First identification and isolation of equine herpesvirus type 1 in aborted fetal lung tissues of donkeys.

BACKGROUND: Equine herpesvirus type 1 (EHV-1) is commonly associated with horse abortion. Currently, there are no reported cases of abortion resulting from EHV-1 infection in donkeys. RESULTS: This was the first survey-based study of Chinese donkeys. The presence of EHV-1 was identified by PCR. This survey was conducted in Chabuchar County, North Xinjiang, China, in 2020. A donkey EHV-1 strain (Chabuchar/2020) was successfully isolated in MDBK cells. Seventy-two of 100 donkey sera were able to neutralize the isolated EHV-1. Moreover, the ORF33 sequence of the donkey-origin EHV-1 Chabuchar/2020 strain showed high levels of similarity in both its nucleotide (99.7‒100%) and amino acid (99.5‒100%) sequences, with those of horse EHV-1 strains. EHV-1 Chabuchar/2020 showed significant consistency and was classified within cluster 1 of horse EHV-1 strains. Further, analysis of the expected ORF30 nucleotide sequence revealed that donkey EHV-1 strains contained guanine at position 2254, resulting in a change to aspartic acid at position 752 of the viral DNA polymerase. Therefore, these strains were classified as horse neuropathogenic strains. Lastly, a phylogenetic tree was constructed using the partial ORF68 nucleotide sequences, showing that the identified donkey EHV-1 strain and the EHV-1 strain found in aborted Yili horses in China comprised a novel independent VIII group. CONCLUSION: This study showed the first isolation and identification of EHV-1 as an etiological agent of abortions in donkeys. Further analysis of the ORF33, ORF30, and ORF68 sequences indicated that the donkey EHV-1 contained the neuropathogenic genotype of strains in the VIII group. It is thus important to be aware of EHV-1 infection in the donkey population, even though the virus has only been identified in donkey abortions in China.

Identification of neuropathogenic Varicellovirus equidalpha1 as a potential cause of respiratory disease outbreaks among horses in North Xinjiang, China, from 2021-2023.

BACKGROUND: Varicellovirus equidalpha1 (formerly Equid alphaherpesvirus 1, EqAHV-1) is among the most important viruses responsible for respiratory disease outbreaks among horses throughout the world. No reports to date have detailed the association between EqAHV-1 and respiratory disease among horses in China. This study described one such outbreak among a population of horses in north Xinjiang that occurred from April 2021 - May 2023. RESULTS: qPCR revealed that EqAHV-1 was detectable in all samples and this virus was identified as a possible source of respiratory disease, although a limited subset of these samples were also positive for EqAHV-2, EqAHV-4, and EqAHV-5. In total, three EqAHV-1 strains responsible for causing respiratory illness in horses were isolated successfully, and full-length ORF33 sequence comparisonsand phylogenetic analyses indicated that these isolates may have originated from EqAHV-1 strains detected in Yili horse abortions. ORF30 sequence data additionally suggested that these strains were neuropathic, as evidenced by the presence of a guanine residue at nucleotide position 2254 corresponding to the aspartic acid present at position 752 in the DNA polymerase encoded by this virus. CONCLUSION: This study is the first report of an outbreak of respiratory disease among horses in China caused by EqAHV-1. ORF30 sequence characterization revealed that these EqAHV-1 strains harbored a neuropathogenic genotype. Given the detection of this virus in horses suffering from respiratory disease, concern is warranted with respect to this neuropathogenic EqAHV-1 outbreak.

Cloud 3D-QSAR: a web tool for the development of quantitative structure-activity relationship models in drug discovery.

