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Introduction: Prophylactic antifungal therapy has been widely used for critical patients, but it has failed to improve patient prognosis and has become a hot topic. This may be related to disruption of fungal homeostasis, but the mechanism of fungi action is not clear. As a common pathway in critical patients, intestinal ischemia–reperfusion (IIR) injury is fatal and regulated by gut microbiota. However, the exact role of enteric fungi in IIR injury remains unclear. Objectives: This is a clinical study that aims to provide new perspectives in clarifying the underlying mechanism of IIR injury and propose potential strategies that could be relevant for the prevention and treatment of IIR injury in the near future. Methods: ITS sequencing was performed to detect the changes in fungi before and after IIR injury. The composition of enteric fungi was altered by pretreatment with single-fungal strains, fluconazole and mannan, respectively. Intestinal morphology and function impairment were evaluated in the IIR injury mouse model. Intestinal epithelial MODE-K cells and macrophage RAW264.7 cells were cultured for in vitro tests. Results: Fecal fungi diversity revealed the obvious alteration in IIR patients and mice, accompanied by intestinal epithelial barrier dysfunction. Fungal colonization and mannan supplementation could reverse intestinal morphology and function impairment that were exacerbated by fluconazole via inhibiting the expression of SAA1 from macrophages and decreasing pyroptosis of intestinal epithelial cells. Clodronate liposomes were used to deplete the number of macrophages, and it was demonstrated that the protective effect of mannan was dependent on macrophage involvement. Conclusion: This finding firstly validates that enteric fungi play a crucial role in IIR injury. Preventive antifungal treatment should consider damaging fungal balance. This study provides a novel clue to clarify the role of enteric fungi in maintaining intestinal homeostasis.

Background We aimed to compare the cardiovascular events and mortality in patients who underwent either physician-oriented or patient-oriented kidney replacement therapy (KRT) conversion due to discontinuation of peritoneal dialysis (PD).Methods Patients with end-stage kidney disease who were receiving PD and required a switch to an alternative KRT were included. They were divided into physician-oriented group or patient-oriented group based on the decision-making process. Logistic regression analysis was used to explore the influencing factors related to KRT conversion in PD patients. The association of physician-oriented or patient-oriented KRT conversion with outcomes after the conversion was assessed by using Cox proportional hazards models.Results A total of 257 PD patients were included in the study. The median age at catheterization was 35 years. 69.6% of the participants were male. The median duration of PD was 20 months. 162 participants had patient-oriented KRT conversion, while 95 had physician-oriented KRT conversion. Younger patients, those with higher education levels, higher income, and no diabetes were more likely to have patient-oriented KRT conversion. Over a median follow-up of 39 months, 40 patients experienced cardiovascular events and 16 patients died. Physician-oriented KRT conversion increased nearly 3.8-fold and 4.0-fold risk of cardiovascular events and death, respectively. After adjusting for confounders, physician-oriented KRT conversion remained about a 3-fold risk of cardiovascular events.Conclusion Compared to patient-oriented KRT conversion, PD patients who underwent physician-oriented conversion had higher risks of cardiovascular events and all-cause mortality. Factors included age at catheterization, education level, annual household income, and history of diabetes mellitus.

Abstract Background More accurate prediction of distant metastases (DM) in patients with colorectal cancer (CRC) would optimize individualized treatment and follow‐up strategies. Multiple prediction models based on machine learning have been developed to assess the likelihood of developing DM. Methods Clinicopathological features of patients with CRC were obtained from the National Cancer Center (NCC, China) and the Surveillance, Epidemiology, and End Results (SEER) database. The algorithms used to create the prediction models included random forest (RF), logistic regression, extreme gradient boosting, deep neural networks, and the K‐Nearest Neighbor machine. The prediction models' performances were evaluated using receiver operating characteristic (ROC) curves. Results In total, 200,958 patients, 3241 from NCC and 197,717 CRC from SEER were identified, of whom 21,736 (10.8%) developed DM. The machine‐learning‐based prediction models for DM were constructed with 12 features remaining after iterative filtering. The RF model performed the best, with areas under the ROC curve of 0.843, 0.793, and 0.806, respectively, on the training, test, and external validation sets. For the risk stratification analysis, the patients were separated into high‐, middle‐, and low‐risk groups according to their risk scores. Patients in the high‐risk group had the highest incidence of DM and the worst prognosis. Surgery, chemotherapy, and radiotherapy could significantly improve the prognosis of the high‐risk and middle‐risk groups, whereas the low‐risk group only benefited from surgery and chemotherapy. Conclusion The RF‐based model accurately predicted the likelihood of DM and identified patients with CRC in the high‐risk group, providing guidance for personalized clinical decision‐making.

