Quercetin: a promising virulence inhibitor of Pseudomonas aeruginosa LasB in vitro.

With the inappropriate use of antibiotics, antibiotic resistance has emerged as a major dilemma for patients infected with Pseudomonas aeruginosa. Elastase B (LasB), a crucial extracellular virulence factor secreted by P. aeruginosa, has been identified as a key target for antivirulence therapy. Quercetin, a natural flavonoid, exhibits promising potential as an antivirulence agent. We aim to evaluate the impact of quercetin on P. aeruginosa LasB and elucidate the underlying mechanism. Molecular docking and molecular dynamics simulation revealed a rather favorable intermolecular interaction between quercetin and LasB. At the sub-MICs of ≤256 µg/ml, quercetin was found to effectively inhibit the production and activity of LasB elastase, as well as downregulate the transcription level of the lasB gene in both PAO1 and clinical strains of P. aeruginosa. Through correlation analysis, significant positive correlations were shown between the virulence gene lasB and the QS system regulatory genes lasI, lasR, rhlI, and rhlR in clinical strains of P. aeruginosa. Then, we found the lasB gene expression and LasB activity were significantly deficient in PAO1 ΔlasI and ΔlasIΔrhlI mutants. In addition, quercetin significantly downregulated the expression levels of regulated genes lasI, lasR, rhlI, rhlR, pqsA, and pqsR as well as effectively attenuated the synthesis of signaling molecules 3-oxo-C12-HSL and C4-HSL in the QS system of PAO1. Quercetin was also able to compete with the natural ligands OdDHL, BHL, and PQS for binding to the receptor proteins LasR, RhlR, and PqsR, respectively, resulting in the formation of more stabilized complexes. Taken together, quercetin exhibits enormous potential in combating LasB production and activity by disrupting the QS system of P. aeruginosa in vitro, thereby offering an alternative approach for the antivirulence therapy of P. aeruginosa infections. KEY POINTS: • Quercetin diminished the content and activity of LasB elastase of P. aeruginosa. • Quercetin inhibited the QS system activity of P. aeruginosa. • Quercetin acted on LasB based on the QS system.

Effect of piperine on the inhibitory potential of MexAB-OprM efflux pump and imipenem resistance in carbapenem-resistant Pseudomonas aeruginosa.

The escalating prevalence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a significant threat to global public health through the spread of its 'high-risk' clones. Immediate and decisive research into antimicrobial agents against CRPA is crucial for the development of effective measures and interventions. Overexpression of the MexAB-OprM efflux pump is one of the major mechanisms of CRPA. Since the active efflux of antibacterial agents plays a significant role in mediating drug resistance in CRPA, the inhibition of efflux pumps has become a promising strategy to restore antibacterial potency. Piperine (PIP) has been proven to be a promising efflux pump inhibitor in some bacteria. However, there are no studies on whether PIP can act as a potential efflux pump inhibitor in CRPA. The present study aimed to identify the antibacterial activity of PIP against CRPA and to evaluate the effect on the MexAB-OprM efflux pump. Molecular docking was used to analyze the possible interaction of PIP with the proteins of the MexAB-OprM efflux pump in CRPA. The effect of PIP on the expression of the MexAB-OprM efflux pump was investigated by real-time quantitative PCR (qPCR) and ethidium bromide accumulation efflux assay. The effect of PIP on CRPA imipenem (IPM) resistance was investigated by the checkerboard dilution method. The results demonstrated that PIP exhibited the lowest binding affinity of -9.1 kcal towards efflux pump proteins. A synergistic effect between PIP and IPM on CRPA was observed. More importantly, PIP effectively hindered the efflux of ethidium bromide and IPM by up-regulating MexR gene expression while down-regulating MexA, MexB, and OprM gene expressions. In conclusion, PIP could enhance the antibacterial activity of IPM by inhibiting the MexAB-OprM efflux pump. Our work proved that PIP had the potential to be an efflux pump inhibitor of CRPA.

Regulation of saturation magnetization of magnetite by doping with group III elements.