Effective drug discovery contributes to the treatment of numerous diseases but is limited by high costs and long cycles. The Quantitative Structure-Activity Relationship (QSAR) method was introduced to evaluate the activity of a large number of compounds virtually, reducing the time and labor costs required for chemical synthesis and experimental determination. Hence, this method increases the efficiency of drug discovery. To meet the needs of researchers to utilize this technology, numerous QSAR-related web servers, such as Web-4D-QSAR and DPubChem, have been developed in recent years. However, none of the servers mentioned above can perform a complete QSAR modeling and supply activity prediction functions. We introduce Cloud 3D-QSAR by integrating the functions of molecular structure generation, alignment, molecular interaction field (MIF) computing and results analysis to provide a one-stop solution. We rigidly validated this server, and the activity prediction correlation was R2 = 0.934 in 834 test molecules. The sensitivity, specificity and accuracy were 86.9%, 94.5% and 91.5%, respectively, with AUC = 0.981, AUCPR = 0.971. The Cloud 3D-QSAR server may facilitate the development of good QSAR models in drug discovery. Our server is free and now available at http://chemyang.ccnu.edu.cn/ccb/server/cloud3dQSAR/ and http://agroda.gzu.edu.cn:9999/ccb/server/cloud3dQSAR/.

Evidence for the Metabolic Activation of Deferasirox In Vitro and In Vivo.

Deferasirox (DFS) is used for the treatment of iron accumulation caused by the need for long-term blood transfusions, such as thalassemia or other rare anemia. Liver injury due to exposure to DFS has been documented, and the toxic mechanisms of DFS are unknown. The present study aimed to investigate the reactive metabolites of DFS in vitro and in vivo to help us understand the mechanisms of DFS hepatotoxicity. Two hydroxylated metabolites (5-OH and 5'-OH) were identified during incubation of DFS-supplemented rat liver microsomes. Such microsomal incubations fortified with glutathione (GSH) or N-acetylcysteine (NAC) as capture agents offered two GSH conjugates and two NAC conjugates. These GSH conjugates and NAC conjugates were also detected in bile and urine of rats given DFS. CYP1A2 and CYP3A4 were found to dominate the metabolic activation of DFS. Administration of DFS induced decreased cell survival in cultured primary hepatocytes. Pretreatment with ketoconazole and 1-aminobenzotrizole made hepatocytes less susceptible to the cytotoxicity of DFS.

Abortion storm of Yili horses is associated with Equus caballus papillomavirus 2 variant infection.

Nine different species of Equus caballus papillomavirus (EcPV) and three bovine papillomaviruses (BPVs) have been reported to infect horses. However, there are few descriptions of such infections in China. In our pioneer study on Chinese horses, we identified EcPV-2 in the nasal swabs (4/230, 1.7%) of Yili horses, and the semen (3/18, 16.7%) of thoroughbred horses. This indicated that EcPV is indeed hosted by horses in China, and that EcPV-2 might be transmitted though breeding. Further detection of EcPVs in the lung tissues of aborted fetuses of Yili horses, which were originally negative for equid herpes viruses, demonstrated EcPV-2 positivity in 19 of 50 samples, thereby indicating that EcPV-2 may be a new pathogen responsible for causing abortion. Thereafter, sequence analyses of the L1 genes of 26 EcPV-2 in China were performed, indicating that EcPV-2, which primarily infects horses in China, shared 98.3-99.9% nt identity with the published sequences for EcPV-2. These observations indicated that EcPV-2 identified in the current study were highly similar variants of the previously identified strains of EcPV-2. Phylogenetic analysis based on L1 gene sequences from GenBank showed that the EcPV-2 found in Chinese horses was closely related to and clustered together with an already known EcPV-2a lineage. Our study provides the first evidence related to EcPV-2 infection in Chinese horses, which can serve as a causative agent for Yili horse abortions, and may thus lay the foundation for a systematic and detailed epidemiological study of this infection in Chinese horses.

Chemodynamic Therapy via Fenton and Fenton-Like Nanomaterials: Strategies and Recent Advances.

