Simulation of gradient period polarization volume gratings for augmented reality displays.

Augmented reality (AR) displays are gaining attention as next-generation intelligent display technologies. Diffractive waveguide technologies are progressively becoming the AR display industry's preferred option. Gradient period polarization volume holographic gratings (PVGs), which are considered to have the potential to expand the field of view (FOV) of waveguide display systems due to their wide bandwidth diffraction characteristics, have been proposed as coupling elements for diffraction waveguide systems in recent years. Here, what we believe to be a novel modeling method for gradient period PVGs is proposed by incorporating grating stacking and scattering analysis utilizing rigorous coupled-wave analysis (RCWA) theory. The diffraction efficiency and polarization response were extensively explored using this simulation model. In addition, a dual-layer full-color diffractive waveguide imaging simulation using proposed gradient period PVGs is accomplished in Zemax software using a self-compiled dynamic link library (DLL), achieving a 53° diagonal FOV at a 16:9 aspect ratio. This work furthers the development of PVGs by providing unique ideas for the field of view design of AR display.

Hurricane annual cycle controlled by both seeds and genesis probability.

Understanding tropical cyclone (TC) climatology is a problem of profound societal significance and deep scientific interest. The annual cycle is the biggest radiatively forced signal in TC variability, presenting a key test of our understanding and modeling of TC activity. TCs over the North Atlantic (NA) basin, which are usually called hurricanes, have a sharp peak in the annual cycle, with more than half concentrated in only 3 mo (August to October), yet existing theories of TC genesis often predict a much smoother cycle. Here we apply a framework originally developed to study TC response to climate change in which TC genesis is determined by both the number of pre-TC synoptic disturbances (TC "seeds") and the probability of TC genesis from the seeds. The combination of seeds and probability predicts a more consistent hurricane annual cycle, reproducing the compact season, as well as the abrupt increase from July to August in the NA across observations and climate models. The seeds-probability TC genesis framework also successfully captures TC annual cycles in different basins. The concise representation of the climate sensitivity of TCs from the annual cycle to climate change indicates that the framework captures the essential elements of the TC climate connection.

Interleukin-6 on postoperative day three as an early predictor of infections following laparoscopic gastric cancer resection.

BACKGROUND: To investigate the role of C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) as early predictors of infectious complications after laparoscopic gastric cancer surgery. METHODS: Patients who underwent laparoscopic gastric cancer surgery between January 2020 and June 2022 were retrospectively enrolled. IL-6, PCT, and CRP levels were assessed before surgery and on postoperative days (PODs) 3 and 5. Differences in serum IL-6, PCT, and CRP levels between the infected and non-infected groups were compared. The diagnostic accuracy was determined using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 206 patients were enrolled, and 21 patients (10.19%) developed postoperative infections. Serum IL-6, PCT, and CRP levels in the infected group were significantly higher than those in the non-infected group on PODs 3 and 5. IL-6 with an optimal cutoff value of 84.00 pg/mL (AUC 0.84), PCT with an optimal cutoff value of 1.39 ng/mL (AUC 0.80), CRP with an optimal cutoff value of 150.00 mg/L (AUC 0.76) on POD 3 had superior diagnostic accuracy in predicting postoperative infections. Multivariate analysis identified PCT and IL-6 levels on POD 3 as independent risk factors, the AUC of the combination of IL-6 and PCT was 0.89. The Delong test showed no difference between the AUC of IL-6 alone and IL-6 combined with PCT prediction (P = 0.07, Z = 1.81). CONCLUSIONS: IL-6 level on POD 3 is an excellent predictor of infectious complications following laparoscopic gastric cancer surgery. Patients with IL-6 levels lower than 84.00 pg/mL on POD 3 can ensure safe early discharge with a low probability of infection.

Immune Response Gene-1 [IRG1]/itaconate protect against multi-organ injury via inhibiting gasdermin D-mediated pyroptosis and inflammatory response.

