the capillary resistance of bridge-like water phase in water-wetting pores, CO2 can hardly diffuse into the oil phase, causing a large amount of remaining oil. As water saturation increases, Jamin's effect and the capillary resistance become more pronounced, and the CO2 storage mass gradually decreases. Then, based on the results from molecular dynamics simulations, the influences of oil-CO2 miscibility on oil-water relative permeability in calcite nanoporous media are studied, and as the oil mass percentage in the oil-CO2 miscible system decreases, the oil/water relative permeability decreases/increases. The improved lattice Boltzmann model can be readily extended to quantitatively calculate geological CO2 storage mass considering water saturation and calculate the accurate oil-water relative permeability based on the real 3D digital core.

Gut microbiota affects pancreatic fibrotic progression through immune modulation in chronic pancreatitis.

Chronic pancreatitis (CP) is characterized by chronic progressive pancreatic inflammation, which leads to the permanent damage of exocrine and endocrine cells. CP causes irreversible morphological and functional changes, and the clinical manifestations includes abdomen pain, steatorrhea and diabetes. CP induces changes in the composition of gut microbiota that could be used as potential biomarkers for pancreatic fibrosis evaluation. Gut microbiota has emerged as key regulator of immunomodulation and gut microbiota-induced immune activation has not been explored in CP. In current study, we profiled gut microbial signatures in mouse CP model, and found that higher proportion of Streptomyces, Turicibacter, Methylobacterium, Enterococcus and Candidatus_Paenicardiniummore were positively associated with the occurrence of pancreatic fibrosis. We then identified increased CD3+T cells and macrophage infiltration in mouse and human CP tissues by transcriptome sequencing data from GEO database. Subsequently, we demonstrated that fecal microbiota transplantation (FMT) from CP mouse (FMT-CP) exacerbated pancreatic fibrosis by increasing CD4+T cells and macrophage infiltration compared to fecal samples obtained from healthy mouse donor (FMT-HC). Our study describes the link between gut microbiota dysbiosis and immune activation in pancreatic fibrotic progression, and highlights the potential therapeutic roles of FMT and CP treatment.

Tumor Cell Derived Lnc-FSD2-31:1 Contributes to Cancer-Associated Fibroblasts Activation in Pancreatic Ductal Adenocarcinoma Progression through Extracellular Vesicles Cargo MiR-4736.

Pancreatic ductal adenocarcinoma (PDAC) presents with high mortality and short overall survival. Cancer-associated fibroblasts (CAFs) act as refuge for cancer cells in PDAC. Mechanisms of intracelluar communication between CAFs and cancer cells need to be explored. Long noncoding RNAs (lncRNAs) are involved in the modulation of oncogenesis and tumor progression of PDAC; however, specific lncRNAs and their mechanism of action have not been clarified clearly in tumoral microenvironment. This work aims to identify novel lncRNAs involved in cellular interaction between cancer cells and CAFs in PDAC. To this end, differentially expressed lncRNAs between long-term and short-term survival PDAC patients are screened. Lnc-FSD2-31:1 is found to be significantly increased in long-term survival patients. This work then discovers that tumor-derived lnc-FSD2-31:1 restrains CAFs activation via miR-4736 transported by extracellular vesicles (EVs) in vitro and in vivo. Mechanistically, EVs-derived miR-4736 suppresses autophagy and contributes to CAFs activation by targeting ATG7. Furthermore, blocking miR-4736 suppresses tumor growth in genetically engineered KPC (LSL-KrasG12D/+, LSL-Trp53R172H/+, and Pdx-1-Cre) mouse model of PDAC. This study demonstrates that intratumoral lnc-FSD2-31:1 modulates autophagy in CAFs resulting in their activation through EVs-derived miR-4736. Targeting miR-4736 may be a potential biomarker and therapeutic target for PDAC.

IGF2BP1-mediated N6-methyladenosine modification promotes intrahepatic cholangiocarcinoma progression.