Chemodynamic therapy (CDT), a novel cancer therapeutic strategy defined as the treatment using Fenton or Fenton-like reaction to produce •OH in the tumor region, was first proposed by Bu, Shi, and co-workers in 2016. Recently, with the rapid development of Fenton and Fenton-like nanomaterials, CDT has attracted tremendous attention because of its unique advantages: 1) It is tumor-selective with low side effects; 2) the CDT process does not depend on external field stimulation; 3) it can modulate the hypoxic and immunosuppressive tumor microenvironment; 4) the treatment cost of CDT is low. In addition to the Fe-involved CDT strategies, the Fenton-like reaction-mediated CDT strategies have also been proposed, which are based on many other metal elements including copper, manganese, cobalt, titanium, vanadium, palladium, silver, molybdenum, ruthenium, tungsten, cerium, and zinc. Moreover, CDT has been combined with other therapies like chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, and immunotherapy for achieving enhanced anticancer effects. Besides, there have also been studies that extend the application of CDT to the antibacterial field. This review introduces the latest advancements in the nanomaterials-involved CDT from 2018 to the present and proposes the current limitations as well as future research directions in the related field.

AIMMS suite: a web server dedicated for prediction of drug resistance on protein mutation.

Drug resistance is one of the most intractable issues for successful treatment in current clinical practice. Although many mutations contributing to drug resistance have been identified, the relationship between the mutations and the related pharmacological profile of drug candidates has yet to be fully elucidated, which is valuable both for the molecular dissection of drug resistance mechanisms and for suggestion of promising treatment strategies to counter resistant. Hence, effective prediction approach for estimating the sensitivity of mutations to agents is a new opportunity that counters drug resistance and creates a high interest in pharmaceutical research. However, this task is always hampered by limited known resistance training samples and accurately estimation of binding affinity. Upon this challenge, we successfully developed Auto In Silico Macromolecular Mutation Scanning (AIMMS), a web server for computer-aided de novo drug resistance prediction for any ligand-protein systems. AIMMS can qualitatively estimate the free energy consequences of any mutations through a fast mutagenesis scanning calculation based on a single molecular dynamics trajectory, which is differentiated with other web services by a statistical learning system. AIMMS suite is available at http://chemyang.ccnu.edu.cn/ccb/server/AIMMS/.

Metabolic Activation and Cytotoxicity of Propafenone Mediated by CYP2D6.

Propafenone (PPF) is a class IC antidysrhythmic drug, which is commonly used for the treatment of atrial fibrillation and other supraventricular arrhythmias. It is also a ß-adrenoceptor antagonist that can cause bradycardia and bronchospasm. Hepatotoxicity is one of the adverse reactions reported, with clinical manifestations including acute cholestasis and hepatocyte necrosis. However, the mechanism of PPF-induced hepatotoxicity remains unclear. The present study was conducted to identify reactive metabolite(s) to determine related metabolic pathways and define the possible association of the bioactivation with PPF cytotoxicity. An O-demethylation phase I metabolite (M1), a further position C5 hydroxylation (para-position of the benzene ring) metabolite (M2), glutathione (GSH) conjugates (M3 and M4), and N-acetylcysteine (NAC) conjugates (M5 and M6) were detected in rat liver microsomal incubations containing PPF and GSH or NAC as trapping agents. The corresponding GSH conjugates and NAC conjugates were found in the bile and urine of rats after PPF administration, respectively. The observed GSH and NAC conjugates indicate that a quinone metabolite was generated in vitro and in vivo. Recombinant P450 enzyme incubations showed that CYP2D6 was the principal enzyme catalyzing this metabolic activation. Quinidine, a selective inhibitor of CYP2D6, attenuated the susceptibility of hepatocytes to the cytotoxicity of PPF. The results suggest that PPF was metabolized to a p-quinone intermediate which may be involved in PPF-induced hepatotoxicity.

Outbreak of neuropathogenic equid herpesvirus 1 causing abortions in Yili horses of Zhaosu, North Xinjiang, China.

