ABSTRACT Background Colorectal cancer (CRC) is a major public health burden in Hainan Province due to its high incidence and mortality, yet region‐specific prognostic data are lacking. This study evaluates prognostic factors in postsurgical CRC patients to guide localized prevention and treatment. Methods We conducted a retrospective cohort study of 265 patients undergoing first‐time surgery for CRC between January 2015 and December 2021. Kaplan–Meier estimator and log‐rank tests were performed to analyze the overall survival rates of CRC patients. Cox proportional hazards regression and the SHAP method were performed to determine the prognostic factors of CRC. Results The study included 265 patients (mean age 63 ± 12.99 years), with 171 survivors (64.5%) and 94 deaths (35.5%). The 1‐, 3‐ and 5‐year overall survival rates of CRC patients were 93.0%, 82.1%, and 73.9%, respectively, from 2015 to 2021. In multivariable analysis, factors associated with increased mortality risk included advanced age (per 1 year increase: HR = 1.043, 95% CI: 1.018–1.069, p = 0.001), TNM stage III (HR = 11.46, 95% CI: 2.611–50.31, p = 0.001) and stage IV (HR = 15.06, 95% CI: 3.131–72.46, p = 0.001), increased tumor size (per 1 cm increase: HR = 1.267, 95% CI: 1.058–1.519, p = 0.01), positive vascular infiltration (HR = 2.399, 95% CI: 1.162–4.951, p = 0.018), elevated CEA levels (per 1 ng/mL increase: HR = 1.035, 95% CI: 1.012–1.059, p = 0.003), and increased CA125 levels (per 1 U/mL increase: HR = 1.013, 95% CI: 1.003–1.024, p = 0.014), while normal‐weight (HR = 0.385, 95% CI: 0.168–0.880, p = 0.024) was associated with a better survival. No association was found between the expression of MSH2, MDR1, and GSTπ and the survival of the patients. The SHAP beeswarm plot highlighted TNM stage and age as the primary contributors to the model's predictions. Conclusion Increased age, advanced TNM stage, larger tumor size, vascular invasion, and elevated CEA/CA125 were linked to poorer CRC prognosis, while normal BMI was protective. Further prospective studies are needed for validation.

Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-performance liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization, phenol-sulfuric acid assay, and gel permeation chromatography. HT-29 cells were stimulated with lipopolysaccharide and then treated with pectic polysaccharides; conditioned medium was applied to THP-1-derived macrophages to assess cell viability and polarization, while tight junction protein expression was analyzed in HT-29 cells. Furthermore, a mouse model of dextran sulfate sodium-induced colitis was treated with oral pectic polysaccharides or NOS2 overexpression. Body weight, disease activity index, colon length, histopathology, and the protein expression related to the JAK2/STAT3-NOS2 signaling were evaluated.Results:The pectic polysaccharide was characterized as an acidic pectic polysaccharide, primarily composed of galacturonic acid and various neutral sugars, with a narrow molecular weight distribution and high purity. Pectic polysaccharides significantly enhanced THP-1 macrophage viability, promoted M1 to M2 polarization, and upregulated the expression of epithelial tight junction proteins. In addition, pectic polysaccharide treatment attenuated body weight loss, lowered disease activity index scores and improved colon histology in mice with dextran sulfate sodium-induced colitis. It also reduced JAK2/STAT3 phosphorylation and NOS2 expression, and increased the expression of tight junction proteins (ZO-1, occludin, and claudin-1).Conclusions:Pectic polysaccharides attenuate ulcerative colitis by increasing M2-related macrophage markers, inhibiting the JAK2/ STAT3-NOS2 signaling, and enhancing epithelial barrier-related protein expression. These findings support pectic polysaccharides as a natural candidate for the treatment of ulcerative colitis.

