Analysis of vascular thrombus and clinicopathological factors in prognosis of gastric cancer: A retrospective cohort study.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in the world, and its prognosis is closely related to many factors. In recent years, the incidence of vascular thrombosis in patients with GC has gradually attracted increasing attention, and studies have shown that it may have a significant impact on the survival rate and prognosis of patients. However, the specific mechanism underlying the association between vascular thrombosis and the prognosis of patients with GC remains unclear. AIM: To analyze the relationships between vascular cancer support and other clinicopathological factors and their influence on the prognosis of patients with GC. METHODS: This study retrospectively analyzed the clinicopathological data of 621 patients with GC and divided them into a positive group and a negative group according to the presence or absence of a vascular thrombus. The difference in the 5-year cumulative survival rate between the two groups was compared, and the relationships between vascular cancer thrombus and other clinicopathological factors and their influence on the prognosis of patients with GC were analyzed. RESULTS: Among 621 patients with GC, the incidence of vascular thrombi was 31.7% (197 patients). Binary logistic regression analysis revealed that the degree of tumor differentiation, depth of invasion, and extent of lymph node metastasis were independent influencing factors for the occurrence of vascular thrombi in GC patients (P < 0.01). The trend of the χ 2 test showed that the degree of differentiation, depth of invasion, and extent of lymph node metastasis were linearly correlated with the percentage of vascular thrombi in GC patients (P < 0.01), and the correlation between lymph node metastasis and vascular thrombi was more significant (r = 0.387). Univariate analysis revealed that the 5-year cumulative survival rate of the positive group was significantly lower than that of the negative group (46.7% vs 73.3%, P < 0.01). Multivariate analysis revealed that age, tumor diameter, TNM stage, and vascular thrombus were independent risk factors for the prognosis of GC patients (all P < 0.05). Further stratified analysis revealed that the 5-year cumulative survival rate of stage III GC patients in the thrombolase-positive group was significantly lower than that in the thrombolase-negative group (36.1% vs 51.4%; P < 0.05). CONCLUSION: Vascular cancer status is an independent risk factor affecting the prognosis of patients with GC. The combination of vascular cancer suppositories and TNM staging can better judge the prognosis of patients with GC and guide more reasonable treatment.

SEfficacy and safety of apatinib in the treatment of patients with platinum­resistant ovarian cancer: A systematic review and network meta­analysis.

At present, the optimal therapeutic approach for the treatment of platinum-resistant recurrent ovarian cancer remains to be fully elucidated. The present systematic review and network meta-analysis aimed to elucidate the relative efficacy and safety of apatinib, administered either as monotherapy or in conjunction with chemotherapy, compared with chemotherapy alone, for the treatment of platinum-resistant recurrent ovarian cancer. The PubMed, Embase and Wanfang Data electronic databases were searched, where the search spanned from the conception of the databases until April 2023. A quality evaluation was conducted and R software was used for network meta-analysis. Following inclusion and exclusion criteria screening, the present analysis included 17 clinical trials, combining data from 1,228 patients with platinum-resistant recurrent ovarian cancer categorized into the following three treatment cohorts: i) 555 patients who received apatinib plus chemotherapy; ii) 229 patients who received apatinib alone; and iii) 444 patients who underwent conventional chemotherapy. Results of the present study demonstrated that the co-administration of apatinib with either tegiol [odds ratio (OR), 2.54; 95% CI, 1.06-6.11] or etoposide (OR, 2.12; 95% CI, 1.20-3.74) significantly improved the objective response rate (ORR) compared with that following apatinib monotherapy. By contrast, gemcitabine monotherapy resulted in inferior ORR efficacy compared with that following apatinib (OR, 0.47; 95% CI, 0.23-0.95). In addition, combinations of apatinib with etoposide (OR, 1.32; 95% CI, 1.06-1.64) or paclitaxel (OR, 1.52; 95% CI, 1.04-2.23) demonstrated a significantly improved disease control rates (DCR) compared with those following apatinib alone. According to the area under the cumulative ranking analysis, apatinib and paclitaxel in combination was the most efficacious treatment modality in terms of DCR. In terms of safety, the incidence of adverse events, such as hand-foot syndrome [relative risk (RR), 4.23; 95% CI, 1.80-9.95] and hypertension (RR, 4.80; 95% CI, 1.53-15.05), was found to be significantly higher in patients treated with apatinib-containing therapies, compared with those treated with chemotherapy alone. Consequently, the present meta-analysis highlighted the potential of apatinib, particularly in combination with chemotherapy, as a therapeutic strategy for patients with platinum-resistant recurrent ovarian cancer.