BACKGROUND: EHV-1 is one of the most serious viral pathogens that frequently cause abortion in horses around the world. However, so far, relatively little information is available on EHV-1 infections as they occur in China. In January 2021, during an abortion storm which occurred in Yili horses at the Chinese State Studs of Zhaosu (North Xinjiang, China), 43 out of 800 pregnant mares aborted. RESULTS: PCR detection revealed the presence of EHV-1 in all samples as the possible cause of all abortions, although EHV-4, EHV-2 and EHV-5 were also found to circulate in the aborted fetuses. Furthermore, the partial ORF33 sequences of the 43 EHV-1 shared 99.3-100% and 99.0-100% similarity in nucleotide and amino acid sequences respectively. These sequences not only indicated a highly conserved region but also allowed the strains to group into six clusters. In addition, based on the predicted ORF30 nucleotide sequence, it was found that all the strains carried a guanine at the 2254 nucleotide position (aspartic acid at position 752 of the viral DNA polymerase) and were, therefore, identified as neuropathogenic strains. CONCLUSION: This study is the first one that establishes EHV-1 as the cause of abortions in Yili horses, of China. Further characterization of the ORF30 sequences revealed that all the EHV-1 strains from the study carried the neuropathogenic genotype. Totally, neuropathogenic EHV-1 infection in China's horse population should be concerned although the virus only detected in Yili horse abortions.

Intracellular Enzyme-Instructed Self-Assembly of Peptides (IEISAP) for Biomedical Applications.

Despite the remarkable significance and encouraging breakthroughs of intracellular enzyme-instructed self-assembly of peptides (IEISAP) in disease diagnosis and treatment, a comprehensive review that focuses on this topic is still desirable. In this article, we carefully review the advances in the applications of IEISAP, including the development of various bioimaging techniques, such as fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, positron-emission tomography imaging, radiation imaging, and multimodal imaging, which are successfully leveraged in visualizing cancer tissues and cells, bacteria, and enzyme activity. We also summarize the utilization of IEISAP in disease treatments, including anticancer, antibacterial, and antiinflammation applications, among others. We present the design, action modes, structures, properties, functions, and performance of IEISAP materials, such as nanofibers, nanoparticles, nanoaggregates, and hydrogels. Finally, we conclude with an outlook towards future developments of IEISAP materials for biomedical applications. It is believed that this review may foster the future development of IEISAP with better performance in the biomedical field.

Development and validation of 3-CpG methylation prognostic signature based on different survival indicators for colorectal cancer.

Abnormal DNA methylation is considered a vital hallmark to regulate gene expression and influence the development and progression of colorectal cancer (CRC). Although CRC-related methylation prognostic models have been developed, their clinical application is limited due to the lack of external validation and extension to other survival evaluation indicators. Therefore, this study aimed to develop and validate novel methylation prognostic models correlated with different survival indicators for individualized prognosis prediction for CRC patients. The prognostic-related CpG sites of methylation-driven genes screened by the MethylMix algorithm were identified and validated in The Cancer Genome Atlas (TCGA) CRC methylation data and our methylation data. The prognostic models correlated with different survival evaluation indicators (overall survival [OS] and disease-free survival [DFS]) were developed and validated in the TCGA CRC dataset (N = 376) and our independent CRC dataset (N = 227). We utilized the combination of selected 3-CpG methylation sites in three genes (DAPP1, FAM3D, and PIGR) to construct a prognostic risk-score model. In the training dataset, Kaplan-Meier survival analysis demonstrated that high-risk patients had significantly poorer survival than low-risk patients (pOS = .0014; pDFS < .001). Then, the 3-CpG methylation signature was successfully validated as an independent predictor in the testing data set (pOS = .016; pDFS = .016). A prognostic nomogram was constructed and validated. Additionally, mediation analysis revealed the direct effect of the methylation signature on CRC prognosis (pOS = 9.149e-06; pDFS = .001). In summary, our study revealed that the 3-CpG methylation signature might be a potential prognostic indicator to facilitate individualized survival prediction for CRC patients.

First detection and genetic characterization of equid herpesvirus 2, 4, and 5 in China.