Sepsis is a multiple organ dysfunction syndrome due to a dysregulated response to infection with unacceptably high mortality. Currently, no effective treatment exists for sepsis. IRG1/itaconate has been considered to play a protective role for various inflammatory diseases. In the present study, we explored the protective role and mechanisms of IRG1/itaconate on lipopolysaccharide (LPS)-induced multi-organ injury. The LPS-induced sepsis model was used. IRG1-/- and wild type mice were used to explore the protective role of IRG1/itaconate on multi-organ injury. GSDMD-/- mice were used to explore the effect of GSDMD-mediated pyroptosis on LPS-induced model. RAW264.7 cells and bone-marrow-derived macrophages (BMDMs) were used for in vitro studies. In vivo experiments, we found IRG1 deficiency aggravated LPS-induced multi-organ injury especially lung injury. 4-Octyl itaconate (4-OI), a derivative of itaconate, significantly ameliorated LPS-induced acute lung, liver, and kidney injury. Furthermore, IRG1/4-OI decreased serum interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α) level, macrophage infiltration, and TUNEL-positive cells in lung and liver tissue. Western blot showed IRG1/itaconate decreased the expressions of p-ERK, p-P38, p-JNK, and p-P65 and increased the expression of Nrf2/HO-1 in lung tissue. Meanwhile, 4-OI inhibited the expression of GSDMD-N. In vitro experiments, 4-OI inhibited ROS production and promoted apoptosis under LPS stimulation in RAW264.7 cells. Furthermore, 4-OI inhibited nuclear factor-kappaB/mitogen-activated protein kinase pathways and GSDMD-medicated pyroptosis in BMDMs. Finally, we used GSDMD-/- mice to explore the effect of pyroptosis on LPS-induced multi-organ injury. The results showed that GSDMD deficiency significantly ameliorated lung injury. In conclusion, our data demonstrated that IRG1/itaconate protect against multi-organ injury via inhibiting inflammation response and GSDMD-indicated pyroptosis, which may be a promising agent for protecting against sepsis.

Metabolite itaconate in host immunoregulation and defense.

Metabolic states greatly influence functioning and differentiation of immune cells. Regulating the metabolism of immune cells can effectively modulate the host immune response. Itaconate, an intermediate metabolite derived from the tricarboxylic acid (TCA) cycle of immune cells, is produced through the decarboxylation of cis-aconitate by cis-aconitate decarboxylase in the mitochondria. The gene encoding cis-aconitate decarboxylase is known as immune response gene 1 (IRG1). In response to external proinflammatory stimulation, macrophages exhibit high IRG1 expression. IRG1/itaconate inhibits succinate dehydrogenase activity, thus influencing the metabolic status of macrophages. Therefore, itaconate serves as a link between macrophage metabolism, oxidative stress, and immune response, ultimately regulating macrophage function. Studies have demonstrated that itaconate acts on various signaling pathways, including Keap1-nuclear factor E2-related factor 2-ARE pathways, ATF3-IκBζ axis, and the stimulator of interferon genes (STING) pathway to exert antiinflammatory and antioxidant effects. Furthermore, several studies have reported that itaconate affects cancer occurrence and development through diverse signaling pathways. In this paper, we provide a comprehensive review of the role IRG1/itaconate and its derivatives in the regulation of macrophage metabolism and functions. By furthering our understanding of itaconate, we intend to shed light on its potential for treating inflammatory diseases and offer new insights in this field.

The impact of COVID-19 nonpharmaceutical interventions on the future dynamics of endemic infections.

Nonpharmaceutical interventions (NPIs) have been employed to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet these measures are already having similar effects on other directly transmitted, endemic diseases. Disruptions to the seasonal transmission patterns of these diseases may have consequences for the timing and severity of future outbreaks. Here we consider the implications of SARS-CoV-2 NPIs for two endemic infections circulating in the United States of America: respiratory syncytial virus (RSV) and seasonal influenza. Using laboratory surveillance data from 2020, we estimate that RSV transmission declined by at least 20% in the United States at the start of the NPI period. We simulate future trajectories of both RSV and influenza, using an epidemic model. As susceptibility increases over the NPI period, we find that substantial outbreaks of RSV may occur in future years, with peak outbreaks likely occurring in the winter of 2021-2022. Longer NPIs, in general, lead to larger future outbreaks although they may display complex interactions with baseline seasonality. Results for influenza broadly echo this picture, but are more uncertain; future outbreaks are likely dependent on the transmissibility and evolutionary dynamics of circulating strains.

Hepatoprotective Role of 4-Octyl Itaconate in Concanavalin A-Induced Autoimmune Hepatitis.