Magnetic Fe3O4 nanoparticles show promising applications in nanomedicine. However, the saturation magnetization (MS) of Fe3O4 nanoparticles synthesized in laboratory is usually not high enough, which greatly limits their application in drug delivery and magnetic hyperthermia. Here, by accurate hybrid density functional computation, the doping behavior of group III elements (including Al, Ga, and In) and the effects on magnetic and electronic properties are well studied. The results show that the doping behavior depends on the concentration of dopants. Interestingly, appropriate Ga and In doping concentrations can significantly increase the MS of Fe3O4. In addition, the doping of group III elements (Al, Ga and In) into Fe3O4 would not induce any defect states in the band gap but slightly increases the band gap. Our results provide a simple and feasible scheme for increasing the MS of magnetite, which is significant for the applications of Fe3O4 nanoparticles in drug delivery and magnetic hyperthermia.

Efficacy of prophylactic negative pressure wound therapy after open ventral hernia repair: a systematic review meta-analysis.

INTRODUCTION: The susceptibility to surgical site occurrence (SSO) is high following ventral hernia repair (VHR) surgery. SSO severely increases the physical and mental burden on patients. The main purpose of this review was to analyze the efficacy of negative pressure wound therapy (NPWT) after open VHR(OVHR) and explore benefits to patients. METHODS: The Cochrane Library, PubMed, and Embase databases were searched from the date of establishment to 15 October 2022. All randomized controlled trials and retrospective cohort studies comparing NPWT with standard dressings after OVHR were included. The Revman 5.4 software recommended by Cochrane and the STATA16 software were used in this meta-analysis. RESULTS: Fifteen studies (involving 1666 patients) were identified and included in the meta-analysis, with 821 patients receiving NPWT. Overall, the incidence rate of SSO in the NPWT group was lower compared to the control group (odds ratio [OR] = 0.44; 95% confidence interval [CI] = 0.21-0.93; I2 = 86%; P = 0.03). The occurrence rate of surgical site infection (SSI; OR = 0.51; 95% CI = 0.38-0.68, P < 0.001), wound dehiscence (OR = 0.64; 95% CI = 0. 43-0.96; P = 0.03), and hernia recurrence (OR = 0.51; 95% CI = 0.28-0.91, P = 0.02) was also lowered. There was no significant difference in seroma (OR = 0.76; 95% CI = 0.54-1.06; P = 0.11), hematoma (OR = 0.53; 95% CI = 0.25-1.11; P = 0.09), or skin necrosis (OR = 0.83; 95% CI = 0.47-1.46; P = 0.52). CONCLUSION: NPWT can effectively decrease the occurrence of SSO, SSI wound dehiscence and hernia recurrence and should be considered following OVHR.

A propensity score-matched analysis of laparoscopic versus open surgical radical resection for gastric gastrointestinal stromal tumor.

Background: Surgery is the mainstay of treatment for gastric gastrointestinal stromal tumours (GIST). However, the choice of surgical approach for gastric GIST remains controversial. Aims and Objectives: To evaluate the short- and long-term efficacies of laparoscopic surgery versus conventional open surgery for gastric GIST. Materials and Methods: We retrospectively reviewed 148 patients with gastric GIST at our hospital between January 2013 and January 2020. The patients were categorised into the following two groups based on the surgery performed: The laparoscopic surgery group (LG) and the open surgery group (OG). Differences in the tumour size, surgical procedures and modified National Institutes of Health classification were statistically significant. To balance the intergroup confounders, we performed 1:1 propensity score matching (PSM). Results: A total of 104 patients were selected after PSM (52 in each group). We focused on the short- and long- term outcomes of patients. The baseline information was balanced between the two groups after PSM. The LG benefited from the advantages of a minimally invasive surgery (faster gastrointestinal function recovery, shorter time to drainage tube removal, less blood loss and shorter hospitalisation period), however, it also had high treatment costs. Moreover, both laparoscopic and open surgeries resulted in similar intra-operative and post-operative complications rates, overall survival time and disease-free survival time. Conclusion: Laparoscopic resection is feasible and oncologically safe for GIST. However, more prospective studies are required to confirm the findings.