Introduction: To investigate the expression and treatment of chemokine CXCL12 and its receptor CXCR4/ CXCR7. Methods: The liver cirrhosis hypersplenism model of rats was made with CCL4, and then was detected by immunohistochemistry, Western blot and qRT-PCR. Results: The area of spleen fibrosis in the model group was significantly larger than that in the control group (p < 0.01), and the expression of CXCL12, CXCR4 and CXCR7 in the model group was significantly higher than that in the control group (p < 0.01). Conclusions: CXCL12-CXCR4/CXCR7 is abnormally high in splenic fibrosis, and blocking its high expression can slow down the occurrence of hypersplenism.

通过对天丝短切纤维进行打浆处理,获得了具有不同原纤化程度的天丝纤维,并结合湿法成形技术制备得到原纤化天丝隔膜.探究了纤维几何尺寸和形貌对隔膜孔隙结构的影响,对不同孔隙结构隔膜制备的超级电容器电化学性能进行了分析.结果表明,天丝纤维经过不同打浆转数处理后,纤维尺寸和隔膜孔隙结构发生了明显变化.随着打浆转数的增加(20000～250000转),粗纤维比例显著降低,质均纤维长度从2.29 mm降至0.76 mm.孔隙率从81.2％降至66.3％,隔膜平均孔径从1.20μm降至0.27μm,隔膜厚度从47.7μm降至26.0μm,但不同原纤化天丝隔膜制备的超级电容器的阻抗、比容量、能量密度和功率密度变化并不明显.

Objective The clinical characteristics and imaging information of insular glioma patients were collected to predict mutation status of isocitrate dehydrogenase 1 (IDH1). Methods A total of 596 patients with gliomas confirmed by postoperative pathology in The First Affiliated Hospital with Nanjing Medical University from January 2011 to June 2021 were enrolled, including 72 insular gliomas, 213 frontal gliomas, 165 temporal gliomas, 76 parietal gliomas, 28 and 29 midline gliomas. All patients were examined by MRI, fifteen glioma⁃related features were selected from the visually accessible rembrandt images (VASARI), including enhancement quality, enhancement proportion, non⁃enhancement proportion, necrosis proportion, edema proportion, cyst, thickness of enhanced margin, definition of the enhanced margin, hemorrhage, diffusion, deep white matter involvement, deep ventricle involvement, midline cross, T2⁃FLAIR mismatch, maximum diameter of tumor. Univariate and multivariate Logistic regression analysis were used to screen the predictive factors related to IDH1⁃mutant in insular glioma. The receiver operating characteristic (ROC) curve was plotted and area under the curve (AUC), sensitivity and specificity were calculated to evaluate the predictive power of MRI features for IDH1⁃mutant glioma. Results IDH1 mutation rate was higher in insular and frontal gliomas (P＜0.01, for all). WHO grade Ⅱ had the highest IDH1 mutation rate (P=0.008, 0.000), and grade Ⅳ had the lowest mutation rate (P=0.000). The IDH1 mutation rate in low⁃expression Ki⁃67 gliomas was higher than that in high⁃expression gliomas (P=0.000). Logistic regression analysis showed that weak enhancement (OR=35.671, 95%CI: 2.805-453.600; P=0.006), non⁃enhancement (OR=75.453, 95%CI: 2.881-1872.759; P=0.009), unlimited diffusion (OR=10.573, 95%CI: 1.043-107.175; P=0.046), no deep ventricle involvement (OR=187.601, 95%CI: 2.269-15507.607; P=0.020), T2⁃FLAIR mismatch (OR=47.536, 95%CI: 2.838-796.097; P=0.007) were independent predictive factors for IDH1 mutation in insular glioma. The AUC of enhancement degree, diffusion, deep ventricle involvement and T2⁃FLAIR mismatch for the diagnosis of IDH1⁃mutant glioma were 0.846 (95%CI: 0.748-0.944, P=0.000), 0.730 (95%CI: 0.609-0.850, P=0.001), 0.708 (95%CI: 0.584-0.833, P=0.003) and 0.745 (95%CI: 0.627-0.864, P=0.000). The combination of the 4 groups had the highest diagnostic efficacy, and the AUC was 0.961 (95%CI: 0.923-0.999, P=0.000). Conclusions Low grade insular glioma has a high IDH1 mutation rate. MRI features of weak enhancement and non⁃enhancement, unlimited diffusion, non deep ventricle involvement and T2⁃FLAIR mismatch contribute to noninvasive prediction of IDH1⁃mutant insular glioma.