In November 2018, an outbreak of respiratory disease occurred in foals at an equestrian club in Changji, northern Xinjiang, China. We applied viral metagenomics to investigate this outbreak and identify potential pathogens involved in this equine respiratory syndrome. The metagenomics data revealed the presence of sequences matching those of equid herpesvirus (EHV) 2, 4, and 5. PCR with specific primers targeting ORF33 of EHV-4 and ORF8 of EHV-2 and EHV-5 revealed coinfection with these viruses in this respiratory syndrome. To investigate the prevalence of these viruses in China, 453 nasal swabs from clinically healthy thoroughbred foals (36/453, 7.9%) and horses (417/453, 92.1%) were collected from several equestrian clubs. Forty-five (9.9%) of the samples tested positive for EHV-5 DNA, and seven (1.5%) tested positive for EHV-2, but all were negative for EHV-4 DNA. Forty-nine (10.8%) samples tested positive for both EHV-5 and EHV-2 DNA. Using these samples, one complete EHV-4 ORF33, 10 partial EHV-2 ORF8, and 50 partial EHV-5 ORF8 sequences from the 10 diseased foals and 50 thoroughbred horses were then determined. Sequence analysis indicated that EHV-4 ORF33 and EHV-5 ORF8, in contrast to EHV-2 ORF8, had high sequence similarity to those of published sequences. Our data provide the first evidence that EHV-2, -4, and -5 co-circulate in China and that EHV-4 is potentially involved in this respiratory disease in foals.

InsectiPAD: A Web Tool Dedicated to Exploring Physicochemical Properties and Evaluating Insecticide-Likeness of Small Molecules.

The concept of insecticide-likeness is valuable to select more promising lead candidates during the early stages of drug discovery. We analyzed the physicochemical properties of commercial insecticides and optimized available drug-likeness scoring functions to quantitatively evaluate the insecticidal-like potential of compounds. An interactive platform named Insecticide Physicochemical-properties Analysis Database (InsectiPAD) was developed, which covers 495 approved insecticides and over 22 200 related physicochemical properties. More importantly, it contains over 2900 qualitative analyses and 1500 quantitative scores for insecticides and provides comprehensive insecticide-likeness analysis for any compound. The accuracy and ability of InsectiPAD to distinguish known insecticides (positive sample) from other compounds (negative sample) was also assessed, which is around 75%. Simple input and efficient interpretation are ensured to be useful and helpful for insecticide discovery.

Hepatic Pedicle Occlusion with the Pringle Maneuver During Difficult Laparoscopic Cholecystectomy Reduces the Conversion Rate.

BACKGROUND: In the presence of cholecystitis or portal hypertension, hemorrhage is common during laparoscopic cholecystectomy (LC) because the vessels of Calot's triangle are fragile and tortuous. Bleeding can obstruct surgical field visibility and increase conversion rates and risk of common bile duct injury. The Pringle maneuver is a simple occlusion approach that could limit blood flow from the hepatic pedicle, thus controlling bleeding to provide a clear surgical field to reduce conversion rate. In this study, we aimed to investigate the feasibility, effectiveness and safety of hepatic pedicle occlusion with the Pringle maneuver during difficult LC. METHODS: From 2011 to 2015, LC with hepatic pedicle occlusion by the Pringle maneuver was performed in 67 patients (Pringle group). Another group of 67 cases with matched clinical parameters where LC was performed without the Pringle maneuver (non-Pringle group) was retrieved from a database to serve as the control group. RESULTS: The Pringle group had a significantly lower conversion rate (1.49% vs. 11.9%; P = 0.038), less blood loss (37.5 ± 24.1 mL vs. 94.5 ± 67.8 mL; P = 0.002), shorter postoperative hospitalization (2.5 ± 1.4 days vs. 3.5 ± 2.5 days; P = 0.005), and lower cost ($1343 ± $751 USD vs. $1674 ± $609 USD; P = 0.024) than non-Pringle group. There was one case each of bile duct injury and readmission within 30 days because of bile leakage in the non-Pringle group, but none in the Pringle group. CONCLUSIONS: Hepatic pedicle occlusion could provide a clear surgical field and enable the recognition of structures during LC. The Pringle maneuver offers a feasible and safe approach to lower conversion rates in difficult LC.

A Concise Synthesis of (-)-Ambrox.

(-)-Ambrox, a highly prized and commercially significant component of ambergris, finds widespread application in perfumery, cigarettes, cosmetics, and the food industry. Despite considerable attention to this research area over the years, an environmentally friendly and practical method for synthesizing (-)-ambrox has remained elusive. This study presents a succinct and efficient approach to (-)-ambrox synthesis, involving two consecutive alkylations at C-6, followed by an acid-catalyzed cyclization to give bicyclic ketones starting from (R)-carvone. Subsequent reduction, Barton Vinyl Iodide synthesis, alkylation, and an acid-catalyzed cyclization collectively achieved the synthesis of (-)-ambrox with a satisfactory yield of 26.2 %.