4-Octyl itaconate (OI) is a novel anti-inflammatory metabolite that exerts protective effects in many various disease models. However, its function in autoimmune hepatitis- (AIH-) associated hepatic injury has not been investigated. In this study, we successfully used concanavalin A (Con A) to establish an AIH-associated liver injury model. Furthermore, we investigated the effect of OI in Con A-induced liver injury and found that OI mitigated Con A-induced histopathological damage. OI administration reduced serum levels of alanine transaminase and aspartate transaminase in Con A-treated mice and attenuated the infiltration of macrophages induced by Con A. Moreover, OI effectively inhibited the expression of proinflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and IL-1ß induced by Con A. Furthermore, OI decreased hepatocyte apoptosis and malondialdehyde levels and increased the reduced glutathione/oxidized glutathione ratio in the Con A-induced liver injury model. In addition, we found that OI inhibited Con A-induced hepatocyte apoptosis in vitro, while Nrf2 deletion eliminated this effect. Furthermore, we administrated the Nrf2 inhibitor ML385 in OI+Con A-treated mice and found that ML385 eliminated the protective effect of OI in vivo. In addition, OI inhibited Con A-induced activation of nuclear factor-kappa B (NF-𝜅B) and the expression of proinflammatory cytokines in macrophages. Therefore, OI protected mice from Con A-induced liver damage and may be associated with Nrf2 activation and NF-𝜅B inhibition. Finally, our study revealed that OI inhibited TNF-α, or supernatants from Con A-treated RAW264.7 cells induced hepatocyte apoptosis. In conclusion, our study indicated that OI alleviated Con A-induced hepatic damage by reducing inflammatory response, oxidative stress, and apoptosis.

Procalcitonin as an Early Predictor of Intra-abdominal Infections Following Gastric Cancer Resection.

BACKGROUND: The purpose of this study was to investigate the prognostic value of postoperative procalcitonin (PCT) and C-reactive protein (CRP) for their ability to detect Intra-abdominal infections (IAIs) in patients after GC surgery. METHODS: Patients who underwent elective gastrectomy for primary GC were retrospectively enrolled between October 2018 and October 2019. The PCT and CRP levels and white blood cell (WBC) count were measured before surgery and on postoperative days (POD) 1, 3, 5, and 7. The differences in serum PCT, CRP, and WBC levels between IAIs and non-IAIs groups were compared. Diagnostic accuracy was determined by the area under the receiver operating characteristic curve. Univariate and multivariate logistic regression analyses identified independent clinical factors that predicted postoperative IAIs. RESULTS: A total of 155 patients who underwent GC surgery were enrolled. IAIs were observed in 12 patients (7.74%). The postoperative CRP and PCT values in the IAI group were higher than those in the non-IAI group. PCT had superior diagnostic accuracy on POD 3 (area under the curve 0.769) with an optimal cutoff value of 2.03 ng/mL, yielding 75% sensitivity, 87.4% specificity, and 97.6% negative predictive value. Multivariate analysis identified a PCT level of 2.03 mg/mL or greater on POD 3 as a significant predictive factor for IAIs after gastrectomy (odds ratio: 21.447, 95% confidence interval: 5.081-91.672). CONCLUSIONS: PCT values less than 2.03 ng/mL on POD 3 is an excellent negative predictor of IAIs, which may ensure a safe early discharge after gastric cancer surgery.

The effect of neoadjuvant imatinib therapy on outcome and survival in rectal gastrointestinal stromal tumors: A multiinstitutional study.

BACKGROUND AND OBJECTIVES: This study aimed to characterize the efficacy of neoadjuvant imatinib in rectal gastrointestinal stromal tumors (GISTs) and the prognostic characteristics of patients after surgery. METHODS: Patients with rectal GISTs who received neoadjuvant imatinib between 2000 and 2019 were selected from 11 large-scale tertiary hospitals in China. The best response to neoadjuvant imatinib was assessed. Propensity score matching (PSM) was conducted to reduce confounders. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. RESULTS: Of the 100 patients, 75, 18, and 7 had a partial response (PR), stable disease (SD), and progressive disease (PD), respectively. The median tumor size decreased from 5 cm before treatment to 4 cm after treatment (p < 0.001). A total of 31 patients underwent genetic testing after surgery; 23 of patients with exon 11 mutation had PR and 2 had SD. One of the patients with exon 9 mutation had PR, 2 had SD, and 1 had PD. Two patients with the wild type GIST had PD. A total of 86 patients underwent surgery of which 85 underwent complete resection; 72 underwent anal preservation and 40 underwent local excision (LE). After PSM, patients who received neoadjuvant therapy had higher rates of LE (p = 0.001) and anal preservation (p = 0.033) than those of patients without neoadjuvant therapy. The median follow-up time was 37 months. Nine patients experienced recurrence and one patient died. The 3-year RFS and OS rates were 95.0% and 100%, respectively. After PSM, we found that there was no significant difference in RFS between patients who received or did not receive neoadjuvant therapy (p = 0.623). Univariate analysis showed postneoadjuvant tumor size (p = 0.469) and mitotic count (p = 0.294) were not associated with the RFS in patients who received neoadjuvant imatinib. CONCLUSIONS: Neoadjuvant imatinib can shrink rectal GIST size, increasing the possibility of complete resection and anal preservation. Further studies are warranted to understand the long-term outcomes of rectal GISTs in patients receiving neoadjuvant imatinib.

Elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis of patients with primary gastrointestinal stromal tumor.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are considered to reflect the systemic inflammatory response and clinical prognosis. However, the independent prognostic values of the NLR and PLR for patients with gastrointestinal stromal tumor (GIST) remain debatable. This study aims to evaluate the prognostic value of preoperative NLR and PLR in GIST patients. METHODS: We retrospectively reviewed all GIST patients diagnosed and surgically treated at Union Hospital between 2005 and 2018. The preoperative NLR and PLR were calculated to evaluate recurrence-free survival (RFS) and overall survival (OS) by Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were performed to estimate the independent prognostic values. RESULTS: The median follow-up time was 49 months (interquartile range, 22-74 months). The preoperative PLR was significantly increased in the GIST patients with intermediate and high tumor risks. Increases in the NLR (≥2.34) and PLR (≥185.04) were associated with shorter RFS and OS (P < 0.01). Moreover, the multivariate analysis revealed that elevated PLR was an independent factor for shorter RFS (hazard ratio [HR]: 3.041; 95% confidence interval [CI]: 2.001-4.622; P < 0.001) and OS (HR: 1.899; 95% CI: 1.136-3.173; P = 0.014). CONCLUSIONS: The preoperative PLR is a potential biomarker of GIST and is related to the clinical outcome. An elevated preoperative PLR predicts poor prognosis of patients with primary GIST after complete surgical resection.

Targeting the WEE1 kinase strengthens the antitumor activity of imatinib via promoting KIT autophagic degradation in gastrointestinal stromal tumors.

BACKGROUND: Activating mutation of KIT or PDGFRA is the primary molecular mechanism for gastrointestinal stromal tumors (GISTs). Although imatinib has a revolutionary effect on GIST therapeutics, the benefits are not durable. Increasing reports have demonstrated that cell cycle checkpoint plays critical roles in GIST. Here, we explore the role of WEE1 kinase in GIST progression. METHODS: Oncomine public database, western blotting, and immunohistochemistry were used to analyze WEE1 expression in GISTs. Using MTT assays, colony formation analysis, and flow cytometry, we examined the role of WEE1 in GIST cells and the antitumor activity of the inhibitor MK1775 alone, or in combination with imatinib. Cycloheximide chase assay and pharmacological inhibition of autophagy and proteasome pathway were performed to analyze KIT expression. Additionally, autophagic markers Beclin1 and LC3B were detected by western blotting. RESULTS: Upregulated WEE1 expression was observed in GIST tissues and correlated with tumor size, mitotic count, and risk grade. Inhibition of WEE1 significantly suppressed GIST cell proliferation, induced apoptosis and cell cycle arrest. Imatinib and MK1775 co-treatment markedly enhanced the antitumor activity. Targeting WEE1 decreased the expression of KIT expression. Moreover, WEE1 stabilized KIT protein and KIT reduction observed upon WEE1 inhibition could be reversed by pharmacological inhibition of autophagy, but not proteasome pathway. WEE1 inhibition also increased Beclin1 expression and LC3B II/I ratio in GIST cells. CONCLUSIONS: Our data suggest that WEE1 plays a pivotal role in GIST proliferation. WEE1 inhibition could promote KIT autophagic degradation and, therefore, targeting WEE1 might represent a novel strategy for GIST therapies.

Tert-butylhydroquinone mitigates Carbon Tetrachloride induced Hepatic Injury in mice.