Colorectal cancer (CRC) is a malignant tumor with a high incidence and mortality worldwide. Currently, the underlying molecular mechanisms of CRC are still unclear. Zinc finger protein 3 (ZNF3) is a zinc-finger transcription factor that has been reported as a candidate for breast cancer prognosis, suggesting its involvement in the regulation of tumorigenesis. However, the association between ZNF3 and CRC remains unknown. To investigate the role of ZNF3 in CRC, we first analyze the correlation between ZNF3 expression and CRC, and the results demonstrate that ZNF3 is highly expressed in CRC tissue and cells, which is associated with the age of CRC patients. In vitro studies show that ZNF3 overexpression promotes CRC cell migration. Compared to control cells, knockdown of ZNF3 markedly suppresses CRC cell proliferation, migration and invasion and promotes G0/G1 phase cell cycle arrest. The expressions of the EMT-related markers TWIST and MMP1 are significantly decreased when ZNF3 is silenced. Additionally, overexpression of MMP1 and TWIST exacerbates CRC cell proliferation, accelerates the S phase cell cycle in ZNF3-knockdown SW480 cells, and increases cell migration and invasion through Transwell chambers. These data suggest that ZNF3 is involved in cellular proliferation, migration and invasion by regulating MMP1 and TWIST in CRC cells.

Abstract BackgroundNeurosurgeons are increasingly capable of maintaining language and motor functions in glioma patients following surgery due to the ability to preserve traditionally “eloquent” structures. However, glioma patients continue to present with severe morbidity in cognitive functions due to the lack of familiarity in the neurosurgical community with non-traditionally “eloquent” brain networks. Therefore, the authors sought to identify and describe the frequency of invasion and/or proximity of Insulo-Sylvian gliomas to portions of non-traditional, large scale brain networks during surgery.MethodsA retrospective analysis was completed of consecutive adult patients undergoing surgery for newly diagnosed glioma at a single center between 2017-2020 with WHO grade II-IV infiltrating gliomas centered in the insula, opercular cortices or temporal stem. Diffusion tensor imaging (DTI)-based tractography was completed by creating a personalized brain connectome atlas based on the Human Connectome parcellation scheme with Quicktome software. This algorithm utilizes an machine learning (ML)-approach to assign voxels of the cerebral cortex to various brain regions according to structural connectivity patterns of voxels in the brain region of interest utilizing neuroimaging data specifically from normal healthy adults. Insulo-Sylvian tumors were categorized based on their involvement with non-traditional cognitive networks versus traditionally eloquent structures.Results45 patients were included (47±15 years, 51% female) consisting of mostly high grade (IV)-gliomas (56%) compared WHO grade II (22%) or III (22% tumors). Ultimately, 44/45 (98%) patients demonstrated tumor involvement (<1cm proximity or invasion) to the cortical or subcortical components of a non-traditional, large scale brain network or major white matter pathway involved in cognition. In comparison, 35/45 (78%) patients demonstrated tumor involvement of traditionally considered “eloquent” structures like the corticospinal tract or language regions/tracts. The most common non-traditional cognitive networks involved in cases included the salience network (60%) followed by the central executive network (56%). ConclusionsNon-traditionally “eloquent” brain networks are increasingly encountered during surgical resection of Insulo-Sylvian gliomas in both hemispheres and must be considered moving forward. Damage or dysfunction in these networks has been shown to result in severe cognitive morbidity and an improved understanding of their presence can allow for more informed surgical decisions based on patient onco-functional goals.