Mechanism-based cytotoxicity trend prediction of furan-containing pollutants present in a mixture.

Human exposure to furan-containing pollutants (FCPs) has raised concerns due to their high risk of toxicity. A substantial number of approximately 8500 recorded compounds containing a furan ring exist which have been analytically or in biologically studied. A significant portion of these compounds is found in the everyday environments of individuals, particularly when ingested through food. Consequently, there is a need for a universal approach to rapidly predict the potential toxicity trends of FCPs. In this study, we developed a bromine labeling-based platform that combines LC-ICP-MS and LC-ESI-MS techniques to absolutely quantify FCP-induced protein adduction. The LC-ESI-MS approach facilitated the identification of FCP-derived protein adducts and optimized liquid chromatographic conditions for analyte separation. By employing a well-designed bromine-containing compound as a general internal standard, LC-ICP-MS-based technique enabled to absolutely assess bromine-labeled protein adduction. The protein adduction efficiencies of furan, 2-methylfuran, and 2,5-dimethylfuran were found to be 2.68, 2.90, and 0.37 molecules per 10,000 FCP molecules that primary hepatocytes received, respectively. Furthermore, we observed that 2-methylfuran exhibited the highest cytotoxicity, followed by furan and 2,5-dimethylfuran, which aligned with the order of their protein adduction. Thus, the protein adduction efficiency of FCPs could serve as a potential index for predicting their toxicity trends.

Blockade of Hepatocyte PCSK9 Ameliorates Hepatic Ischemia-Reperfusion Injury by Promoting Pink1-Parkin-Mediated Mitophagy.

BACKGROUND & AIMS: Hepatic ischemia-reperfusion injury is a significant complication of partial hepatic resection and liver transplantation, impacting the prognosis of patients undergoing liver surgery. The protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily synthesized by hepatocytes and has been implicated in myocardial ischemic diseases. However, the role of PCSK9 in hepatic ischemia-reperfusion injury remains unclear. This study aims to investigate the role and mechanism of PCSK9 in hepatic ischemia-reperfusion injury. METHODS: We first examined the expression of PCSK9 in mouse warm ischemia-reperfusion models and AML12 cells subjected to hypoxia/reoxygenation. Subsequently, we explored the impact of PCSK9 on liver ischemia-reperfusion injury by assessing mitochondrial damage and the resulting inflammatory response. RESULTS: Our findings reveal that PCSK9 is up-regulated in response to ischemia-reperfusion injury and exacerbates hepatic ischemia-reperfusion injury. Blocking PCSK9 can alleviate hepatocyte mitochondrial damage and the consequent inflammatory response mediated by ischemia-reperfusion. Mechanistically, this protective effect is dependent on mitophagy. CONCLUSIONS: Inhibiting PCSK9 in hepatocytes attenuates the inflammatory responses triggered by reactive oxygen species and mitochondrial DNA by promoting PINK1-Parkin-mediated mitophagy. This, in turn, ameliorates hepatic ischemia-reperfusion injury.

Antibacterial Chemodynamic Therapy: Materials and Strategies.

The wide and frequent use of antibiotics in the treatment of bacterial infection can cause the occurrence of multidrug-resistant bacteria, which becomes a serious health threat. Therefore, it is necessary to develop antibiotic-independent treatment modalities. Chemodynamic therapy (CDT) is defined as the approach employing Fenton and/or Fenton-like reactions for generating hydroxyl radical (•OH) that can kill target cells. Recently, CDT has been successfully employed for antibacterial applications. Apart from the common Fe-mediated CDT strategy, antibacterial CDT strategies mediated by other metal elements such as copper, manganese, cobalt, molybdenum, platinum, tungsten, nickel, silver, ruthenium, and zinc have also been proposed. Furthermore, different types of materials like nanomaterials and hydrogels can be adopted for constructing CDT-involved antibacterial platforms. Besides, CDT can introduce some toxic metal elements and then achieve synergistic antibacterial effects together with reactive oxygen species. Finally, CDT can be combined with other therapies such as starvation therapy, phototherapy, and sonodynamic therapy for achieving improved antibacterial performance. This review first summarizes the advancements in antibacterial CDT and then discusses the present limitations and future research directions in this field, hoping to promote the development of more effective materials and strategies for achieving potentiated CDT.