Abstract Introduction This study aimed to compare the short-term and survival outcomes in laparoscopic low rectal cancer surgery with three different specimen extraction techniques, and whether it affects loop ileostomy closure. Materials and methods A consecutive series of patients with low rectal cancer who underwent laparoscopic low anterior resection plus protective loop ileostomy (LAR-PLI) were enrolled. Three main techniques, namely specimen extraction through auxiliary incision (EXAI), specimen extraction through stoma incision (EXSI), and specimen eversion and extra-abdominal resection (EVER), were employed. The postoperative short-term and survival outcomes of the three techniques and the impact on loop ileostomy closure were compared. Results In all, 254 patients were enrolled in this study: 104 (40.9%) in the EXAI group, 104 (40.9%) in the EXSI group, and 46 (18.1%) in the EVER group. For primary surgery, EXAI group had significantly longer operative time (P

For the rapid development of the cruise industry, the cruise disaster relief supply chain has attracted extensive attention, especially because COVID-19 cases on international cruise ships occurred. In this paper, we propose an idea of coordination layout for cruise ship emergency supplies, the problem optimized two objective functions of maximizing coverage satisfaction and minimizing the total cost, addressing the low efficiency of resource utilization at the same. By applying to cruise ship emergency supplies layout of Northeast Asia cruise port group system, using expert scoring method and AHP to evaluate cruise port security vulnerability. The NSGA-II algorithm is used to solve the multi-objective programming model. A numerical example shows that the optimization design model and method are valid and feasible, and the algorithm is efficient for solving the above collaborative location and allocation problem of sectional reserves, which can also offer a variety of decision-making options.

Ischemic-reperfusion injury (IRI) is a major pathogenic factor in acute kidney injury (AKI), which directly leads to the hypoxic injury of renal tubular epithelial cells (RTECs). Although emerging studies suggest repressor element 1–silencing transcription factor (REST) as a master regulator of gene repression under hypoxia, its role in AKI remains elusive. Here, we found that REST was upregulated in AKI patients, mice, and RTECs, which was positively associated with the degree of kidney injury, while renal tubule–specific knockout of Rest significantly alleviated AKI and its progression to chronic kidney disease (CKD). Subsequent mechanistic studies indicated that suppression of ferroptosis was responsible for REST-knockdown-induced amelioration of hypoxia-reoxygenation injury, during which process Cre-expressing adenovirus–mediated REST downregulation attenuated ferroptosis through upregulating glutamate-cysteine ligase modifier subunit (GCLM) in primary RTECs. Further, REST transcriptionally repressed GCLM expression via directly binding to its promoter region. In conclusion, our findings revealed the involvement of REST, a hypoxia regulatory factor, in AKI-to-CKD transition and identified the ferroptosis-inducing effect of REST, which may serve as a promising therapeutic target for ameliorating AKI and its progression to CKD.

Transverse colon cancer accounts for about 10% of all colonic cancers. The resection of cancers in the transverse colon is technically more challenging, compared with other cancer locations in the colon because the variable anatomy of the middle colic vessels demands excellent surgical skills and the anatomical location of the transverse colon is related to major organs. We report a novel laparoscopic technique for the first time used in surgery of transverse colon cancer which combines a total intracorporeal anastomosis with natural orifice specimen extraction to solve the problems of traditional laparoscopic surgery. A 48-year-old male patient, whose diagnosis was transverse colon adenocarcinoma, was admitted to the hospital. The surgery was performed in accordance with the procedure of totally laparoscopic right hemicolectomy and the specimen was extracted by opening the rectum. Natural orifice specimen extraction surgery has many advantages, including less pain, better cosmesis and minimising risks of complications and also has comparable long-term outcomes compared to conventional laparoscopic surgery.