Ganoderma mushrooms have been used to treat rheumatoid arthritis (RA) in East Asia. Whether Ganoderic acid A (GAA), the natural product extracted from Ganoderma, could be utilized to alleviate osteoarthritis (OA) is investigated in this study. Destabilization of the medial meniscus (DMM) model was constructed to reveal the in vivo effect of GAA. We found that GAA could significantly alleviate the pathology of DMM, as confirmed by the diminished maximum histologic scores. On the contrary, GAA could down-regulate the relative expression of osteoprotegerin (OPG) and up-regulate the relative expression of nuclear factor kappa-B ligand (RANKL) in DMM cartilage and human articular chondrocytes (HC-A) cells with diminished matrix metallopeptidase 13 (MMP-13) secretion in the synovial fluid. It was further demonstrated that the serum concentration of OPG was correlated with the severity of osteoarthritis. All these data reveal that GAA could improve OA by regulating the RANKL/OPG ratio to inhibit the secretion of MMP-13.

Human gastric cancer is a leading cause of cancer mortality in the world wide. We found that the expression of IL-17a was significantly increased in gastric cancer cells. Treatment with recombinant IL-17a (rIL-17a) can increase migration, invasion and epithelial to mesenchymal transition (EMT) of gastric cancer cells. Further, Snail, a key factor to regulate EMT, was significantly increased in rIL-17a-treated gastric cancer cells. While knockdown of Snail can abolish IL-17a-induced EMT of gastric cancer cells. Mechanistically, IL-17a can promote the translation efficiency of Snail, while had no effect on its mRNA expression or protein stability. Further, we found that IL-17a can increase the expression of HuR, which markedly promoted translation of Snail mRNA. While knockdown of HuR can reverse rIL-17a-induced expression of Snail and EMT of gastric cancer cells. Collectively, our data suggested that HuR confers IL-17a induced migration and invasion of gastric cancer cells via upregulation of Snail translation.

The aim of this study was to investigate the effect of circSnap47 on heart failure (HF) and its potential mechanisms. Quantitative real-time PCR (qRT-PCR) was performed to detect the mRNA expression levels of circSnap47 and miR-233-3p. The viability and apoptosis of H9C2 cells were assessed using CCK-8 and TUNEL assays. The expressions of interleukin (IL)-6, IL-1β, IL-18, and tumor necrosis factor-alpha were determined using ELISA and qRT-PCR. In addition, the expression of apoptosis-related proteins and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins was analyzed using western blot. Moreover, HF-related circRNAs and miRNAs were predicted via bioinformatics analysis. The relationship between circSnap47 and miR-233-3p was further confirmed using a dual-luciferase reporter gene assay. In HF tissues and H9C2 cells treated with oxygen–glucose deprivation (OGD), circSnap47 was upregulated. Silencing circSnap47 increased cell viability and inhibited apoptosis. Besides, silencing circSnap47 alleviated OGD-induced inflammation in H9C2 cells. Moreover, we found that miR-233-3p was the downstream target gene of circSnap47. Our results also revealed that silencing circSnap47 relieved OGD-induced H9C2 cell damage by inactivating the miR-223-3p/MAPK axis. We confirmed that circSnap47 silencing inhibited HF progression via regulation of miR-223/MAPK axis, which will provide for a new therapeutic direction for the treatment of HF.

目的 探究儿童主动脉瓣单叶置换(single aortic valve replacement,SAVR)术后主动脉瓣关闭不全(aortic insufficiency,AI)的生物力学机制,并提出应对措施.方法 构建理想化主动脉瓣模型及术后生长模型.改变置换瓣叶游离缘长度、瓣叶高度以及改进设计的一种凹型结构,比较不同结构尺寸对术后主动脉瓣运动同步性和关闭性能的影响.结果 置换瓣叶的闭合滞后于自体瓣叶,自体瓣叶贴合于置换瓣叶游离缘下方2 mm处.术后6年出现明显AI.增加瓣叶高度不能改善术后效果,且会增加瓣叶的最大应力.增加游离缘长度10％能够改善术后效果,当游离缘增加15％,会造成主动脉瓣过长,导致主动脉瓣产生不良的贴合.凹型主动脉瓣较传统结构更有利于瓣叶对合,能够有效降低最大应力20％,效果最佳.结论 儿童行SAVR术后,会使瓣叶运动不同步,对合点发生偏移,术后6年出现AI现象.建议裁剪为增加游离缘长度10％的凹型结构,不建议增加瓣叶高度.