Update on risk factors of surgical site infection in colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: Surgical site infection (SSI) in colorectal cancer (CRC) has been a serious health care problem due to the delay of postoperative recovery. Our present study aimed to explore the risk factors for SSI in CRC patients. METHODOLOGY: We have systematically searched these databases: PubMed, Cochrane Library, and EMBASE as of March 2020 for studies on risk factors associated with SSI. Two investigators independently conducted the quality assessment and data extraction. Related risk factors in the studies were recorded, and a meta-analysis was performed. RESULTS: The search initially provided 2262 hits, 1913 studies were screened by two independent investigators. Finally, 15 studies were identified to be relevant for this meta-analysis. In total, 25 risk factors were eligible. Our meta-analysis indicated that eight factors (obesity, male sex, diabetes mellitus, ASA score ≥ 3, stoma creation, intraoperative complications, perioperative blood transfusion, and operation time ≥ 180 min) were significant risk factors for SSI, and one factor (laparoscopic procedure) was protective for SSI. CONCLUSIONS: Effective interventions targeting the above factors may reduce the risk of developing postoperative SSI in CRC patients and improve the clinical outcome of patients. Further prospective studies are needed to confirm these findings.

Research trends on the gut-brain axis: A bibliometric analysis.

Core Tip: This was the first bibliometric analysis of gut-brain axis, analyzing the current status and future trends. The annual publication output would be constantly increasing in the future. Future research hotspots would focus on the pathogenesis research and therapy of gut-brain related diseases.

Update on the relationship between inflammatory bowel disease and colorectal cancer: Global research status and trends.

Core Tip: This was the first bibliometric analysis between inflammatory bowel disease and colorectal cancer, analyzing the current status and future trends. The annual publication output would be constantly increasing in the future. Future research hotspots would focus on the pathogenesis research and targeted therapy.

METTL16 regulates the mRNA stability of FBXO5 via m6A modification to facilitate the malignant behavior of breast cancer.

BACKGROUND: N6-methyladenosine (m6A) regulates the progression of breast cancer (BC). We aimed to investigate the action and mechanism involved of methyltransferase-like protein 16 (METTL16) in BC growth and metastasis. METHODS: RT-qPCR, immunoblotting, and IHC were performed to test the levels of gene expression. CCK-8, clone formation, wound healing, and transwell assays were applied to measure the cell proliferation, migration, and invasion. m6A RNA methylation and MeRIP assay were utilized to confirm the m6A level of total RNA and FBXO5 mRNA. RIP was utilized to ascertain the interaction between METTL16 and FBXO5 mRNA. The in vivo murine subcutaneous tumor and metastasis model were constructed to further confirm the action of METTL16. RESULTS: METTL16 was overexpression in BC cells and tissues. Inhibition of METTL16 restrained the growth and metastasis of BC. Furthermore, the METTL16 level and FBXO5 level was positively correlated in BC tissues, and METTL16 aggrandized the stability of FBXO5 mRNA depending on the m6A modification. Overexpression of FBXO5 antagonized the restrained function of METTL16 knockdown on BC cells' proliferation, migration, invasion, and EMT. CONCLUSION: METTL16 boosts the mRNA stability of FBXO5 via m6A modification to facilitate the malignant action of BC in vitro and in vivo, offering new latent targets for cure of BC.

Mutation of Pseudomonas aeruginosa lasI/rhlI diminishes its cytotoxicity, oxidative stress, inflammation, and apoptosis on THP-1 macrophages.

The management of Pseudomonas aeruginosa (P. aeruginosa) infections presents a substantial challenge to clinics and public health, emphasizing the urgent need for innovative strategies to address this issue. Quorum sensing (QS) is an intercellular communication mechanism that coordinates bacterial activities involved in various virulence mechanisms, such as acquiring host nutrients, facilitating biofilm formation, enhancing motility, secreting virulence factors, and evading host immune responses, all of which play a crucial role in the colonization and infection of P. aeruginosa. The LasI/R and RhlI/R sub-systems dominate in the QS system of P. aeruginosa. Macrophages play a pivotal role in the host's innate immune response to P. aeruginosa invasion, particularly through phagocytosis as the initial host defense mechanism. This study investigated the effects of P. aeruginosa's QS system on THP-1 macrophages. Mutants of PAO1 with lasI/rhlI deletion, as well as their corresponding complemented strains, were obtained, and significant downregulation of QS-related genes was observed in the mutants. Furthermore, the ΔlasI and ΔlasIΔrhlI mutants exhibited significantly attenuated virulence in terms of biofilm formation, extracellular polymeric substances synthesis, bacterial adhesion, motility, and virulence factors production. When infected with ΔlasI and ΔlasIΔrhlI mutants, THP-1 macrophages exhibited enhanced scavenging ability against the mutants and demonstrated resistance to cytotoxicity, oxidative stress, inflammatory response, and apoptosis induced by the culture supernatants of these mutant strains. These findings offer novel insights into the mechanisms underlying how the lasI/rhlI mutation attenuates cytotoxicity, oxidative stress, inflammation, and apoptosis in macrophages induced by P. aeruginosa.IMPORTANCEP. aeruginosa is classified as one of the ESKAPE pathogens and poses a global public health concern. The QS system of this versatile pathogen contributes to a broad spectrum of virulence, thereby constraining therapeutic options for serious infections. This study illustrated that the lasI/rhlI mutation of the QS system plays a prominent role in attenuating the virulence of P. aeruginosa by affecting bacterial adhesion, biofilm formation, extracellular polymeric substances synthesis, bacterial motility, and virulence factors' production. Notably, THP-1 macrophages infected with mutant strains exhibited increased phagocytic activity in eliminating intracellular bacteria and enhanced resistance to cytotoxicity, oxidative stress, inflammation, and apoptosis. These findings suggest that targeted intervention toward the QS system is anticipated to diminish the pathogenicity of P. aeruginosa to THP-1 macrophages.