Occurrence and prevention of incisional hernia following laparoscopic colorectal surgery.

Among minimally invasive surgical procedures, colorectal surgery is associated with a notably higher incidence of incisional hernia (IH), ranging from 1.7% to 24.3%. This complication poses a significant burden on the healthcare system annually, necessitating urgent attention from surgeons. In a study published in the World Journal of Gastrointestinal Surgery, Fan et al compared the incidence of IH among 1614 patients who underwent laparoscopic colorectal surgery with different extraction site locations and evaluated the risk factors associated with its occurrence. This editorial analyzes the current risk factors for IH after laparoscopic colorectal surgery, emphasizing the impact of obesity, surgical site infection, and the choice of incision location on its development. Furthermore, we summarize the currently available preventive measures for IH. Given the low surgical repair rate and high recurrence rate associated with IH, prevention deserves greater research and attention compared to treatment.

Impact of immunotherapy on liver metastasis.

This editorial discusses the article "Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis" published in the latest edition of the World Journal of Gastrointestinal Surgery. Immunotherapy has achieved outstanding success in tumor treatment. However, the presence of liver metastasis (LM) restrains the efficacy of immunotherapy in various tumors, including lung cancer, colorectal cancer, renal cell carcinoma, melanoma, and gastric cancer. A decrease in CD8+ T cells and nature killer cells, along with an increase in macrophages and regulatory T cells, was observed in the microenvironment of LM, leading to immunotherapy resistance. More studies are necessary to determine the best strategy for enhancing the effectiveness of immunotherapy in patients with LM.

Intestinal Behçet's disease: A review of clinical diagnosis and treatment.

Behçet's disease (BD) is a chronic inflammatory disorder prone to frequent recurrences, with a high predilection for intestinal involvement. However, the efficacy and long-term effects of surgical treatment for intestinal BD are unknown. In the current issue of World J Gastrointest Surg, Park et al conducted a retrospective analysis of 31 patients with intestinal BD who received surgical treatment. They found that elevated C-reactive protein levels and emergency surgery were poor prognostic factors for postoperative recurrence, emphasizing the adverse impact of severe inflammation on the prognosis of patients with intestinal BD. This work has clinical significance for evaluating the postoperative condition of intestinal BD. The editorial attempts to summarize the clinical diagnosis and treatment of intestinal BD, focusing on the impact of adverse factors on surgical outcomes. We hope this review will facilitate more precise postoperative management of patients with intestinal BD by clinicians.

Ovatodiolide inhibited hepatocellular carcinoma stemness through SP1/MTDH/STAT3 signaling pathway.