*These authors contributed equally to this work Background: Increasing evidence shows that circular RNAs (circRNAs) play a key role in the development of colorectal cancer (CRC). An interesting candidate RNA in this context is hsa-circRNA-0067835 (circIFT80), but its network of actions is still unclear. Methods: Big data mining technology was used to explore the downstream microRNAs (miRNA) and messenger RNAs (mRNA) of the circIFT80 network. A regulatory network, comprising circIFT80 and its corresponding miRNAs and mRNAs, was derived to preliminarily explore the potential mechanism of circIFT80 in CRC. Finally, the proposed regulatory network was experimentally verified at the cellular level. Results: A total of 6 miRNAs were screened, of which hsa-miR-197-3p, hsa-miR-370-3p and hsa-miR-377-5p may be the most potential downstream miRNAs of hsa-circRNA -0067835 in CRC. A total of 74 up-regulated genes with opposite miRNA expression were selected for subsequent verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases revealed that the target genes occurred more frequently in cancer-related pathways. In addition, protein–protein interaction (PPI) analysis of the target genes revealed a set of involved genes from which the hubTop 10 genes were selected for further analysis. Moreover, circRNA-miRNA-hubTop 10 mRNA networks were constructed. According to this analysis, circIFT80 simultaneously regulates hsa-miR-197-3p, hsa-miR -370-3p, and hsa-miR-377-5p, among which hsa-miR-370-3p seems to be associated with further genes that may be relevant to CRC development. Therefore, the proposed circIFT80/ hsa-miR-370-3p/WNT7B, SLC1A5, RCBTB1 and COL6A6 signal axes were subjected to experimental verification. It could be shown that circIFT80 was up-regulated in CRC tissues. The circIFT80 was able to inhibit apoptosis and promote proliferation, migration and invasion. Moreover, circIFT80 inhibited the expression of hsa-miR-370-3p and promoted the expression of COL6A6, RCBTB1, SLC1A5 and WNT7B in CRC cell lines. Dual luciferase reporter assays further validated that circIFT80 is able to bind to hsa-miR-3703p which in turn targets WNT7B. Conclusion: The circIFT80 may play a role in carcinogenesis through the new circIFT80/ hsa-miR-370-3p/WNT7B signal axis. These findings may provide potential biomarkers and therapeutic targets for the treatment of CRC.

This paper concentrates on discussing the properties of Riemann–Liouvile fractional (RLF) calculus of two special continuous functions. The first type proves the non-differentiability of a special continuous function that does not satisfy Hölder condition, and the second type uses fractal iteration to construct a fractal function defined on [Formula: see text] with unbounded variation. Then we calculate RLF integral and RLF derivative of this special function, and give the corresponding numerical calculation results and the corresponding function image.

[目的]评价Xpert MTB/RIF指导的个体化化疗治疗耐利福平/耐多药脊柱结核的初步临床疗效.[方法]回顾分析2017年6月～2018年6月120例接受手术治疗的脊柱结核患者,术后参照既往抗结核化疗史及Xpert MTB/RIF检测结果,制定个体化化疗方案,待表型药敏结果回示后根据药敏结果再次调整化疗方案.[结果]120例患者中,Xpert MTB/RIF检测结核分枝杆菌阳性79例(65.83％),BACTECMGIT960系统培养阳性48例(40.00％),差异具有统计学意义(P＜0.05).Xpert MTB/RIF检出11例发生rpoB基因突变,其中6例表型药敏证明利福平耐药,但1例Xpert MTB/RIF检测阴性患者表型药敏证明利福平耐药.术后各随访时间点,11例患者的红细胞沉降率、C反应蛋白逐渐下降至正常水平.3例出现肝功能损害,5例出现高尿酸血症,对症治疗后上述指标均恢复正常.末次随访骨融合良好,平均融合时间(5.66±2.57)个月.无窦道、冷脓肿、内固定失效、假关节形成等并发症.[结论]基于XpertMTB/RIF指导的个体化化疗方案有利于尽早治愈耐利福平/耐多药脊柱结核,避免治疗失败及其他严重并发症.