N6-methyladenosine (m6A) RNA methylation and its associated RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) are involved in tumor initiation and progression. Here, we explored the biological function and clinical significance of IGF2BP1 in intrahepatic cholangiocarcinoma (iCCA). We found that IGF2BP1 expression was upregulated by H3K27 acetylation enrichment of its promoter, which positively correlated with poor clinicopathological characteristics and survival. Gain- and loss-of-function experiments showed that IGF2BP1 overexpression (knockdown) enhanced (attenuated) iCCA growth and metastasis in vitro and in vivo. Mechanistically, IGF2BP1 not only regulated the c-Myc/p16 axis to promote iCCA growth and inhibit senescence, but also activated the ZIC2/PAK4/AKT/MMP2 axis to induce tumor metastasis. More importantly, BTYNB, a recently identified IGF2BP1 inhibitor, exerted promising anti-tumor efficacy in a patient-derived xenograft (PDX) model, and IGF2BP1 conditional knockout (cKO) reduced the tumor burden. These results demonstrate the crucial role of IGF2BP1 in iCCA progression via m6A-dependent modification, highlighting IGF2BP1 as a potential therapeutic target in iCCA.

Gut microbiota-derived nicotinamide mononucleotide alleviates acute pancreatitis by activating pancreatic SIRT3 signalling.

BACKGROUND AND PURPOSE: Gut microbiota dysbiosis induced by acute pancreatitis (AP) exacerbates pancreatic injury and systemic inflammatory responses. The alleviation of gut microbiota dysbiosis through faecal microbiota transplantation (FMT) is considered a potential strategy to reduce tissue damage and inflammation in many clinical disorders. Here, we aim to investigate the effect of gut microbiota and microbiota-derived metabolites on AP and further clarify the mechanisms associated with pancreatic damage and inflammation. EXPERIMENTAL APPROACH: AP rat and mouse models were established by administration of caerulein or sodium taurocholate in vivo. Pancreatic acinar cells were exposed to caerulein and lipopolysaccharide in vitro to simulate AP. KEY RESULTS: Normobiotic FMT alleviated AP-induced gut microbiota dysbiosis and ameliorated the severity of AP, including mitochondrial dysfunction, oxidative damage and inflammation. Normobiotic FMT induced higher levels of NAD+ (nicotinamide adenine dinucleotide)-associated metabolites, particularly nicotinamide mononucleotide (NMN). NMN administration mitigated AP-mediated mitochondrial dysfunction, oxidative damage and inflammation by increasing pancreatic NAD+ levels. Similarly, overexpression of the NAD+ -dependent mitochondrial deacetylase sirtuin 3 (SIRT3) alleviated the severity of AP. Furthermore, SIRT3 deacetylated peroxiredoxin 5 (PRDX5) and enhanced PRDX5 protein expression, thereby promoting its antioxidant and anti-inflammatory activities in AP. Importantly, normobiotic FMT-mediated NMN metabolism induced SIRT3-PRDX5 pathway activation during AP. CONCLUSION AND IMPLICATIONS: Gut microbiota-derived NMN alleviates the severity of AP by activating the SIRT3-PRDX5 pathway. Normobiotic FMT could be served as a potential strategy for AP treatment.

The Interaction of Microbiome and Pancreas in Acute Pancreatitis.

Acute pancreatitis (AP) is a common acute abdomen disease characterized by the pathological activation of digestive enzymes and the self-digestion of pancreatic acinar cells. Secondary infection and sepsis are independent prognosticators for AP progression and increased mortality. Accumulating anatomical and epidemiological evidence suggests that the dysbiosis of gut microbiota affects the etiology and severity of AP through intestinal barrier disruption, local or systemic inflammatory response, bacterial translocation, and the regulatory role of microbial metabolites in AP patients and animal models. Recent studies discussing the interactions between gut microbiota and the pancreas have opened new scopes for AP, and new therapeutic interventions that target the bacteria community have received substantial attention. This review concentrates on the alterations of gut microbiota and its roles in modulating gut-pancreas axis in AP. The potential therapies of targeting microbes as well as the major challenges of applying those interventions are explored. We expect to understand the roles of microbes in AP diagnosis and treatment.

Fibrinogen-like Protein 1 as a Predictive Marker for the Incidence of Severe Acute Pancreatitis and Infectious Pancreatic Necrosis.