BackgroundProgrammed cell death protein 1 (PD-1) receptor has two ligands,programmed death-ligand 1 (PD-L1) and PD-L2. When compared with PD-L1, PD-L2 has not received much attention, and its role remains unclear.MethodsThe expression profiles of pdcd1lg2 (PD-L2-encoding gene) mRNA and PD-L2 protein were analyzed using TCGA, ICGC, and HPA databases. Kaplan-Meier and Cox regression analyses were used to assess the prognostic significance of PD-L2. We used GSEA, Spearman’s correlation analysis and PPI network to explore the biological functions of PD-L2. PD-L2-associated immune cell infiltration was evaluated using the ESTIMATE algorithm and TIMER 2.0. The expressions of PD-L2 in tumor-associated macrophages (TAMs) in human colon cancer samples, and in mice in an immunocompetent syngeneic setting were verified using scRNA-seq datasets, multiplex immunofluorescence staining, and flow cytometry. After fluorescence-activated cell sorting, flow cytometry and qRT-PCR and transwell and colony formation assays were used to evaluate the phenotype and functions of PD-L2+TAMs. Immune checkpoint inhibitors (ICIs) therapy prediction analysis was performed using TIDE and TISMO. Last, a series of targeted small-molecule drugs with promising therapeutic effects were predicted using the GSCA platform.ResultsPD-L2 was expressed in all the common human cancer types and deteriorated outcomes in multiple cancers. PPI network and Spearman’s correlation analysis revealed that PD-L2 was closely associated with many immune molecules. Moreover, both GSEA results of KEGG pathways and GSEA results for Reactome analysis indicated that PD-L2 expression played an important role in cancer immune response. Further analysis showed that PD-L2 expression was strongly associated with the infiltration of immune cells in tumor tissue in almost all cancer types, among which macrophages were the most positively associated with PD-L2 in colon cancer. According to the results mentioned above, we verified the expression of PD-L2 in TAMs in colon cancer and found that PD-L2+TAMs population was not static. Additionally, PD-L2+TAMs exhibited protumor M2 phenotype and increased the migration, invasion, and proliferative capacity of colon cancer cells. Furthermore, PD-L2 had a substantial predictive value for ICIs therapy cohorts.ConclusionPD-L2 in the TME, especially expressed on TAMs, could be applied as a potential therapeutic target.

The air quality in China has been improved substantially, however fine particulate matter (PM2.5) still remain at a high level in many areas. PM2.5 pollution is a complex process that is attributed to gaseous precursors, chemical, and meteorological factors. Quantifying the contribution of each variable to air pollution can facilitate the formulation of effective policies to precisely eliminate air pollution. In this study, we first used decision plot to map out the decision process of the Random Forest (RF) model for a single hourly data set and constructed a framework for analyzing the causes of air pollution using multiple interpretable methods. Permutation importance was used to qualitatively analyze the effect of each variable on PM2.5 concentrations. The sensitivity of secondary inorganic aerosols (SIA): SO42-, NO3- and NH4+ to PM2.5 was verified by Partial dependence plot (PDP). Shapley Additive Explanation (Shapley) was used to quantify the contribution of drivers behind the ten air pollution events. The RF model can accurately predict PM2.5 concentrations, with determination coefficient (R2) of 0.94, root mean square error (RMSE) and mean absolute error (MAE) of 9.4 μg/m3 and 5.7 μg/m3, respectively. This study revealed that the order of sensitivity of SIA to PM2.5 was NH4+＞NO3-＞SO42-. Fossil fuel and biomass combustion may be contributing factors to air pollution events in Zibo in 2021 autumn–winter. NH4+ contributed 19.9–65.4 μg/m3 among ten air pollution events (APs). K, NO3-, EC and OC were the other main drivers, contributing 8.7 ± 2.7 μg/m3, 6.8 ± 7.5 μg/m3, 3.6 ± 5.8 μg/m3 and 2.5 ± 2.0 μg/m3, respectively. Lower temperature and higher humidity were vital factors that promoted the formation of NO3-. Our study may provide a methodological framework for precise air pollution management.