Secondary intra- and extrahepatic bile duct dilatation is a very common condition that can be caused by several diseases. However, it has been rarely discussed in the specialized literature. Moreover, no distinct etiology can be determined in some cases, which hampers the diagnosis and treatment. Here, we discuss the etiological classification and treatment strategies of secondary intra- and extrahepatic bile duct dilatation based on an extensive literature review, as well as our experimental research and clinical experience. The etiology of secondary intra- and extrahepatic bile duct dilatation can be classified in different ways. From a clinicopathological perspective, it can be classified into obstruction-, lesion-, and compression-induced dilatation. Treatment varies depending on the cause. For example, endoscopic dilation or stenting is used for biliary strictures, laparoscopic choledochectomy for stone removal, and resection for cholangiocarcinoma.

Objectives To evaluate the Th1/Th2 cell profile in spleens of cirrhotic and hypersplenic rats by investigating the expression of Th1-associated chemokine receptors CXCR3, CCR5 and Th2-associated chemokine receptor CCR3. Methods Experimental liver cirrhosis and hypersplenism were induced in rats by the intragastric administration of carbon tetrachloride (CCl4; 40% solution [0.3 ml/100g, twice/week for 8 weeks]) and confirmed by pathology and hemogram. Presence of the three chemokine receptors was investigated by real-time polymerase chain reaction (RT-PCR), immunohistochemical staining, and western blot analysis. Results By comparison with control animals (n=10), RT-PCR demonstrated that CXCR3 and CCR5-mRNA levels were significantly elevated in the hypersplenic rats (n=26) and CCR3-mRNA levels were lower. Immunohistochemical staining showed that by comparison with controls, the mean density of the Th1-associated CXCR3 and CCR5 receptors was significantly increased but there was no difference between groups in Th2-associated CCR3 receptors. Western blot analysis showed that by comparison with controls, hypersplenic rats had higher levels of CXCR3 and CCR5 protein but lower levels of CCR3 protein. Conclusions The abnormal expression of Th1-associated chemokine receptors in spleens of rats with cirrhosis and hypersplenism induced by CCL4 suggests that a functional imbalance between Th1/Th2 cells may play a role in the pathogenesis of hypersplenism.

Melanoma is a common solid malignant tumor with a high frequency of metastasis and relapse. Evodiamine (EVO), a natural small molecule, has recently attracted considerable attention due to its pharmacological action, including its anticancer effects. However, the mechanism of the cytotoxic effect exerted by EVO on tumor cells is not yet fully understood. The present study aimed to evaluate the antitumor effects of evodiamine in human melanoma A-375 cells. The results demonstrated that EVO inhibited cell proliferation and induced cell cycle arrest at the G(2)/M stage in human melanoma A-375 cells. The results also revealed that EVO exposure induced the activation of caspase-3, caspase-9 and poly (ADP-ribose) polymerase 1, as well as mitochondrial membrane potential dissipation in a time-dependent manner, indicating that EVO induced intrinsic apoptosis in A-375 cells. Furthermore, the results revealed that receptor-interacting serine/threonine kinase (RIP) and RIP3 were sequentially activated, suggesting that necroptosis may also be involved in EVO-induced cell death in A-375 cells. In addition, co-treatment with catalase was demonstrated to significantly attenuate the EVO-induced cell death in A-375 cells, indicating that reactive oxygen species (ROS) may serve an important role in EVO-induced cell death. In conclusion, the results of the present study unveiled a novel mechanism of drug action by EVO in human melanoma cells and suggested its potential value in treating human melanoma by inducing cell death via ROS activation.