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Abstract Background Sustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking. Methods We adopted cross-species, single-cell RNA sequencing (scRNA-seq) analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9 −/− mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage. Results ScRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis, for which distinct monocyte subsets were enriched in disparate subclusters of septic patients. We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR (HLA-DR), which were prominently enriched in septic patients and might exert immunosuppressive function. By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments, we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice, corresponding to HLA-DR low S100A high monocytes in human sepsis. Moreover, we found that S100A9+ monocytes exhibited profound immunosuppressive function on CD4+ T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression. Conclusions This study identifies HLA-DR low S100A high monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.

Cannabidiol (CBD) is a terpenoid naturally found in plants. The purified compound is used in the treatment of mental disorders because of its antidepressive, anxiolytic, and antiepileptic effects. CBD can affect the regulation of several pathophysiologic processes, including autophagy, cytokine secretion, apoptosis, and innate and adaptive immune responses. However, several authors have reported contradictory findings concerning the magnitude and direction of CBD-mediated effects. For example, CBD treatment can increase, decrease, or have no significant effect on autophagy and apoptosis. These variable results can be attributed to the differences in the biological models, cell types, and CBD concentration used in these studies. This review focuses on the mechanism of regulation of autophagy and apoptosis in inflammatory response and cancer by CBD. Further, we broadly elaborated on the prospects of using CBD as an anti-inflammatory agent and in cancer therapy in the future.

Early gastric cancer (EGC) has a desirable prognosis compared with advanced gastric cancer (AGC). The surgical concept of EGC has altered from simply emphasizing radical resection to both radical resection and functional preservation. As the mainstream surgical methods for EGC, both endoscopic resection and laparoscopic resection have certain inherent limitations, while the advent of laparoscopic and endoscopic cooperative surgery (LECS) has overcome these limitations to a considerable extent. LECS not only expands the surgical indications for endoscopic resection, but greatly improves the quality of life (QOL) in EGC patients. This minireview elaborates on the research status of LECS for EGC, from the conception and development of LECS, to the tentative application of LECS in animal experiments, then to case reports and retrospective clinical studies. Finally, the challenges and prospects of LECS in the field of EGC are prospected and expounded, hoping to provide some references for relevant researchers. With the in-depth understanding of minimally invasive technology, LECS remains a promising option in the management of EGC. Carrying out more related multicenter prospective clinical researches is the top priority of promoting the development of this field in the future.

BackgroundSepsis is considered an intractable dysfunction that results from the disordered host immune response to uncontrolled infection. Even though the precise mechanism of sepsis remains unclear, scientific advances have highlighted the key role of various programmed cell death processes in the pathophysiology of sepsis. The current study aims to explore the worldwide research trend on programmed cell death in the setting of sepsis and assesses the achievements of publications from various countries, institutions, journals, and authors globally.Material and methodsAssociated publications during 2002–2022 with the topical subject of sepsis and programmed cell death were extracted from the Web of Science. VOSviewer was utilized to evaluate and map the published trend in the relevant fields.ResultsAll 2,037 relevant manuscripts with a total citation of 71,575 times were screened out by the end of 1 January 2022. China accounted for the largest number of publications (45.07%) and was accompanied by corporate citations (11,037) and H-index (48), which ranked second globally. The United States has been ranked first place with the highest citations (30,775) and H-index (88), despite a low publication number (29.95%), which was subsequent to China. The journal Shock accounted for the largest number of publications in this area. R. S. Hotchkiss, affiliated with Washington University, was considered to have published the most papers in the relevant fields (57) and achieved the highest citation frequencies (9,523). The primary keywords on the topic of programmed cell death in sepsis remarkably focused on “inflammation” “immunosuppression”, and “oxidative stress”, which were recognized as the core mechanisms of sepsis, eventually attributing to programmed cell death. The involved research on programmed cell death induced by immune dysregulation of sepsis was undoubtedly the hotspot in the pertinent areas.ConclusionsThe United States has been academically outstanding in sepsis-related research. There appears to be an incompatible performance between publications and quantity with China. Frontier advances may be consulted in the journal Shock. The leading-edge research on the scope of programmed cell death in sepsis should preferably focus on immune dissonance-related studies in the future.