PurposeTotal laparoscopic anterior resection (tLAR) has been gradually applied in the treatment of rectal cancer (RC). This study aims to develop a scoring system to predict the surgical difficulty of tLAR.MethodsRC patients treated with tLAR were collected. The blood loss and duration of excision (BLADE) scoring system was built to assess the surgical difficulty by using restricted cubic spline regression. Multivariate logistic regression was used to evaluate the effect of the BLADE score on postoperative complications. The random forest (RF) algorithm was used to establish a preoperative predictive model for the BLADE score.ResultsA total of 1,994 RC patients were randomly selected for the training set and the test set, and 325 RC patients were identified as the external validation set. The BLADE score, which was built based on the thresholds of blood loss (60 ml) and duration of surgical excision (165 min), was the most important risk factor for postoperative complications. The areas under the curve of the predictive RF model were 0.786 in the training set, 0.640 in the test set, and 0.665 in the external validation set.ConclusionThis preoperative predictive model for the BLADE score presents clinical feasibility and reliability in identifying the candidates to receive tLAR and in making surgical plans for RC patients.

In order to meet the processing requirements of large aerospace thin-walled curved workpieces，a five-degree-of-freedom （5-DOF） hammer riveting robot is designed. In view of the characteristics of the 5-DOF hammer riveting robot， combining Lie group Lie algebra and spiral theory， its kinematics model is established and solved； use the exponential product formula to derive the Jacobian matrix of the robot，and use the stiffness mapping theory to solve the stiffness matrix of the robot； the finite element and Matlab simulation software are used to simulate and verify the end deformation under the general pose and the extreme pose，and the stiffness distribution map of the robot in the task space varying with the change of pose is given；the simulation result is compared with the theoretical calculation value and the error is not more than 10%，which verify the correctness and effectiveness of the established stiffness model and provide important reference for optimization of subsequent work path.

The mechanical properties of sclera play an important role in ocular functions, protection, and disease. Modulating the sclera's properties by exogenous crosslinking offers a way to expand the tissue's range of properties for study of the possible influences on the eye's behavior and diseases such as glaucoma and myopia. The focus of this work was to evaluate the effects of genipin crosslinking targeting the porcine perilimbal sclera (PLS) since the stiffness of this tissue was previously found in a number of studies to influence the eye's intraocular pressure (IOP). The work includes experiments on tensile test specimens and whole globes. The specimen tests showed decreased strain-rate dependence and increased relaxation stress due to the cross-linker. Whole globe perfusion experiments demonstrated that eyes treated with genipin in the perilimbal region had increased IOPs compared to the control globes. Migration of the cross-linker from the target tissue to other tissues is a confounding factor in whole globe, biomechanical measurements, with crosslinking. A novel quantitative genipin assay of the trabecular meshwork (TM) was developed to exclude globes where the TM was inadvertently crosslinked. The perfusion study, therefore, suggests that elevated stiffness of the PLS can significantly increase IOP apart from effects of the TM in the porcine eye. These results demonstrate the importance of PLS biomechanics in aqueous outflow regulation and support additional investigations into the distal outflow pathways as a key source of outflow resistance. [ABSTRACT FROM AUTHOR]

The measurement and control of mechanical resonators are critical for cavity magnomechanics, which has emerged as an important frontier for hybrid quantum systems based on magnonics. Traditional microwave-based measurements require handling high-frequency signals and cannot achieve field distribution detection. Here, we demonstrate a method for optically measuring and manipulating a ferromagnetic mechanical resonator. This technique allows for direct observation of the response and field distribution of mechanical oscillations during magnomechanically induced transparency/absorption processes, confirming that the mechanical mode S 1 , 2 is coupled with the magnon. The optical measurement not only serves to validate the magnomechanical coupling theory but also reduces the necessity for high-frequency measurements. Furthermore, we utilize the instantaneously measured results to implement feedback control of the self-oscillating mechanical resonator to overcome the dynamical back-action limit, achieving a threefold enhancement of phonon lasing amplitude. This feedback control lays the foundation for the study of quantum cavity magnomechanics, such as the feedback cooling of a magnomechanical resonator. [ABSTRACT FROM AUTHOR]