Hepatocellular carcinoma (HCC) is characterized with high recurrence and mortality, and the clinical treatments for HCC are very limited. Hepatocellular carcinoma stem cells are the root of HCC progress, recurrence, and multidrug resistance. Ovatodiolide (OVA) is a bioactive diterpenoid served as an inflammatory and immunotherapeutic responses modulator. In this research, we found OVA inhibited HCC stemness through inhibiting MTDH gene transcription. Moreover, we firstly discovered transcription factor SP1 bound to the promoter region of MTDH to transcriptionally regulate MTDH level. Mechanically, we demonstrated OVA decreased SP1 protein stability to transcriptionally inhibit MTDH gene, and inhibited the nuclear translocation of p65, and then diminished IL-6 level to suppress JAK/STAT3 signaling pathway, eventually decreases CD133 level and the stemness of HCC. Furthermore, we demonstrated ACT004, OVA derivative with high metabolic stability towards cytochrome P450 enzymes, showed no genotoxicity and no accumulative or delayed toxicities after long-term administration in rats. And the in vivo efficacy experiments indicated ACT004 inhibited tumor growth of hepatocellular carcinoma. In conclusion, we revealed the mechanism of OVA in regulating HCC stemness, detected the toxicity of OVA derivative and evaluated the in vivo efficacy which lays a foundation for further discovery of anti-HCC stem cell agents and provide a new strategy for the application of OVA in clinical treatment.

Relationship between Helicobacter pylori infection and colorectal polyp/colorectal cancer.

Helicobacter pylori (H. pylori) plays an important role in the development of gastric cancer, although its association to colorectal polyp (CP) or colorectal cancer (CRC) is unknown. In this issue of World Journal of Gastrointestinal Surgery, Zhang et al investigated the risk factors for H. pylori infection after colon polyp resection. Importantly, the researchers used R software to create a prediction model for H. pylori infection based on their findings. This editorial gives an overview of the association between H. pylori and CP/CRC, including the clinical significance of H. pylori as an independent risk factor for CP/CRC, the underlying processes of H. pylori-associated carcinogenesis, and the possible risk factors and identification of H. pylori.

Is there a place for endoscopic management in post-cholecystectomy iatrogenic bile duct injuries?

In this editorial we comment on the article by Emara et al published in the recent issue of the World Journal of Gastrointestinal Surgery. Previously, surgery was the primary treatment for bile duct injuries (BDI). The treatment of BDI has advanced due to technological breakthroughs and minimally invasive procedures. Endoscopic and percutaneous treatments have largely supplanted surgery as the primary treatment for most instances in recent years. Patient management, including the specific technique, is typically impacted by local knowledge and the kind and severity of the injury. Endoscopic therapy is a highly successful treatment for postoperative benign bile duct stenosis and offers superior long-term outcomes compared to surgical correction. Based on the damage features of BDI, therapeutic options include endoscopic duodenal papillary sphincterotomy, endoscopic nasobiliary drainage, and endoscopic biliary stent implantation.

Mutational landscape of TP53 and CDH1 in gastric cancer.

In this editorial we comment on an article published in a recent issue of the World J Gastrointest Surg. A common gene mutation in gastric cancer (GC) is the TP53 mutation. As a tumor suppressor gene, TP53 is implicated in more than half of all tumor occurrences. TP53 gene mutations in GC tissue may be related with clinical pathological aspects. The TP53 mutation arose late in the progression of GC and aided in the final switch to malignancy. CDH1 encodes E-cadherin, which is involved in cell-to-cell adhesion, epithelial structure maintenance, cell polarity, differentiation, and intracellular signaling pathway modulation. CDH1 mutations and functional loss can result in diffuse GC, and CDH1 mutations can serve as independent prognostic indicators for poor prognosis. GC patients can benefit from genetic counseling and testing for CDH1 mutations. Demethylation therapy may assist to postpone the onset and progression of GC. The investigation of TP53 and CDH1 gene mutations in GC allows for the investigation of the relationship between these two gene mutations, as well as providing some basis for evaluating the prognosis of GC patients.

Overview of ectopic pancreas.