IntroductionAs the first bibliometric analysis of COVID-19 and immune responses, this study will provide a comprehensive overview of the latest research advances. We attempt to summarize the scientific productivity and cooperation across countries and institutions using the bibliometric methodology. Meanwhile, using clustering analysis of keywords, we revealed the evolution of research hotspots and predicted future research focuses, thereby providing valuable information for the follow-up studies.MethodsWe selected publications on COVID-19 and immune response using our pre-designed search strategy. Web of Science was applied to screen the eligible publications for subsequent bibliometric analyses. GraphPad Prism 8.0, VOSviewer, and CiteSpace were applied to analyze the research trends and compared the contributions of countries, authors, institutions, and journals to the global publications in this field.ResultsWe identified 2,200 publications on COVID-19 and immune response published between December 1, 2019, and April 25, 2022, with a total of 3,154 citations. The United States (611), China (353), and Germany (209) ranked the top three in terms of the number of publications, accounting for 53.3% of the total articles. Among the top 15 institutions publishing articles in this area, four were from France, four were from the United States, and three were from China. The journal Frontiers in Immunology published the most articles (178) related to COVID-19 and immune response. Alessandro Sette (31 publications) from the United States were the most productive and influential scholar in this field, whose publications with the most citation frequency (3,633). Furthermore, the development and evaluation of vaccines might become a hotspot in relevant scope.ConclusionsThe United States makes the most indispensable contribution in this field in terms of publication numbers, total citations, and H-index. Although publications from China also take the lead regarding quality and quantity, their international cooperation and preclinical research need to be further strengthened. Regarding the citation frequency and the total number of published articles, the latest research progress might be tracked in the top-ranking journals in this field. By analyzing the chronological order of the appearance of retrieved keywords, we speculated that vaccine-related research might be the novel focus in this field.

BackgroundChemotherapy, radiotherapy, targeted therapy and immunotherapy have demonstrated expected clinical efficacy, while drug resistance remains the predominant limiting factor to therapeutic failure in patients with colorectal cancer (CRC). Although there have been numerous basic and clinical studies on CRC resistance in recent years, few publications utilized the bibliometric method to evaluate this field. The objective of current study was to provide a comprehensive analysis of the current state and changing trends of drug resistance in CRC over the past 20 years.MethodsThe Web of Science Core Collection (WOSCC) was utilized to extracted all studies regarding drug resistance in CRC during 2002-2021. CiteSpace and online platform of bibliometrics were used to evaluate the contributions of various countries/regions, institutions, authors and journals in this field. Moreover, the recent research hotspots and promising future trends were identified through keywords analysis by CiteSpace and VOSviewer.Results1451 related publications from 2002 to 2021 in total were identified and collected. The number of global publications in this field has increased annually. China and the USA occupied the top two places with respect to the number of publications, contributing more than 60% of global publications. Sun Yat-sen University and Oncotarget were the institution and journal which published the most papers, respectively. Bardelli A from Italy was the most prolific writer and had the highest H-index. Keywords burst analysis identified that “Growth factor receptor”, “induced apoptosis” and “panitumumab” were the ones with higher burst strength in the early stage of this field. Analysis of keyword emergence time showed that “oxaliplatin resistance”, “MicroRNA” and “epithelial mesenchymal transition (EMT)” were the keywords with later average appearing year (AAY).ConclusionsThe number of publications and research interest on drug resistance in CRC have been increasing annually. The USA and China were the main driver and professor Bardelli A was the most outstanding researcher in this field. Previous studies have mainly concentrated on growth factor receptor and induced apoptosis. Oxaliplatin resistance, microRNA and EMT as recently appeared frontiers of research that should be closely tracked in the future.

Peptic ulcer (PU) is a common and frequently occurring disease. Although PU seriously threatens the lives and health of global residents, the applications of artificial intelligence (AI) have strongly promoted diversification and modernization in the diagnosis and treatment of PU. This minireview elaborates on the research progress of AI in the field of PU, from PU’s pathogenic factor Helicobacter pylori (Hp) infection, diagnosis and differential diagnosis, to its management and complications (bleeding, obstruction, perforation and canceration). Finally, the challenges and prospects of AI application in PU are prospected and expounded. With the in-depth understanding of modern medical technology, AI remains a promising option in the management of PU patients and plays a more indispensable role. How to realize the robustness, versatility and diversity of multifunctional AI systems in PU and conduct multicenter prospective clinical research as soon as possible are the top priorities in the future.