PurposeRecently, totally laparoscopic ileostomy reversal (TLAP) has received increasing attention and exhibited promising short-term outcomes. The aim of this study was to detail the learning process of the TLAP technique.MethodsBased on our initial experience with TLAP from 2018, a total of 65 TLAP cases were enrolled. Demographics and perioperative parameters were assessed using cumulative sum (CUSUM), moving average, and risk-adjusted CUSUM (RA-CUSUM) analyses.ResultsThe overall mean operative time (OT) was 94 min and the median postoperative hospitalization period was 4 days, and there was an estimated 10.77% incidence rate of perioperative complications. Three unique phases of the learning curve were derived from CUSUM analysis, and the mean OT of phase I (1–24 cases) was 108.5 min, that of phase II (25–39 cases) was 92 min, and that of phase III (40–65 cases) was 80 min, respectively. There was no significant difference in perioperative complications between these 3 phases. Similarly, moving average analysis indicated that the operation time was reduced significantly after the 20th case and reached a steady state after the 36th case. Furthermore, complication-based CUSUM and RA-CUSUM analyses indicated an acceptable range of complication rates during the whole learning period.ConclusionOur data demonstrated 3 distinct phases of the learning curve of TLAP. For an experienced surgeon, surgical competence in TLAP can be grasped at around 25 cases with satisfactory short-term outcomes.

In conventional sequence stratigraphy research, owing to the limitation of the resolution of seismic data, strata can only be divided into third order sequences at most on the seismic profile. In this study, the vertical fourth order sequence is divided using the high vertical resolutions of gamma ray (GR), uranium (U), thorium (Th), and potassium (K) curves in the logging curves, and the sequence divided in the depth system is then accurately superimposed on the seismic profile through one dimensional forward modelling. Subsequently, through three dimensional Fourier transform technology, the dip angle and azimuth information of the seismic data in the entire region are scanned to obtain the horizons. Through the progradation and retrogradation characteristics of sediments in the Wheeler system, guided by the sequence framework, the horizontal interpretation of the fourth order sequence system tract is conducted in the entire region. Finally, through attribute optimisation, the root mean square amplitude attribute, with the highest degree of coincidence with well data, is selected to study the evolution characteristics of sedimentary microfacies in different periods in the four system tracts. Notably, the strata of Qixia Formation in the study area can be divided into two-fourth order sequences, wherein SQ1 comprised transgressive systems tract 1 (TST1) and high stand systems tract 1 (HST1), and SQ2 comprised TST2 and HST2. With the change in the relative sea level cycle, the strata of Qixia Formation in the study area are developed by overlapping the sedimentary microfacies of the interbank depression, interbank sea, and intraplatform shoal from bottom to top.

Recommender systems are devoted to find and automatically recommend valuable information and services for users from massive data,which can effectively solve the information overload problem,and become an important information technology in the era of big data.However,the problems of data sparsity,cold start,and interpretability are still the key technical difficulties that limit the wide application of the recommender systems.Reinforcement learning is an interactive learning technique,which can dynamically model user preferences by interacting with users and obtaining feedback to capture their interest drift in real time,and can better solve the classical key issues faced by traditional recommender systems.Nowadays,reinforcement lear-ning has become a hot research topic in the field of recommendation systems.From the perspective of survey,this paper first analyzes the improvement ideas of reinforcement learning for recommender systems based on a brief review of recommender systems and reinforcement learning.Then,the paper makes a general overview and summary of reinforcement learning based recommender systems in recent years,and further summarizes the research situation of traditional reinforcement learning based recommendation and deep reinforcement learning based recommendation respectively.Furthermore,the paper summarizes the frontiers of reinforcement learning based recommendation research topic in recent years and its application.Finally,the future development trend and application of reinforcement learning in recommender systems are analyzed.