This editorial discusses the article written by Zheng et al that was published in the latest edition of the World Journal of Gastrointestinal Surgery. Our primary focus is on the causes, location, diagnosis, histological classification, and therapy of ectopic pancreas. Ectopic pancreas refers to the presence of pancreatic tissue that is situated in a location outside its usual anatomical placement, and is not connected to the normal pancreas in terms of blood supply or anatomical structure. Currently, the embryological origin of ectopic pancreas remains uncertain. The most prevalent form of ectopic pancreatic is gastric ectopic pancreas. Endoscopic ultrasonography examination can visualize the morphological characteristics of the ectopic pancreatic lesion and pinpoint its anatomical location. The histological categorization of ectopic pancreas evolves. Endoscopic treatment has been widely advocated in ectopic pancreas.

Preliminary application of real-time shear wave elastography to evaluate endometrial receptivity and predict pregnancy outcome.

BACKGROUND: Endometrial receptivity is crucial for the establishment of a healthy pregnancy outcome. Previous research on endometrial receptivity primarily examined endometrial thickness, endometrial echo types, and endometrial blood supply. OBJECTIVE: To explore the differences in the elastic modulus of the endometrium in women with various pregnancy outcomes by real-time shear wave elastography (SWE) and to investigate its application value in evaluation of endometrial receptivity. METHODS: A total of 205 pregnant women who were admitted at Wenzhou People's Hospital between January 2021 and December 2022 were selected. Three-dimensional transvaginal sonography and real-time shear wave elastography were performed in the proliferative phase and receptive phase of the endometrium, and the average elastic modulus of the endometrium in the two phases was obtained and compared. According to whether the pregnancy was successful or not, the participants were divided into the pregnancy group (n= 72) and non-pregnancy group (n= 133), and the differences in intimal thickness, 3D blood flow parameters, and average elastic modulus of intima were compared between the two groups. RESULTS: The average elastic modulus of the endometrium in the proliferative phase and receptive phase was (23.92 ± 2.31) kPa and (11.82 ± 2.24) kPa, respectively, and the difference was statistically significant P< 0.05. The average elastic modulus of the endometrium in the pregnancy group and non-pregnancy group was (9.97 ± 1.08) kPa and (12.82 ± 2.06) kPa, respectively, and the difference was statistically significant P< 0.05. The area under the curve of predicting pregnancy by the average elastic modulus of the endometrium in the receptive phase was 0.888 (0.841∼0.934), with corresponding P value < 0.05. The critical value was 11.15, with a corresponding sensitivity of 81.7% and specificity of 78.2%. CONCLUSION: Real-time shear wave elastography can quantitatively evaluate endometrial elasticity, indirectly reflect the endometrial phase, and provide a new diagnostic concept for evaluating endometrial receptivity and predicting pregnancy outcome in infertile patients.

Sulfated Chitosan Nanofibrous Scaffolds Seeded With Adipose Stem Cells Promote Ischemic Wound Healing in a Proangiogenic Strategy.

Ischemic wounds are chronic wounds with poor blood supply that delays wound reconstruction. To accelerate wound healing and promote angiogenesis, adipose-derived stem cells (ADSCs) are ideal seed cells for stem cell-based therapies. Nevertheless, providing a favorable environment for cell proliferation and metabolism poses a substantial challenge. A highly sulfated heparin-like polysaccharide 2-N, 6-O-sulfated chitosan (26SCS)-doped poly(lactic-co-glycolic acid) scaffold (S-PLGA) can be used due to their biocompatibility, mechanical properties, and coagent 26SCS high affinity for growth factors. In this study, a nano-scaffold system, constructed from ADSCs seeded on electrospun fibers of modified PLGA, was designed to promote ischemic wound healing. The S-PLGA nanofiber membrane loaded with adipose stem cells ADSCs@S-PLGA was prepared by a co-culture in vitro, and the adhesion and compatibility of cells on the nano-scaffolds were explored. Scanning electron microscopy was used to observe the growth state and morphological changes of ADSCs after co-culture with PLGA electrospun fibers. The proliferation and apoptosis after co-culture were detected using a Cell Counting Kit-8 kit and flow cytometry, respectively. An ischemic wound model was then established, and we further studied the ability of ADSCs@S-PLGA to promote wound healing and angiogenesis. We successfully established ischemic wounds on the backs of rats and demonstrated that electrospun fibers combined with the biological effects of adipose stem cells effectively promoted wound healing and the growth of microvessels around the ischemic wounds. Phased research results can provide a theoretical and experimental basis for a new method for promoting clinical ischemic wound healing.