During winter wheat production, aphids need to be controlled with pesticides for the entire growth period. Controlled-release technology has been regarded as an alternative method for the improvement of pesticide efficiency. This study investigated two types of imidacloprid controlled-release granule (CR-GR): 2% imidacloprid CR-GR and 0.2% imidacloprid pesticide-fertilizer controlled-release granule (PF-CR-GR) when wheat was sown in winter. The release performance, utilization rate, terminal residues in edible parts, control effect on aphids, and achieved winter wheat yield were evaluated for both laboratory experiments and field application. Imidacloprid PF-CR-GR released more quickly in aqueous medium than CR-GR because of its good water solubility. After CR-GR treatments, the concentrations in wheat roots and soil were similar throughout the entire sampling period, and the concentrations in shoots were about 10–20% of those in roots. Imidacloprid was better absorbed when CR-GR was used as root treatment, compared with foliar treatment. Field application showed that imidacloprid CR-GR and PF-CR-GR controlled aphids throughout the entire growth period of winter wheat and improved the wheat yield. These findings identified application of imidacloprid CR-GR and PF-CR-GR on winter wheat as an effective way to enhance the pesticide utilization rate and ensure adequate yield. This paper provides a theoretical basis for the scientific use of pesticides and guides scientific pesticide application.

BackgroundMultiple Organ Dysfunction Syndrome (MODS) is a major cause of high morbidity and mortality among patients in intensive care units (ICU). Although numerous basic and clinical researches on MODS have been conducted, there is still a long way to go to prevent patients from entering this stage. To our knowledge, no bibliometric analyses of MODS have been reported, this study, therefore, was conducted to reveal MODS research status and trends during 2001–2021.MethodsAll relevant literature covering MODS during 2001–2021 were extracted from Web of Science. An online analysis platform of literature metrology was used to analyze the publication trends. VOSviewer software was used to collect and analyze the keywords and research hotspots related to MODS.ResultsAs of July 31, 2021, a total of 994 MODS-related articles from 2001 to 2021 were identified. The United States accounted for the largest number of publications (31.1%), followed by China and Germany, with 186 and 75 publications, respectively. Among all the institutions, the University of Pittsburgh published the most papers related to MODS (21). Critical Care Medicine published the most papers in this field (106). Professor Moore EE, who had the most citation frequency (1847), made great achievements in MODS research. Moreover, analysis of the keywords identified three MODS research hotspot clusters: “mechanism-related research,” “clinical research,” and “diagnostic research.”ConclusionsThe United States maintained a top position worldwide and made the most outstanding contribution in the MODS field. In terms of publication, China was next only to the United States, but there was a disproportion between the quantity of publications and citation frequency. The institution University of Pittsburgh and journal Critical Care Medicine represent the highest level of research in this field. During the 20 years from 2001 to 2021, basic MODS research has been in-depth yet progressed relatively slowly recently, but the outbreak of COVID-19 has to some extent set off an upsurge of clinical research in MODS field.

Abstract Background The coronavirus disease 2019 (COVID-19) has been declared a global pandemic by the World Health Organization. Patients with cancer are more likely to incur poor clinical outcomes. Due to the prevailing pandemic, we propose some surgical strategies for gastric cancer patients. Methods The ‘COVID-19’ period was defined as occurring between 2020 and 01-20 and 2020-03-20. The enrolled patients were divided into two groups, pre-COVID-19 group (PCG) and COVID-19 group (CG). A total of 109 patients with gastric cancer were enrolled in this study. Results The waiting time before admission increased by 4 days in the CG (PCG: 4.5 [IQR: 2, 7.8] vs. CG: 8.0 [IQR: 2,20]; p = 0.006). More patients had performed chest CT scans besides abdominal CT before admission during the COVID-19 period (PCG: 22 [32%] vs. CG: 30 [73%], p = 0.001). After admission during the COVID period, the waiting time before surgery was longer (PCG: 3[IQR: 2,5] vs. CG: 7[IQR: 5,9]; p