Objective To evaluate the feasibility, safety, and short-term outcomes of middle rectal resection followed by transanal specimen extraction. Methods Forty-four patients with small mid-rectal tumors underwent laparoscopic rectal resection followed by transanal specimen extraction. Results The procedure was successful in all patients without intraoperative conversion or additional access. The mean operation time was 182.7 minutes (range, 130–255 minutes), the mean blood loss was 26.5 mL (range, 5–120 mL), the mean postoperative exhaust time was 31.3 hours (range, 16–60 hours), and the mean length of hospital stay was 9.5 days (range, 8–19 days). One patient developed anastomotic leakage, which was treated by intravenous antibiotics and daily pelvic cavity flushes through the abdominal drainage tube. No infection-related complications or anal incontinence were observed. The mean tumor size was 2.1 cm (range, 1.6–3.2 cm), the mean number of harvested lymph nodes was 16.5 (range, 6–31), and the mean follow-up time was 8.5 months (range, 2–16 months). By the last follow-up, no signs of recurrence had been found in any patient. Conclusion The combination of standard laparoscopic proctectomy and transanal specimen extraction could become a well-established strategy for selected patients.

Acute kidney injury (AKI) is a common clinical syndrome with complex pathogenesis, characterized by a rapid decline in kidney function in the short term. Worse still, the incomplete recovery from AKI increases the risk of progression to chronic kidney disease (CKD). However, the pathogenesis and underlying mechanism remain largely unknown. Macrophages play an important role during kidney injury and tissue repair, but its role in AKI-to-CKD transition remains elusive. Herein, single nucleus RNA sequencing (snRNA-Seq) and flow cytometry validations showed that E-type prostaglandin receptor 4 (EP4) was selectively activated in renal macrophages, rather than proximal tubules, in ischemia-reperfusion injury (IRI)-induced AKI-to-CKD transition mouse model. EP4 inhibition aggravated AKI-to-CKD transition, while EP4 activation impeded the progression of AKI to CKD though regulating macrophage polarization. Mechanistically, network pharmacological analysis and subsequent experimental verifications revealed that the activated EP4 inhibited macrophage polarization through inducing Carnitine palmitoyltransferase 2 (CPT2)-mediated lipophagy in macrophages. Further, CPT2 inhibition abrogated the protective effect of EP4 on AKI-to-CKD transition. Taken together, our findings demonstrate that EP4-CPT2 signaling-mediated lipophagy in macrophages plays a pivotal role in the transition of AKI to CKD and targeting EP4-CPT2 axis could serve as a promising therapeutic approach for retarding AKI and its progression to CKD.

Cardiorenal syndrome (CRS) is defined as a disorder of the heart and kidney, in which acute or chronic injury of one organ may lead to acute or chronic dysfunction of the other. It is characterized by high morbidity and mortality, resulting in high economic costs and social burdens. However, there is currently no effective drug-based treatment. Emerging evidence implicates the involvement of mitophagy in the progression of CRS, including cardiovascular disease (CVD) and chronic kidney disease (CKD). In this review, we summarized the crucial roles and molecular mechanisms of mitophagy in the pathophysiology of CRS. It has been reported that mitophagy impairment contributes to a vicious loop between CKD and CVD, which ultimately accelerates the progression of CRS. Further, recent studies revealed that targeting mitophagy may serve as a promising therapeutic approach for CRS, including clinical drugs, stem cells and small molecule agents. Therefore, studies focusing on mitophagy may benefit for expanding innovative basic research, clinical trials, and therapeutic strategies for CRS.