Radiomic features of the hippocampal based on magnetic resonance imaging in the menopausal mouse model linked to neuronal damage and cognitive deficits.

Estrogen deficiency in the early postmenopausal phase is associated with an increased long-term risk of cognitive decline or dementia. Non-invasive characterization of the pathological features of the pathological hallmarks in the brain associated with postmenopausal women (PMW) could enhance patient management and the development of therapeutic strategies. Radiomics is a means to quantify the radiographic phenotype of a diseased tissue via the high-throughput extraction and mining of quantitative features from images acquired from modalities such as CT and magnetic resonance imaging (MRI). This study set out to explore the correlation between radiomics features based on MRI and pathological features of the hippocampus and cognitive function in the PMW mouse model. Ovariectomized (OVX) mice were used as PWM models. MRI scans were performed two months after surgery. The brain's hippocampal region was manually annotated, and the radiomic features were extracted with PyRadiomics. Chemiluminescence was used to evaluate the peripheral blood estrogen level of mice, and the Morris water maze test was used to evaluate the cognitive ability of mice. Nissl staining and immunofluorescence were used to quantify neuronal damage and COX1 expression in brain sections of mice. The OVX mice exhibited marked cognitive decline, brain neuronal damage, and increased expression of mitochondrial complex IV subunit COX1, which are pathological phenomena commonly observed in the brains of AD patients, and these phenotypes were significantly correlated with radiomics features (p < 0.05, |r|>0.5), including Original_firstorder_Interquartile Range, Original_glcm_Difference Average, Original_glcm_Difference Average and Wavelet-LHH_glszm_Small Area Emphasis. Meanwhile, the above radiomics features were significantly different between the sham-operated and OVX groups (p < 0.01) and were associated with decreased serum estrogen levels (p < 0.05, |r|>0.5). This initial study indicates that the above radiomics features may have a role in the assessment of the pathology of brain damage caused by estrogen deficiency using routinely acquired structural MR images.

Systems genetics and bioinformatics analyses using ESR1-correlated genes identify potential candidates underlying female bone development.

Estrogen receptor α (ESR1) is involved in E2 signaling and plays a major role in postmenopausal bone loss. However, the molecular network underlying ESR1 has not been explored. We used systems genetics and bioinformatics to identify important genes associated with Esr1 in postmenopausal bone loss. We identified ~2300 Esr1-coexpressed genes in female BXD bone femur, functional analysis of which revealed 'osteoblast signaling' as the most enriched pathway. PPI network led to the identification of 25 'female bone candidates'. The gene-regulatory analysis revealed RUNX2 as a key TF. ANKRD1 and RUNX2 were significantly different between osteoporosis patients and healthy controls. Sp7, Col1a1 and Pth1r correlated with multiple femur bone phenotypes in BXD mice. miR-3121-3p targeted Csf1, Ankrd1, Sp7 and Runx2. ß-estradiol treatment markedly increased the expression of these candidates in mouse osteoblast. Our study revealed that Esr1-correlated genes Ankrd1, Runx2, Csf1 and Sp7 may play important roles in female bone development.

Effect of SARS-CoV-2 Breakthrough Infection on HIV Reservoirs and T-Cell Immune Recovery in 3-Dose Vaccinated People Living with HIV.