Tert-butylhydroquinone (tBHQ) is an antioxidant compound that exhibits cytoprotective effect in many tissues under pathological condition. However, its role in carbon tetrachloride (CCL4) induced liver injury is still unclear. Here we established a carbon tetrachloride induced hepatic injury model in mice to determine whether tBHQ can mitigate CCL4 induced liver damage. In our study, we found tBHQ exhibited protective effects in CCL4 treated mice model. TBHQ markedly improved hepatic function and decreased hepatic histopathological damage in vivo. In addition, tBHQ reduced levels of pro-inflammatory cytokines in mice model. Moreover, tBHQ mitigated apoptosis of hepatocytes, oxidative stress and lipid peroxidation in vivo and in vitro. We also found the possible mechanism of protective effects of tBHQ was associated with activation of Nrf2/ heme oxygenase-1 (HO-1) pathway. In conclusion, our study revealed tBHQ can be a potential therapeutic drug in treatment of acute hepatic injury.

Prognostic Value of Surgical Site Infection in Patients After Radical Colorectal Cancer Resection.

BACKGROUND This study aimed to evaluate the clinicopathological factors associated with surgical site infection (SSI) and the prognostic impact on patients after colorectal cancer (CRC) resection surgery. MATERIAL AND METHODS This retrospective study evaluated the relationships between SSI and various clinicopathological factors and prognostic outcomes in 326 consecutive patients with CRC who underwent radical resection surgery at Wuhan Union Hospital during April 2015-May 2017. RESULTS Among the 326 patients who underwent radical CRC resection surgery, 65 had SSIs, and the incidence rates of incisional and organ/space SSI were 16.0% and 12.9%, respectively. Open surgery, chronic obstructive pulmonary disease (COPD), and a previous abdominal surgical history were identified as risk factors for incisional SSI. During a median follow-up of 40 months (range: 5-62 months), neither simple incisional nor simple organ/space SSI alone significantly affected disease-free survival (DFS) or overall survival (OS), whereas combined incisional and organ/space SSI had a significant negative impact on both the 3-year DFS and OS (P<0.001). A multivariate analysis identified that age ≥60 years, lymph node involvement, tumor depth (T3-T4), and incisional and organ/space SSI were independent predictors of 3-year DFS and OS. In addition, adjuvant chemotherapy and a carbohydrate antigen-125 concentration ≥37 ng/ml were also independent predictors of OS. CONCLUSIONS We have identified several clinicopathological factors associated with SSI, and identified incisional and organ/space SSI is an independent prognostic factor after CRC resection. Assessing the SSI classification may help to predict the prognosis of these patients and determine further treatment options.

Research on Focal Length Measurement Scheme of Self-Collimating Optical Instrument Based on Double Grating.

In this paper, we propose a scheme for measuring the focal length of a collimating optical instrument. First, a mathematical model for measuring the focal length of a collimator with double gratings is derived based on the moiré fringe formula and the principles of geometric optics. Mathematical simulation shows that a slight difference in the focal length of two collimators has an important influence on the imaging law of moiré fringes. Our solution has a good resolution ability for focal length differences within 5‱, especially in the small angle range below 4°. Thus, the focal length of collimators can be measured by the amplification of the slight difference. Further, owing to the relative reference measurement, the measurement resolution at the symmetrical position of focal length is poor. Then, in the designed experiment, a corresponding moiré image at different angles is acquired using collimators with known focal length. The experimental results indicate that the root mean square error (RMSE) of the collimator corresponding to grating angles of 2°-4° is better than 4.7‱, indicating an ideal measurement accuracy of the proposed scheme. This work demonstrates that our proposed scheme can achieve an ideal accuracy in the measurement of a symmetrical optical path.

A Novel Model Predicts Postoperative Pathology of Colorectal High-Grade Intraepithelial Neoplasia.

BACKGROUND: To analyze the consistency of endoscopic biopsy of colorectal high-grade intraepithelial neoplasia (HGIN) and pathological diagnosis and to explore the value of preoperative examination in differentiating HGIN from invasive carcinoma. METHODS: Clinicopathological data of 79 patients with colorectal HGIN undergoing preoperative endoscopic biopsy from January 2012 to December 2017 were retrospectively analyzed. RESULTS: Pathologically, 57 cases (72.8%) were diagnosed as invasive carcinoma and 22 (27.8%) as HGIN. Tumor size ≥3 cm, ulcer on the surface of the lesion, HGIN without adenoma, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, lymph node enlargement, and spiculation of the peri-intestinal fat on computed tomography were associated with postoperative invasive carcinoma. Multivariate analysis showed that a longest diameter ≥3 cm, preoperative diagnosis of HGIN without adenoma, and spiculation of the peri-intestinal fat were independent factors for a postoperative diagnosis of invasive carcinoma. Depending on the weight of these three independent factors in binary logistic regression analysis, a comprehensive scoring model was established. When the score was ≥1.5, the sensitivity and specificity for the diagnosis of invasive carcinoma were 86.0% and 81.8%, respectively. Utilizing the prediction index, the area under the receiver operating characteristic curve was 0.869. CONCLUSIONS: A diagnosis of colorectal HGIN by colonoscopy is poorly consistent with the postoperative pathological diagnosis. The scoring model established in this study for identifying colorectal infiltrating carcinoma is simple and feasible. When the comprehensive score is ≥ 1.5, an aggressive approach of surgical treatment is recommended.