BackgroundRadiation therapy (RT) is a standard treatment for the local control of primary pelvic cancers (PPC), yet the risk of second corpus uteri cancer (SCUC) in PPC patients undergoing RT is still controversial. This study investigated the impact of RT on the risk of SCUC and assessed the survival outcome.MethodsWe queried nine cancer registries for PPC cases in the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence of SCUC was analyzed using Cox regression and Fine–Gray competing risk regression analysis. The Poisson regression analysis was employed to assess the standardized incidence ratios (SIRs) and radiation-attributed risk (RR) for SCUC. We evaluated the overall survival of patients with SCUC using the Kaplan–Meier method.ResultsReceiving radiotherapy was strongly associated with a higher risk of developing SCUC for PPC patients in Fine–Gray competing risk regression (No-RT vs. RT: adjusted HR = 1.77; 95% CI, 1.40–2.28; p < 0.001). The incidence of SCUC in PPC patients who received RT was higher than in the US general population (SIR, 1.66; 95% CI, 1.41–1.93; p < 0.05), but the incidence of SCUC in patients who did not receive RT was lower than with the US general population (SIR, 0.68; 95% CI, 0.61–0.75; p < 0.05). The dynamic SIR and RR for SCUC decreased with decreasing age at PPC diagnosis and decreased with time progress. In terms of overall survival, 10-year survival rates with SCUC after No-RT (NRT) and SCUC after RT were 45.9% and 25.9% (HR = 1.82; 95% CI, 1.46–2.29; p < 0.001), respectively.ConclusionRadiotherapy for primary pelvic cancers is associated with a higher risk of developing SCUC than patients unexposed to radiotherapy. We suggest that patients with pelvic RT, especially young patients, should receive long-term monitoring for the risk of developing SCUC.

Background: The type 2 mannose receptor C (MRC2) is involved in tumor biological processes and plays a new role in the remodeling of the extracellular matrix turnover. Previous studies have demonstrated MRC2 expression profiling and prognostic relevance in some tumor types. However, the clinical and immunotherapeutic value of MRC2 in pan-cancers remains controversial. Our study aimed to evaluate MRC2 expression pattern, clinical characteristics and prognostic significance in 33 cancers, explore the relationship between MRC2 and immune-related characteristics, and assess the prediction of MRC2 for the immunotherapeutic response.Methods: Transcriptional and clinical data of 33 cancers were downloaded from The Cancer Genome Atlas database (TCGA) database and two independent immunotherapeutic cohorts were obtained from GSE67501 and the IMvigor210 study. Next, patients stratified by MRC2 expression levels were displayed by Kaplan-Meier plot to compare prognosis-related indexes. Meanwhile, immune infiltrates of different cancers were estimated by tumor immune estimation resources (TIMER) and CIBERSORT. The ESTIMATE algorithm was used to estimate the immune and stromal scores in tumor tissues. MRC2 expression and immunological modulators, including immune inhibitors, immune stimulators, and MHC molecules, were screened through the TISIDB portal. Gene-set enrichment analysis analyses were performed to explore the underlying biological process of MRC2 across different cancers. The immunotherapeutic response prediction was performed in two independent cohorts (GSE78220: metastatic melanoma with pembrolizumab treatment and IMvigor210: advanced urothelial cancer with atezolizumab intervention).Results: MRC2 is expressed differently in many cancers and has been shown to have potential prognostic predicting significance. MRC2 was significantly associated with immune cell infiltration, immune modulators, and immunotherapeutic markers. Notably, the immunotherapeutic response group was associated with lower MRC2 expression in metastatic melanoma and advanced urothelial carcinoma cohort.Conclusion: This study demonstrated that MRC2 could be a prognostic indicator for certain cancer and is critical for tumor immune microenvironments. MRC2 expression level may influence and predict immune checkpoint blockade response as a potential indicator.

BackgroundRadiation therapy (RT) is a crucial modality for the local control of pelvic cancer (PC), but the effect of pelvic RT on the development of secondary malignancy is still unclear. This study aimed to identify the relationship between radiation therapy received for the treatment of primary PC and subsequent secondary bladder cancer (SBC).MethodsThe Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for PC. Fine-gray competing risk regression and Cox regression analyses were employed to assess the cumulative incidence of SBC. Poisson regression and multiple primary standardized incidence ratios (SIR) were used to evaluate the radiotherapy-associated risk for patients receiving RT. Subgroup analyses of patients stratified by latency time since PC diagnosis, calendar year of PC diagnosis stage, and age at PC diagnosis were also performed. Overall survival (OS) was compared among different treatment groups with SBC by Kaplan–Meier analysis.ResultsA total of 318,165 observations showed that the primary cancers were located in pelvic cavity, 256,313 patients did not receive radiation therapy (NRT), 51,347 patients who underwent external beam radiation therapy (EBRT), and 10,505 patients receiving a combination of EBRT and brachytherapy (EBRT–BRT) who developed SBC. Receiving two types of radiotherapy was strongly consistent with a higher risk of developing SBC for PC patients in Fine-Gray competing risk regression (NRT vs. EBRT, adjusted HR= 1.71, 95% CI: 1.54-1.90, P