The transcription factor ZNF248 promotes colorectal cancer metastasis by binding to ZEB1.

Colorectal cancer (CRC) is one of the most common malignant tumors globally, with metastasis emerging as the leading cause of mortality in CRC patients. Transcription factors play pivotal roles in the metastatic process. Using bioinformatics tools, we analyzed the TCGA-COAD and GES146587 datasets and identified ZNF248 participating in tumor progression. By analyzing 100 CRC patient tissues, it is found that ZNF248 is highly expressed in cancer tissue as well as in CRC cell lines identified by qRT-PCR. Our study discovered that ZNF248 enhances CRC cell migratory and invasive capabilities. A positive correlation was found between ZNF248 and epithelial-mesenchymal transition (EMT)-related markers (ZEB1, snail1), while E-cadherin exhibited a negative correlation with ZNF248. In addition, the analysis of the TCGA dataset demonstrated a strong correlation between the mRNA level of ZNF248 and ZEB1 expressions. Furthermore, it is found that the overexpression of ZEB1 could reverse CRC cell invasion and migration, along with the inhibition on EMT marker expressions induced by the RNA interference with ZNF248. Immunohistochemical analysis indicated a substantial association of ZNF248 expression with the lymph node metastasis, and with the liver metastasis (P =0.01, P =0.01), and a positive correlation between ZNF248 and ZEB1 expression (P =0.021) was also identified. Using Chip-PCR assay, it is found that ZNF248 bound to the ZEB1 promoter region. These findings showed that ZNF248 promotes CRC metastasis in vivo, revealed its role as an oncogene in CRC by targeting ZEB1 and activating the EMT pathway, which provided novel and promising biomarkers for CRC therapy through targeting ZEB1.

A unicentric center, multicenter, and mixed-type Castleman disease: Three case reports and a review of the literature.

RATIONALE: Due to the lack of specificity symptoms and site of onset of castleman disease (CD), it is difficult to diagnose and poses unique challenges for both patients and clinicians, leading to confusion in diagnosis and delays in treatment. To enhance understanding, we present 3 cases of CD treated at our hospital, including a single-center, multicenter, and mixed-type CD. PATIENT CONCERNS: Case 1: A 53-year-old female patient was admitted with a chief complaint of "abdominal pain and fever for 10 days." Marked enlargement of inguinal lymph nodes on both sides was observed. Case 2: A 58-year-old female patient was admitted with the main complaint of "discovering a left lower abdominal mass during a routine checkup for the past 10 days." Upon deep palpation, a palpable mass of approximately 5.0 * 3.0 cm was identified in the left lower abdomen. Case 3: A 40-year-old male patient was admitted with the main complaint of "progressive right upper abdominal and lumbar back pain for over 6 months." Computed tomography examination revealed multiple nodular soft tissue masses between the abdominal aorta and inferior vena cava, with the largest measuring 5.0 * 4.0 cm. DIAGNOSES: Based on the immunohistochemical results, the diagnoses for the 3 patients are as follows: Case 1: Multicentric Castleman's Disease (Mixed Type). Case 2: Pelvic Retroperitoneal Castleman Disease (Hyaline Vascular Type). Case 3: Castleman Disease Multicentric Type. INTERVENTION: Case 1: cyclophosphamide 0.6-1 g + vincristine 2 mg + methylprednisolone 50 mg/5 days. Cyclophosphamide 1 g + prednisone 30-50 mg/5 days. This alternating chemotherapy cycle is repeated every 6 months. Case 2: Laparoscopic pelvic mass excision surgery. Case 3: Surgical excision of the mass. OUTCOMES: Case 1: After a 43-month follow-up, the patient's general symptoms have improved compared to before, but regular chemotherapy is still necessary at present. Case 2: The patient did not take any medication postoperatively, and there has been no evidence of metastasis or recurrence during the 18-month follow-up. Case 3: The patient did not take any medication, and there has been no evidence of metastasis or recurrence during the 21-month follow-up. LESSONS SUBSECTIONS: The lack of specific signs on imaging studies and nonspecific blood tests increases the difficulty of diagnosis. However, tissue biopsy remains a feasible option. Therefore, we recommend conducting thorough examinations for suspected CD patients to reduce misdiagnosis and determine the CD type for effective targeted treatment.