Development and evaluation of a genetic algorithm-based ocean color inversion model for simultaneously retrieving optical properties and bottom types in coral reef regions.

This work presents a novel approach that integrates a shallow water semi-analytical (SSA) model and a genetic algorithm (GA) to retrieve water column inherent optical properties (IOPs) and identify bottom types simultaneously from measurement of subsurface remote sensing reflectance. This GA-SSA approach is designed based on the assumption that each pixel is homogeneous with regard to the bottom type when viewed at small (centimeter) scales, and it is validated against a synthetic data set (N=11,250) that consists of five types of bottom, three levels of bottom depth, 15 concentrations of chlorophyll-a (Chl-a), and a wide range of modeled IOP variations in clear and optically complex waters representing the coral reef environment. The results indicate that the GA-SSA approach is accurate and robust in the retrieval of IOPs and its success rate in identifying the real bottom type is limited by the level of Chl-a and bottom depth. When a pixel is homogeneous at a small scale, the maximum allowable concentrations for GA-SSA to perfectly identify all the five bottom types are 0.7 mg/m3 at 5 m bottom depth, 0.2 mg/m3 at 10 m, and 0.07 mg/m3 at 15 m. A promising 80% recognition rate of the benthic community is possible with GA-SSA when an underwater hyperspectral imager is deployed to examine the health status of coral reefs in a clean (Chl-a<1 mg/m3) and shallow (bottom depth<10 m) environment. Further study that collects field data for direct validation is required to ensure that the GA-SSA approach is also applicable in real coral reef regions.

Development and Validation of a Novel Nomogram Model for Early Diagnosis of Anastomotic Leakage After Laparoscopic Colorectal Cancer Surgery.

Background: This study aimed to investigate the clinical value of inflammatory factors for predicting anastomotic leakage (AL) after laparoscopic colorectal cancer surgery and establish a nomogram model to assess the probability of its occurrence. Patients and Methods: Data of 637 patients who underwent laparoscopic colorectal cancer surgery between June 2019 and June 2022 were collected. Differences in procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) levels before surgery and on postoperative day (POD) 3 and 5 were compared between patients with and without AL (AL and non-AL groups, respectively). The diagnostic accuracy was determined using the area under the receiver operating characteristic curve (AUC), and a nomogram model was developed. Results: Post-operative AL occurred in 46 (7.2%) patients. Procalcitonin, CRP, and WBC levels on POD 3 and 5 were higher in the AL group than in the non-AL group. The AUCs of PCT, CRP, and WBC levels for predicting AL on POD 3 were 0.833, 0.757, and 0.756, respectively, which were better than those on POD 5 (AUC = 0.669, 0.581, and 0.588, respectively). The nomogram model for AL was developed based on five variables (PCT, CRP, WBC, American Society of Anesthesiologists [ASA] grade and comorbidities), and it had an AUC of 0.922. Calibration curves demonstrated that the nomogram had good fit. The Delong test showed that the AUC of the nomogram for predicting the probability of AL was higher than that of PCT alone (z = 2.311, p = 0.02). Conclusions: Procalcitonin measured on POD 3 seems to be a promising negative predictor of AL after laparoscopic colorectal cancer surgery. Furthermore, the nomogram model developed in our study, which utilizes a series of predictors that can be easily accessed, has demonstrated potential to further improve the prediction accuracy.

Efficacy and safety of intravitreal injection of conbercept for moderate to severe nonproliferative diabetic retinopathy.