Background and Objectives: Acute pancreatitis (AP) is defined as an acute inflammatory disorder of the pancreas and is a common gastrointestinal disease. Since currently used indicators lack specifics and cannot accurately reflect the phase of disease, better diagnostic approaches need to be explored. Fibrinogen-like protein 1 (FGL-1) is a reactant in acute inflammatory diseases and is increased in the plasma of AP patients. In the current study, we aim to investigate the clinical benefits of FGL-1 in predicting the severity of AP and infected pancreatic necrosis (IPN), which can improve the diagnostic efficiency of AP. Materials and Methods: In this study, 63 patients diagnosed with AP from December 2018 to September 2019 were enrolled. Regarding the severity of AP, patients were separated into severe acute pancreatitis (SAP, n = 12) and No-SAP groups (n = 51). On the basis of infective conditions, patients were divided into IPN (n = 9) and No-IPN (n = 54) groups. The demographic data (sex and age) and blood parameters (WBC, HCT, glucose, calcium, FIB, APTT, PCT, CRP, and FGL-1) were retrospectively analyzed. Results: The plasma FGL-1 levels were increased in both SAP (p < 0.01) and IPN (p < 0.05) subgroups compared to the healthy control group. Multivariate analysis showed that elevated plasma FGL-1 (p < 0.01) and PCT levels (p < 0.05) within 72 h after the onset of AP were positively correlated with the severity of AP, while increased plasma FGL-1 (p < 0.01) and CRP (p < 0.05) levels were positively correlated with the occurrence of IPN. The combination of FGL-1 and PCT showed superiority to both individual markers in SAP prediction. However, the combination of FGL-1 and CRP showed no diagnostic advantage over CRP in IPN prediction. Conclusions: Plasma FGL-1 within 72 h after the onset could be used for the stratification of AP and its infectious complications. The combination of PCT and FGL-1 presents an enormous advantage for the early identification of SAP.

Construction and validation of a prognostic model of pyroptosis related genes in hepatocellular carcinoma.

Pyroptosis plays an important role in the occurrence and development of cancer. We are interested in determining the prognostic value of pyroptosis-related genes in hepatocellular carcinoma (HCC). In this study, we searched the original transcriptome data of The Cancer Genome Atlas (TCGA) and identified the related expressed genes by co-expression analysis. Differentially expressed genes were identified by using univariate analysis, the least absolute shrinkage and selection operator (LASSO) and multivariate analysis to screen for genes related to prognosis of HCC. Ultimately, we established a prognostic model for five genes, namely GSDME, DHX9, TREM2, SQSTM1 and GLMN. Survival analysis showed that the overall survival rate of HCC patients with high risk score was significantly lower than that of HCC patients with low risk score, and this signal could be used as an independent prognostic indicator of HCC. Receiver operating characteristic curve analysis confirmed the accuracy of this prognostic signal, and was further verified in a Gene Expression Omnibus (GEO) dataset (GSE14520) and the International Cancer Genome Consortium (ICGC) databases. In addition, nomograms based on the five identified prognostic genes were established and verified internally in TCGA cohort. Additionally, we also analyzed the gene mutations of the model genes and the correlation between immune cells of the model genes. In summary, this study identified for the first time a 5-gene prognostic signature associated with pyroptosis, which can be used as a promising prognostic biomarker and provide some potentially useful therapeutic targets for HCC.

Evaluation of the Effect of Tobacco Use on Buccal Mucosa Graft Histology.

OBJECTIVE: To assess the effect of tobacco use on oral mucosal tissue harvested for urethroplasty. MATERIALS AND METHODS: Retrospective histologic and immunohistochemical (IHC) evaluation of available buccal mucosa tissue samples from patients that underwent buccal mucosa graft urethroplasty from 2018 to 2020. Patients were asked about tobacco use during pre-operative workup. Patients were counseled on and provided resources to aid in cessation of tobacco use, but surgical cases were not canceled or delayed if patients are unable cease all tobacco use. Patients that ceased use 3 months prior to surgery were considered former users. A single pathologist blinded to the smoking status evaluated the buccal mucosa specimens for histologic changes. Quantitative IHC for p75 and Sox2 were obtained. These investigative markers were selected due to their clear and direct involvement in oral mucosa's regenerative mechanism. Current tobacco users, former users and control patients were compared using ANOVA and Chi-square analyses. RESULTS: Study cohort was 16 current users, 16 former users, 32 controls. Demographics did not differ across the groups. Blinded histologic analysis between all groups found no differences. Pair-wise statistical analysis found greater collagen density in the control group compared to current users (P = .01). No differences were found between former and current users or former users and controls. IHC analysis did not demonstrate any difference in the amount or localization of epithelial stem cell markers. CONCLUSION: Our study of buccal mucosa did not find clear or clinically significant histologic or IHC differences between patients with or without a history of tobacco use.