Characterization and genomic analysis of a broad-spectrum lytic phage HZ2201 and its antibiofilm efficacy against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a clinically common conditionally pathogenic bacterium, and the abuse of antibiotics has exacerbated its drug resistance in recent years. This has resulted in extensive reports about the usage of Pseudomonas aeruginosa phage as a novel antibacterial drug. In this study, we isolated a novel phage HZ2201 with a broad lytic spectrum. The lytic rate of this phage against Pseudomonas aeruginosa reached 78.38% (29/37), including 25 multi-drug- and carbapenem-resistant Pseudomonas aeruginosa strains. Transmission electron microscopy revealed that phage HZ2201 belongs to the class Caudoviricetes. Biological characterization showed that phage HZ2201 had an latent period of 40 min, a lytic period of 20 min, and a burst size of 440 PFU/cell, with improved tolerance to temperature and pH. Considering genomic analysis, the HZ2201 genome was a circular double-stranded DNA with a size of 45,431 bp and a guanine-cytosine (G + C) content of 52.16%, and contained 3 tRNAs. 27 of the 74 open reading frames (ORFs) annotated by the Rapid Annotation using Subsystem Technology (RAST) tool could be matched to the genomes of known functions, and no genes related to virulence and antibiotic resistance were found. The phylogenetic tree suggests that phage HZ2201 is highly related to the phage ZCPS1 and PaP3, and ORF57 and ORF17 are predicted to encode a holin and an endolysin, respectively. Cell lysis by HZ2201 proceeds through the holin-endolysin system, suggesting that it is a novel phage. Additionally, we demonstrated that phage HZ2201 has a high inhibitory capacity against Pseudomonas aeruginosa biofilms. The results of our study suggest that phage HZ2201 is a novel potential antimicrobial agent for treating drug-resistant Pseudomonas aeruginosa infection.

The risk factors of low anterior resection syndrome after colorectal cancer surgery: A retrospective study of 566 patients in a single institution in China.

Purpose: This study aims to identify the independent risk factors in the low anterior resection syndrome (LARS) after surgery for colorectal cancer (CRC). Method: This was a retrospective, single-institution study in the Second Affiliation Hospital of Dalian Medical University, China. Patients underwent sphincter-preserving low anterior resection with total or partial mesorectal resection (with or without protective ileostomy) and completed a self-filled questionnaire over the phone to assess postoperative bowel dysfunction from January 2017 to December 2019. The predictors of LAR were evaluated using univariate and multivariate analyses. Result: The study population was 566 patients, 264 (46.64%), 224 (39.58%), and 78 (13.78%) patients with no, minor, and major LARS, respectively. In the univariate analysis, independent factors such as tumor location and size, anastomotic height, protective ileostomy, post-operation chemoradiotherapy, tumor T stage, lymphatic nodal metastasis classification, surgery duration, and time interval for closure of stoma were significantly associated with LARS points while we found the tumor T stage and lymphatic nodal metastasis classification as the new independent risk factors compared with the last decade studies. In the multivariate analysis, factors such as low and middle tumor location and protective ileostomy, and post operation treatment, nodal metastasis classification were the independent risk factors for major LARS. Conclusion: The new independence risk factors were tumor T stage and lymphatic nodal metastasis status in univariate analysis in our study, with anastomotic height, low and middle tumor location, protective ileostomy, post-operation chemoradiotherapy, nodal metastasis status increasing LARS point in multivariate analysis after surgery for CRC.