BackgroundThe incidence of coagulopathy, which was responsible for poor outcomes, was commonly seen among patients with sepsis. In the current study, we aim to determine whether the presence of sepsis-associated coagulopathy (SAC) predicts the clinical outcomes among critically ill patients with postoperative sepsis.MethodsWe conducted a single-center retrospective cohort study by including patients with sepsis admitted to surgical ICU of Chinese PLA General Hospital from January 1, 2014 to December 31, 2018. Baseline characteristics and clinical outcomes were compared with respect to the presence of SAC. Kaplan-Meier analysis was applied to calculate survival rate, and Log-rank test was carried out to compare the differences between two groups. Furthermore, multivariable Cox and logistic and linear regression analysis were performed to assess the relationship between SAC and clinical outcomes, including hospital mortality, development of septic shock, and length of hospital stay (LOS), respectively. Additionally, both sensitivity and subgroup analyses were performed to further testify the robustness of our findings.ResultsA total of 175 patients were included in the current study. Among all included patients, 41.1% (72/175) ICU patients were identified as having SAC. In-hospital mortality rates were significantly higher in the SAC group when compared to that of the No SAC group (37.5% vs. 11.7%; p < 0.001). By performing univariable and multivariable regression analyses, presence of SAC was demonstrated to significantly correlate with an increased in-hospital mortality for patients with sepsis in surgical ICU [Hazard ratio (HR), 3.75; 95% Confidence interval (CI), 1.90–7.40; p < 0.001]. Meanwhile, a complication of SAC was found to be the independent predictor of the development of septic shock [Odds ratio (OR), 4.11; 95% CI, 1.81–9.32; p = 0.001], whereas it was not significantly associated with prolonged hospital LOS (OR, 0.97; 95% CI, 0.83–1.14; p = 0.743).ConclusionThe presence of SAC was significantly associated with increased risk of in-hospital death and septic shock among postoperative patients with sepsis admitted to ICU. Moreover, there was no statistical difference of hospital LOS between the SAC and no SAC groups.

Background: Autophagy plays a pivotal role in the progression and management of colorectal cancer (CRC). Recently, numerous articles focusing on the role of autophagy in CRC have emerged. The present study was conducted to provide a comprehensive analysis of the current state and changing trends in the relationship of autophagy and CRC over the past 20 years. Methods: The Web of Science Core Collection (WOSCC) was utilized to extracted all publications with respect to autophagy and CRC during 2002–2021. The contributions of various countries/regions, institutions and journals in this field were analyzed, moreover, research hotspots and promising future trends predicted through keywords were identified by the online platform of bibliometrics, CiteSpace and VOSviewer. Results: A total of 2418 related publications from 2002 to 2021 were identified and collected. China occupied first place with respect to the number of publications, followed by the USA and South Korea. Shanghai Jiao Tong University published the most papers in this field. Most publications were published in Oncotarget. Additionally, analysis of the keywords identified 4 clusters with various research focuses: “mechanism-related research”, “clinical-related research”, “tumorigenesis research” and “chemotherapy-related research”. The three latest hot keywords in this field were epithelial–mesenchymal transition (EMT), promote and invasion. Conclusions: The number of publications and research interest on autophagy and CRC are increasing annually, and the USA had prominent academic positions in the field. Shanghai Jiao Tong University represents a high level of research and the latest progress in this field can be tracked at Oncotarget. Throughout the research history of autophagy and CRC in the past 20 years, previous studies have mainly concentrated on apoptosis and drug resistance in tumor cells, while EMT in regulating tumorigenesis and development of clinical drugs that inhibit tumor invasion through autophagy may be novel hotspots in the future.