People living with human immunodeficiency virus (PLWH) are a vulnerable population with a higher risk of severe coronavirus disease 2019 (COVID-19); therefore, vaccination is recommended as a priority. Data on viral reservoirs and immunologic outcomes for PLWH breakthrough infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently limited. In this study, we investigated the effects of SARS-CoV-2 breakthrough infection on hematological parameters, human immunodeficiency virus (HIV) reservoir size, and T-cell recovery in PLWH receiving antiretroviral therapy (ART) after SARS-CoV-2 booster vaccination. The results indicated that during breakthrough infection, booster vaccination with homologous and heterologous vaccines was safe in PLWH after receiving two doses of inactivated vaccination. The absolute CD4 counts decreased in the heterologous group, whereas the CD8 counts decreased in the homologous booster group after breakthrough infection in PLWH. Breakthrough infection increased HIV reservoirs and was associated with increased T-cell activation in PLWH who received virally suppressed ART and a 3-dose vaccination. According to our data, the breakthrough infection of SARS-CoV-2 may put PLWH at a greater risk for increased HIV reservoirs, even if these individuals were virally suppressed with ART after 3-dose SARS-CoV-2 vaccination.

DNA methylation: The epigenetic mechanism of Alzheimer's disease.

Nowadays, with the development of the social health care system, there is an increasing trend towards an aging society. The incidence of Alzheimer's disease (AD) is also on the rise. AD is a kind of neurodegenerative disease that can be found in any age group. For years, scientists have been committing to discovering the cause of AD. DNA methylation is one of the most common epigenetic mechanisms in mammals and plays a vital role in the pathogenesis of several diseases, including tumors. Studying chemical changes in the epigenome, or DNA methylation can help us understand the effects of our environment and life on diseases, such as smoking, depression, and menopause, which may affect people's chances of developing Alzheimer's or other diseases. Recent studies have identified some crucial genes like ANK1, RHBDF2, ABCA7, and BIN1, linking DNA methylation to AD. This review focuses on elucidating the relationship between DNA methylation and the pathogenesis of AD and provides an outlook on possible targeted therapeutic modalities.

Differential gene expression between wild-type and Gulo-deficient mice supplied with vitamin C

The aim of this study was to test the hypothesis that hepatic vitamin C (VC) levels in VC deficient mice rescued with high doses of VC supplements still do not reach the optimal levels present in wild-type mice. For this, we used a mouse scurvy model (sfx) in which the L-gulonolactone oxidase gene (Gulo) is deleted. Six age- (6 weeks old) and gender- (female) matched wild-type (WT) and sfx mice (rescued by administering 500 mg of VC/L) were used as the control (WT) and treatment (MT) groups (n = 3 for each group), respectively. Total hepatic RNA was used in triplicate microarray assays for each group. EDGE software was used to identify differentially expressed genes and transcriptomic analysis was used to assess the potential genetic regulation of Gulo gene expression. Hepatic VC concentrations in MT mice were significantly lower than in WT mice, even though there were no morphological differences between the two groups. In MT mice, 269 differentially expressed transcripts were detected (> twice the difference between MT and WT mice), including 107 up-regulated and 162 down-regulated genes. These differentially expressed genes included stress-related and exclusively/predominantly hepatocyte genes. Transcriptomic analysis identified a major locus on chromosome 18 that regulates Gulo expression. Since three relevant oxidative genes are located within the critical region of this locus we suspect that they are involved in the down-regulation of oxidative activity in sfx mice.

Evaluation of gene expression profiling in a mouse model of L-gulonolactone oxidase gene deficiency

Humans and guinea pigs are species which are unable to synthesize ascorbic acid (vitamin C) because, unlike rodents, they lack the enzyme L-gulonolactone oxidase (Gulo). Although the phenotype of lacking vitamin C in humans, named scurvy, has long been well known, information on the impact of lacking Gulo on the gene expression profiles of different tissues is still missing. This knowledge could improve our understanding of molecular pathways in which Gulo may be involved. Recently, we discovered a deletion that includes all 12 exons in the gene for Gulo in the sfx mouse, characterized by spontaneous bone fractures. We report here the initial analysis of the impact of the Gulo gene deletion on the murine gene expression profiles in the liver, femur and kidney.