Background: Acute kidney injury (AKI) occurs in approximately 7–18% of all hospitalizations, but there are currently no effective drug therapy for preventing AKI or delaying its progression to chronic kidney disease (CKD). Recent studies have shown that Scutellaria baicalensis, a traditional Chinese herb, could attenuate cisplatin-induced AKI, although the mechanism remains elusive. Further, it is unknown whether its major active component, Oroxylin A (OA), can alleviate kidney injury.Methods: The therapeutic effect of OA was evaluated by using ischemia-reperfusion (IR) and cisplatin mediated-AKI mice and HK-2 cells under hypoxia-reoxygenation (HR) conditions. HE staining, transmission electron microscopy, flow cytometry, immunofluorescence, qPCR, Western blot, PPARα inhibitor, BNIP3 siRNA and ChIP assay were used to explore the role and mechanism of OA in AKI.Results: OA ameliorated tubular damage and dramatically decreased serum creatinine (Scr) and urea nitrogen (BUN), and the expressions of renal injury markers (Kim-1, Ngal) in AKI mice induced by both IR injury and cisplatin, as well as attenuating AKI-to-CKD transition. In vitro experiments showed that OA alleviated HR-induced mitochondrial homeostasis imbalance in renal tubular epithelial cells. Mechanistically, OA dose-dependently induced the expression of Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3), while knockdown of BNIP3 expression reversed the protection of OA against HR-mediated mitochondrial injury. Network pharmacological analysis and experimental validation suggested that OA enhanced BNIP3 expression via upregulating the expression of peroxisome proliferator activated receptor alpha (PPARα), which induced the transcription of BNIP3 via directly binding to its promoter region. Both in vitro and in vivo experiments confirmed that the renoprotective effect of OA was dramatically reduced by GW6471, a PPARα antagonist.Conclusion: Our findings revealed that OA ameliorates AKI-to-CKD transition by maintaining mitochondrial homeostasis through inducing PPARα-BNIP3 signaling pathway, indicating that OA may serve as a candidate therapeutic strategy for alleviating AKI and CKD.

Background This study aimed to investigate the association between radiotherapy for cancer and cardiovascular disease (CVD) deaths and evaluate the relative risk for CVD deaths in the general population and among patients with cancer treated with radiotherapy. Methods and Results The statistics of cancers from 16 sites were extracted from the Surveillance, Epidemiology, and End Results database and evaluated. Multivariable Cox proportional hazards regression analysis was used to analyze the association between radiotherapy and cardiovascular‐specific survival. The standardized mortality ratio for CVD deaths was estimated by comparing the observed deaths of patients with cancer treated with radiotherapy to the expected deaths of the general population. Of the 2 214 944 patients identified from the database, 292 102 (13.19%) died from CVD. Multivariable Cox proportional hazards regression analyses demonstrated that radiotherapy was an independent risk factor for cardiovascular‐specific survival among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. The long‐term cardiovascular‐specific survival of patients with cancer who underwent radiotherapy was significantly lower than that of patients who did not undergo radiotherapy. The incidence of CVD deaths among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers who underwent radiotherapy was higher than that among the general population. Standardized mortality ratio significantly decreased with increasing age at cancer diagnosis, gradually decreased within 10 years of diagnosis and increased after 10 years of diagnosis. Conclusions Radiotherapy is associated with worse cardiovascular‐specific survival in patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. Long‐term surveillance of cardiovascular conditions should be performed after radiotherapy.