Sex differences in the intrinsic reading neural networks of Chinese children.

Sex differences in reading performance have been considered a relatively stable phenomenon. However, there is no general agreement about their neural basis, which might be due to that sex differences are largely influenced by age. This paper focuses on the sex differences in the reading-related neural network of Chinese children and its interaction with age. We also attempt to predict reading abilities based on neural network. Fifty-three boys and 56 girls (8.2-14.6 years of age) were recruited. We collected their resting-state fMRI and behavioural data. Restricted sex differences were found in the resting-state reading neural network compared to extensive age by sex interaction effect. Specifically, the interactions between sex and age indicated that with increasing age, girls showed greater connectivity strength between visual orthographic areas and other brain areas within the reading network, while boys showed an opposite trend. After controlling age, the prediction models of reading performance for the girls mainly included interhemispheric connections, while the intrahemispheric connections (particularly the phonological route) mainly contributed to predicting the reading ability for boys. Taken together, these findings suggest that sex differences in reading neural networks are modulated by age. Partialling out age, boys and girls also show the stable sex differences in relationship between reading neural circuit and reading behaviour.

Role of Interleukin-17 in Acute Pancreatitis.

Acute pancreatitis (AP) is a leading cause of death and is commonly accompanied by systemic manifestations that are generally associated with a poor prognosis. Many cytokines contribute to pancreatic tissue damage and cause systemic injury. Interleukin-17 (IL-17) is a cytokine that may play a vital role in AP. Specifically, IL-17 has important effects on the immune response and causes interactions between different inflammatory mediators in the AP-related microenvironment. In this literature review, we will discuss the existing academic understanding of IL-17 and the impacts of IL-17 in different cells (especially in acinar cells and immune system cells) in AP pathogenesis. The clinical significance and potential mechanisms of IL-17 on AP deterioration are emphasized. The evidence suggests that inhibiting the IL-17 cytokine family could alleviate the pathogenic process of AP, and we highlight therapeutic strategies that directly or indirectly target IL-17 cytokines in acute pancreatitis.

Lnc-PFAR facilitates autophagy and exacerbates pancreatic fibrosis by reducing pre-miR-141 maturation in chronic pancreatitis.

Chronic pancreatitis (CP) is described as progressive inflammatory fibrosis of pancreas, accompanied with irreversible impaired endocrine and exocrine insufficiency. Pancreatic stellate cells (PSCs) are widely distributed in the stroma of the pancreas and PSCs activation has been shown as one of the leading causes for pancreatic fibrosis. Our previous study has revealed that autophagy is dramatically activated in CP tissues, which facilitates PSCs activation and pancreatic fibrosis. Long non-coding RNAs (LncRNAs) have been recognized as crucial regulators for fibrosis-related diseases. LncRNAs interact with RNA binding protein or construct competitive endogenous RNA (ceRNA) hypothesis which elicited the fibrotic processes. Until now, the effects of lncRNAs on PSCs activation and pancreatic fibrosis have not been clearly explored. In this study, a novel lncRNA named Lnc-PFAR was found highly expressed in mouse and human CP tissues. Our data revealed that Lnc-PFAR facilitates PSCs activation and pancreatic fibrosis via RB1CC1-induced autophagy. Lnc-PFAR reduces miR-141 expression by suppressing pre-miR-141 maturation, which eventually upregulates the RB1CC1 and fibrosis-related indicators expression. Meanwhile, Lnc-PFAR enhanced PSCs activation and pancreatic fibrosis through trigging autophagy. Our study interrogates a novel lncRNA-induced mechanism in promoting the development of pancreatic fibrosis, and Lnc-PFAR is suggested to be a prospective therapeutic target in clinical scenarios.