Prognostic scoring system based on eosinophil- and basophil-related markers for predicting the prognosis of patients with stage II and stage III colorectal cancer: a retrospective cohort study.

Background: Systemic inflammation is associated with the prognosis of colorectal cancer (CRC). The current study aimed to construct a comprehensively inflammatory prognostic scoring system named risk score (RS) based on eosinophil- and basophil-related markers and assess its prognostic value in patients with stage II and stage III CRC. Patients and methods: A total of 3,986 patients were enrolled from January 2007 to December 2013. The last follow-up time was January 2019. They were randomly assigned to the training set and testing set in a 3:2 split ratio. Least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was performed to select the optimal prognostic factors in the construction of RS. The Kaplan-Meier curve, time-dependent receiver operating characteristic (ROC), and Cox analysis were used to evaluate the association between RS and overall survival (OS). Results: In the training set, all inflammatory markers showed certain prognostic values. Based on LASSO-Cox analysis, nine markers were integrated to construct RS. The Kaplan-Meier curve showed that a higher RS (RS > 0) had a significantly worse prognosis (log-rank p< 0.0001). RS (>0) remained an independent prognostic factor for OS (hazard ratio (HR): 1.70, 95% confidence interval (CI), 1.43-2.03, p< 0.001). The prognostic value of RS was validated in the entire cohort. Time-dependent ROC analysis showed that RS had a stable prognostic effect throughout the follow-up times and could enhance the prognostic ability of the stage by combination. Nomogram was established based on RS and clinicopathological factors for predicting OS in the training set and validated in the testing set. The area under the curve (AUC) values of the 3-year OS in the training and testing sets were 0.748 and 0.720, respectively. The nomogram had a satisfactory predictive accuracy and had better clinical application value than the tumor stage alone. Conclusions: RS might be an independent prognostic factor for OS in patients with stage II and III CRC, which is helpful for risk stratification of patients. Additionally, the nomogram might be used for personalized prediction and might contribute to formulating a better clinical treatment plan.

Survival of Patients Subjected to Hepatectomy After Spontaneous Rupture of Hepatocellular Carcinoma: A Meta-analysis of High-quality Propensity Score Matching Studies.

Background: The spontaneous rupture of hepatocellular carcinoma (HCC) is associated with high mortality rates, and liver resection can provide better outcomes than other available treatments. However, the survival length of patients subjected to hepatectomy after spontaneous rupture of hepatocellular carcinoma remains controversial. Method: Articles reporting the comparison of the survival outcome between patients with rupture HCC (rHCC) and non-rupture HCC (nrHCC) from the inception until December 31, 2021 by PubMed, Web of Science, OVID, and the Cochrane Library databases were included. The high-quality propensity score matching analysis was used to investigate the impact of rupture on disease-free survival (DFS) and overall survival (OS) between the rHCC and nrHCC group with no heterogeneity. Result: A total of 606 patients from six cohort studies were included. The major baseline characteristics of the eligible patients were well balanced between rHCC and nrHCC group. The 1-, 3-, and 5-year hazard ratios of DFS were 3.45 (95% confidence interval [CI] 2.54-4.68), 3.63 (95% CI 2.87-4.60), and 3.72 (95% CI 2.93-4.72), respectively. The 1-, 3-, and 5-year hazard ratios of OS were 5.01 (95% CI 3.26-7.69), 5.49 (95% CI 4.08-7.39), and 4.20 (95% CI 3.20-5.51), respectively. Conclusion: The present meta-analysis demonstrated that the DSF and OS were significantly shorter in the rHCC group than in the nrHCC group, thus revealing that spontaneous HCC rupture was a predictor of poor survival.