Purpose: This study aimed to assess the effectiveness and safety of intravitreal injection of conbercept (IVC) in treating moderate to severe nonproliferative diabetic retinopathy (NPDR), with or without accompanying diabetic macular edema. Methods: In this longitudinal retrospective study, 35 patients (50 eyes) with moderate to severe NPDR and Diabetic Retinopathy Severity Scale (DRSS) scores between 43 and 53 were treated at the Department of Ophthalmology, First Affiliated Hospital of Kunming Medical University, from October 2018 to January 2023. Treatment protocol included three monthly IVC injections followed by a pro re nata (PRN) regimen over a two-year follow-up period. Outcome measures were best-corrected visual acuity (BCVA), intraocular pressure, central macular thickness (CMT), extent of hard exudate (HE), and changes in DRSS scores. DRSS scores before and after treatment were analyzed using the Wilcoxon rank-sum test. Both systemic and ocular adverse events were meticulously documented to ascertain safety. Results: From baseline to the final follow-up, the mean BCVA improved from 0.41 ± 0.39 to 0.23 ± 0.20 logMAR (p<0.05). The mean CMT decreased from 306.22 ± 77.40 to 297.97 ± 88.15 µm (p = 0.385). At 24 months, DRSS scores improved by ≥1 stage in 40 eyes (80%), ≥ 2 stages in 28 eyes (56%), ≥3 stages in 10 eyes (20%), and remained stable in 6 eyes (12%). The DRSS scores at each follow-up interval demonstrated statistically significant improvement from baseline (p<0.05). In 15 of 27 eyes (55.56%) with diabetic macular edema (DME), there was a significant reduction in the mean area of HE from baseline (p<0.05). No serious systemic adverse events were observed. Conclusion: IVC is an effective and safe treatment for moderate to severe NPDR, demonstrating significant improvements in DRSS scores.

Last millennium hurricane activity linked to endogenous climate variability.

Despite increased Atlantic hurricane risk, projected trends in hurricane frequency in the warming climate are still highly uncertain, mainly due to short instrumental record that limits our understanding of hurricane activity and its relationship to climate. Here we extend the record to the last millennium using two independent estimates: a reconstruction from sedimentary paleohurricane records and a statistical model of hurricane activity using sea surface temperatures (SSTs). We find statistically significant agreement between the two estimates and the late 20th century hurricane frequency is within the range seen over the past millennium. Numerical simulations using a hurricane-permitting climate model suggest that hurricane activity was likely driven by endogenous climate variability and linked to anomalous SSTs of warm Atlantic and cold Pacific. Volcanic eruptions can induce peaks in hurricane activity, but such peaks would likely be too weak to be detected in the proxy record due to large endogenous variability.

Protective effects of IRG1/itaconate on acute colitis through the inhibition of gasdermins-mediated pyroptosis and inflammation response.

Inflammatory bowel disease (IBD) is a chronic relapsing gastrointestinal disorder, while the treatment effect is not satisfactory. Immune responsive gene 1 (IRG1) is a highly expressed gene in macrophage in response to inflammatory response and catalyzes the production of itaconate. Studies have reported that IRG1/itaconate has a significant antioxidant effect. This study aimed to investigate the effect and mechanism of IRG1/itaconate on dextran sulfate sodium (DSS)-induced colitis in vivo and in vitro. In vivo experiments, we found IRG1/itaconate exerted protective effects against acute colitis by increasing mice weight, the length of colon, reducing disease activity index and colonic inflammation. Meanwhile, IRG1 deletion aggravated the macrophages/CD4+/CD8+ T-cell accumulation, and increased the release of interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), IL-6, the activation of nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, and gasdermin D (GSDMD) mediated pyroptosis. Four-octyl itaconate (4-OI), a derivative of itaconate, attenuated these changes, therefore relieved DSS-induced colitis. In vitro experiment, we found 4-OI inhibited the reactive oxygen species production, thereby inhibiting the activation of MAPK/NF-κB signaling pathway in RAW264.7 and murine bone-marrow-derived macrophages. Simultaneously, we found 4-OI inhibited caspase1/GSDMD-mediated pyroptosis to reduce the release of cytokines. Finally, we found anti-TNF-α agent reduced the severity of DSS-induced colitis and inhibited gasdermin E (GSDME)-mediated pyroptosis in vivo. Meanwhile, our study revealed that 4-OI inhibited caspase3/GSDME-mediated pyroptosis induced by TNF-α in vitro. Taken together, IRG1/itaconate exerted a protective role in DSS-induced colitis by inhibiting inflammatory response and GSDMD/GSDME-mediated pyroptosis, which could be a promising candidate for IBD therapy.