Surgical treatment of locally advanced right colon cancer invading neighboring organs.

Purpose: Invasion of the pancreas and/or duodenum with/without neighboring organs by locally advanced right colon cancer (LARCC) is a very rare clinical phenomenon that is difficult to manage. The purpose of this review is to suggest the most reasonable surgical approach for primary right colon cancer invading neighboring organs such as the pancreas and/or duodenum. Methods: An extensive systematic research was conducted in PubMed, Medline, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) using the MeSH terms and keywords. Data were extracted from the patients who underwent en bloc resection and local resection with right hemicolectomy (RHC), the analysis was performed with the survival rate as the outcome parameters. Results: As a result of the analysis of 117 patient data with locally advanced colon cancer (LACC) (73 for males, 39 for females) aged 25-85 years old from 11 articles between 2008 and 2021, the survival rate of en bloc resection was 72% with invasion of the duodenum, 71.43% with invasion of the pancreas, 55.56% with simultaneous invasion of the duodenum and pancreas, and 57.9% with invasion of neighboring organs with/without invasion of duodenum and/or pancreas. These survival results were higher than with local resection of the affected organ plus RHC. Conclusion: When the LARCC has invaded neighboring organs, particularly when duodenum or pancreas are invaded simultaneously or individually, en bloc resection is a reasonable option to increase patient survival after surgery.

Systematic Analysis of E2F Expression and Its Relation in Colorectal Cancer Prognosis.

Background: The E2 factor (E2F) family of transcription factors is dysregulated in numerous cancer types and may play a vital role in the development of various malignancies. However, to our knowledge, the specific function of each of the E2Fs and their relation to the disease prognosis of colorectal cancer (CRC) patients remain unknown. Materials and Methods: We used different publicly available databases and tools, such as ONCOMINE, GEPIA2, UALCAN, cBioPortal, Kaplan-Meier plotter, Metascape, and TIMER analysis, to do an in silico exploration of the potential roles of E2Fs in CRC. Results: In our analyses, we found a downregulation of E2F2 expression and an upregulation of E2F1 and E2F3-8 expression in CRC tissues compared to normal controls. These findings were consistent with our subgroup analysis using the different clinicopathological features of CRC patients. Furthermore, overexpression of E2F3 and E2F4 were significantly correlated with worse overall survival (OS) in colon cancer patients. Meanwhile, low levels of E2F2 resulted in a shorter OS in rectal cancer patients. The E2F family members had varying degrees of genetic alterations with the highest alteration rate observed in E2F1 (23%). Interestingly, a moderate positive express correlation had been found in the following E2F family members: E2F1 with E2F4, E2F2 with E2F7, E2F2 with E2F8, and E2F7 with E2F8. In addition, spearman analysis revealed that E2Fs have a strong positive correlation with the critical oncogenes in CRC patients. Lastly, the expression of E2Fs was significantly associated with the infiltration of six immune cells. Conclusion: In this study, we found that E2F2, E2F3, and E2F4 have the potential to be novel prognostic biomarkers in CRC. The role of these E2F family members in disease pathology may be related to their functions in cell cycle regulation, therapeutic resistance, immune cell infiltration, and epithelia-to-mesenchymal transition. Further studies are required to validate our results; however, our findings may help provide a foundation for broadening our understanding of CRC pathology.

Recent Advancements in the Treatment of Rectal Gastrointestinal Stromal Tumor: In Era of Imatinib.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of the gastrointestinal tract, with an annual incidence of 10-15 cases per million. However, rectal GIST has a low incidence, accounting for approximately 0.1% of all rectal tumors. The treatment of rectal GISTs is still controversial and the relative unified guidelines and consensus opinions are inadequate. Treatment is based primarily on the clinical experience of the physician. The widespread application of neoadjuvant imatinib therapy allows diversification of treatment, especially in the choice of surgical methods. Herein, we reviewed the most recent literature and summarized the new progress in rectal tumor treatment, with the aim of providing patients with more systematic and individualized therapeutic strategies.

The analysis of prognostic factors of primary small intestinal gastrointestinal stromal tumors with R0 resection: A single-center retrospective study.