Transcription factor EB (TFEB) is a member of the microphthalmia-associated transcription factor/transcription factor E (MiTF/TFE) family and critically involved in the maintenance of structural integrity and functional balance of multiple cells. In this review, we described the effects of post-transcriptional modifications, including phosphorylation, acetylation, SUMOylation, and ubiquitination, on the subcellular localization and activation of TFEB. The activated TFEB enters into the nucleus and induces the expressions of targeted genes. We then presented the role of TFEB in the biosynthesis of multiple organelles, completion of lysosome-autophagy pathway, metabolism regulation, immune, and inflammatory responses. This review compiles existing knowledge in the understanding of TFEB regulation and function, covering its essential role in response to cellular stress. We further elaborated the involvement of TFEB dysregulation in the pathophysiological process of various diseases, such as the catabolic hyperactivity in tumors, the accumulation of abnormal aggregates in neurodegenerative diseases, and the aberrant host responses in inflammatory diseases. In this review, multiple drugs have also been introduced, which enable regulating the translocation and activation of TFEB, showing beneficial effects in mitigating various disease models. Therefore, TFEB might serve as a potential therapeutic target for human diseases. The limitation of this review is that the mechanism of TFEB-related human diseases mainly focuses on its association with lysosome and autophagy, which needs deep description of other mechanism in diseases progression after getting more advanced information.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective measure for improving the prognosis of colorectal cancer (CRC) patients with peritoneal carcinomatosis (PC). However, the role of HIPEC in CRC patients at high risk of PC remains controversial. The current systematic review and meta-analysis aimed to evaluate the clinical efficacy and safety of HIPEC in CRC patients at high risk of PC.Methods: We performed a systematic search of PubMed, Embase, Cochrane Library, and other online databases up to July 30, 2020. The clinical data, including overall survival, disease free survival, peritoneal metastasis rate, and postoperative adverse reaction were screened and analyzed after data extraction. Risk ratios (RRs) were applied to analyze these dichotomous outcomes with a random effects model.Results: A total of 6 available clinical studies involving 603 patients were finally included. CRC patients at high risk of PC who proactively underwent HIPEC treatment showed a significantly reduced peritoneal metastasis rate (RR: 0.41, 95% CI: 0.21–0.83, P = 0.01; I2 = 58%) compared to the similarly high-risk in CRC patients who did not receive HIPEC treatment. However, in terms of overall survival (RR: 1.13, 95% CI: 0.97–1.33, P = 0.12; I2 = 77%), disease-free survival (RR: 1.10, 95% CI: 0.75–1.59, P = 0.63; I2 = 53%), progression free survival (RR: 1.85, 95% CI: 0.48–7.14, P = 0.37; I2 = 93%), and postoperative adverse reactions (RR: 0.1.07, 95% CI: 0.36–3.15, P = 0.90; I2 = 78%), there was no significant difference between the HIPEC treatment and control groups.Conclusions: Proactive HIPEC treatment did not show the expected clinical efficacy in prolonging the overall survival time, disease-free survival time, and progression-free survival time of CRC patients at high risk of PC. However, the preemptive administration of HIPEC was associated with a reduced peritoneal metastasis rate and did not cause adverse additional postoperative effects.

Introduction: The incidence of postoperative sepsis is continually increased, while few studies have specifically focused on the risk factors and clinical outcomes associated with the development of sepsis after surgical procedures. The present study aimed to develop a mathematical model for predicting the in-hospital mortality among patients with postoperative sepsis.Materials and Methods: Surgical patients in Medical Information Mart for Intensive Care (MIMIC-III) database who simultaneously fulfilled Sepsis 3.0 and Agency for Healthcare Research and Quality (AHRQ) criteria at ICU admission were incorporated. We employed both extreme gradient boosting (XGBoost) and stepwise logistic regression model to predict the in-hospital mortality among patients with postoperative sepsis. Consequently, the model performance was assessed from the angles of discrimination and calibration.Results: We included 3,713 patients who fulfilled our inclusion criteria, in which 397 (10.7%) patients died during hospitalization, and 3,316 (89.3%) patients survived through discharge. Fluid-electrolyte disturbance, coagulopathy, renal replacement therapy (RRT), urine output, and cardiovascular surgery were important features related to the in-hospital mortality. The XGBoost model had a better performance in both discriminatory ability (c-statistics, 0.835 vs. 0.737 and 0.621, respectively; AUPRC, 0.418 vs. 0.280 and 0.237, respectively) and goodness of fit (visualized by calibration curve) compared to the stepwise logistic regression model and baseline model.Conclusion: XGBoost model has a better performance in predicting hospital mortality among patients with postoperative sepsis in comparison to the stepwise logistic regression model. Machine learning-based algorithm might have significant application in the development of early warning system for septic patients following major operations.