OBJECTIVE: We aim to assess factors that affect overall survival in patients with primary small intestinal gastrointestinal stromal tumors (GISTs) who had undergone R0 resection. METHOD: A retrospective analysis reviewed the data of 82 consecutive confirmed GIST patients at a single medical center in China from January 2012 to June 2020. The survival curve was estimated using the Kaplan-Meier method, and independent prognostic factors were confirmed using the Cox regression model. RESULTS: A total of 82 patients were included in the study: 42 men and 40 women, the mean age was 59 years old (23-83 years old). Tumors were commonly found in the jejunum (46.3%), ileum (20.7%), and duodenum (32.9%). The median tumor size was 6.0 cm (range: 1.0-15.0 cm). The number of mitoses per one 50 high-power field was used to define the mitotic rates. In our present study, 56 patients presented a mitotic rate ≤5 (68.3%) and 26 patients showed a rate >5 (31.7%) at the time of diagnosis. All patients accepted tumor resection without lymph node resection. The positivity rate was 97.6% for CD117, 96.3% for delay of germination 1, 65.9% for CD34, 6.1% for S-100, and 59.8% for smooth muscle actin using immunohistochemistry. Tumor size, tumor rupture, Ki67 index, mitotic index, and postoperative imatinib were independent prognostic factors for small intestinal GISTs. CONCLUSIONS: In this study, larger tumor size, high Ki67 index, high mitotic index, the occurrence of tumor rupture, and use of imatinib were independent unfavorable prognostic indicators.

[Management and prognosis of acute arterial embolism: a multivariable analysis of 346 patients].

OBJECTIVE: To evaluate the management of acute arterial embolism (AAE) and its prognostic factors. METHODS: The clinical data of 346 AAE patients treated at our hospital between January 1998 and October 2008 were retrospectively reviewed. The prognostic factors, including age, gender, extremities, location of embolism, ischemic duration, ischemic categories, and therapeutic methods, postoperative complications were evaluated by multivariate Logistic regression analysis. RESULTS: There were 210 males and 136 females with a mean age of (63 ± 14) years old. Fifty-six patients occurred in the upper extremities and 290 patients in the lower extremities. The causes included cardiogenic embolism (n = 301), vasogenic embolism (n = 33) and unknown origin (n = 12). The duration of ischemia ranged from 1 h to 7 d. Only 44 patients were admitted ≤ 8 h and the remainder > 8 h. The categories of extremity ischemia were level I (n = 17), level IIA (n = 69), level IIB (n = 221) and level III (n = 39). The procedures included embolectomy (n = 280), interventional thrombolysis (n = 19) and conservative treatment (n = 47). Thirteen patients (3.76%) died of complications during the perioperative periods. And 44 (12.72%) underwent amputations and 289 (83.53%) had excellent clinical outcome with extremity salvage. During a 5-year follow-up period, 38 patients had a recurrent embolism. The Logistic regression analysis showed that ischemic duration, ischemic category, therapeutic methods and complications had significant prognostic influences (all P < 0.05). And other factors such as age, gender, extremities and the location of embolism had insignificant influences (all P > 0.05). CONCLUSION: Embolectomy is the first-choice therapy for AAE with an excellent outcome. Ischemic duration, ischemic grading, surgical treatment and complications have significant prognostic influences. Systematic medical treatments, such as effective anticoagulation, are vital in the prevention of recurrent AAE.

An Update on the Potential Roles of E2F Family Members in Colorectal Cancer.

Colorectal cancer (CRC) is a major health burden worldwide, and thus, optimised diagnosis and treatments are imperative. E2F transcription factors (E2Fs) are a family of transcription factors consisting of eight genes, contributing to the oncogenesis and development of CRC. Importantly, E2Fs control not only the cell cycle but also apoptosis, senescence, DNA damage response, and drug resistance by interacting with multiple signaling pathways. However, the specific functions and intricate machinery of these eight E2Fs in human CRC remain unclear in many respects. Evidence on E2Fs and CRC has been scattered on the related regulatory genes, microRNAs (miRNAs), and competing endogenous RNAs (ceRNAs). Accordingly, some drugs targeting E2Fs have been transferred from preclinical to clinical application. Herein, we have systemically reviewed the current literature on the roles of various E2Fs in CRC with the purpose of providing possible clinical implications for patient diagnosis and prognosis and future treatment strategy design, thereby furthering the understanding of the E2Fs.