The role of SLC26A3 in the sensitivity to oxaliplatin, a widely used chemotherapy drug for colorectal cancer (CRC), remains unclear. This study aimed to explore the association between SLC26A3 expression and oxaliplatin sensitivity. Total 240 differentially expressed mRNAs were identified, with 124 downregulated and 116 upregulated in oxaliplatin-resistant CRC. WGCNA identified a module significantly associated with resistance. GO and KEGG analyses revealed enrichment in fatty acid metabolic processes and organic anion transmembrane transporter activity. PCA and feature gene selection identified a 15-gene signature, with SLC26A3 highlighted by machine learning models as a key discriminator of chemosensitivity. Immunohistochemical staining and survival analysis indicated that higher SLC26A3 expression correlated with better survival outcomes. Additionally, a significant negative correlation between SLC26A3 and AKT1 was observed, suggesting that while SLC26A3 may enhance oxaliplatin sensitivity, its effect may be overshadowed by other factors in resistant cells. SLC26A3 may play a crucial role in oxaliplatin sensitivity in CRC. The identified gene signature could potentially serve as a biomarker for predicting chemosensitivity to oxaliplatin.

Purpose5-Fluorouracil (5-FU) resistance is considered to be a possible reason for the failure of conventional drug treatment of colorectal cancer (CRC). Recently, salinomycin (SAL), as a selective inhibitor of cancer stem cells (CSCs), has been used to sensitize and attenuate a variety of solid tumor chemotherapy drugs. In our study, our goal was to combine SAL with 5-FU to explore not only whether there is an increase in sensitivity of CRC to 5-FU but also the molecular mechanism involved in enhancing 5-FU sensitivity and promoting tumor cell chemotherapeutic death.MethodsComboSyn software was used to study whether dual drug combinations synergistically promote each other and their dosage. CCK8, EdU, and Annexin V/PI assays were used to study the cell proliferation and apoptosis of SW480 and HCT116 cells in response to SAL single-drug and dual-drug co-treatment. Cell cycle staining was used to assess cycle arrest. Wound healing and migration and invasion experiments were used to identify changes in migration and invasion capabilities under the influence of different drugs. Transcriptome sequencing is used to explore the molecular mechanisms of drugs. Reactive oxygen species (ROS) fluorescence staining and malondialdehyde (MDA) level measurement were used to confirm the changes in ferroptosis levels of SW480 and HCT116 cells after drug treatment. Nude xenograft mice were used to detect antitumor in vivo. Changes in the protein level expression of ferroptosis GPX4 and SLC7A11 were also determined in the treated cells.ResultsSAL alone and in combination with 5-FU were found to significantly increase cell mortality and apoptosis. At the same time, our results show that the combination of SAL and 5-FU not only inhibits the proliferation, migration, and invasion of CRC cell lines in vivo and in vitro, but also promotes ferroptosis of CRC cell lines by downregulating the expression of GPX4 and SLC7A11. It may provide more and novel solutions and treatment perspectives for 5-FU or other drug-resistant chemotherapy strategies for patients with CRC.ConclusionsSAL inhibits CRC, whose effect is achieved by reducing GPX4 and SLC7A11 protein levels to mediate ferroptosis activation in collaboration with 5-FU.

The immune system and the tumor have been at each other's throats for so long that the neoplasm has learned to avoid detection and avoid being attacked, which is called immune evasion. Malignant tumors, such as gastric cancer (GC), share the ability to evade the body's immune system as a defining feature. Immune evasion includes alterations to tumor-associated antigens (TAAs), antigen presentation mechanisms (APMs), and the tumor microenvironment (TME). While TAA and APM are simpler in nature, they both involve mutations or epigenetic regulation of genes. The TME is comprised of numerous cell types, cytokines, chemokines and extracellular matrix, any one of which might be altered to have an effect on the surrounding ecosystem. The NF-kB, MAPK, PI3K/AKT, JAK/STAT, Wnt/β-catenin, Notch, Hippo and TGF-β/Smad signaling pathways are all associated with gastric cancer tumor immune evasion. In this review, we will delineate the functions of these pathways in immune evasion.

Intratumoral abundance of alternatively activated macrophages (M2) in hepatocellular carcinoma (HCC) is associated with advanced stages, poor prognosis and failure of checkpoint blockade immunotherapy. In this work, we discover that synthetic high-density lipoproteins (sHDLs) preferentially deliver cargoes into M2 and Hepa1–6 HCC cells, based on which finding we create a functional sHDL containing esterase-responsive prodrugs of vadimezan and gemcitabine (VG-sHDLs). The VG-sHDLs induce the HCC cells to release damage-associated molecular patterns (high mobility group box 1 protein and ATP) and cytokines including macrophage colony stimulating factor and type I interferons, improving monocyte differentiation into classically activated macrophages (M1) and dendritic cells. Meanwhile, the VG-sHDLs kill M2 without significant toxicity to M1. After intravenous injection, the VG-sHDLs increase intratumoral M1 as well as proinflammatory molecules such as C-X-C motif ligand 9 and 10 and interleukin 12, but reduce M2 and anti-inflammatory cytokine interleukin 10. These changes enhance the recruitment and activity of cytotoxic T lymphocytes, which eradicate HCC tumors and also establish tumor-specific immune memory that prevents recurrence. This work sheds light on the interactions between sHDL and intratumoral cells, and provides rationale for chemoimmunotherapy of HCC using conventional chemotherapeutics and emerging immune modulators.

Immunotherapy has revolutionized the field of cancer therapy. Nanomaterials can further improve the efficacy and safety of immunotherapy because of their tunability and multifunctionality. A supramolecular peptide assembly (SPA), as a close mimic of natural viruses, is a unique type of nanomaterial with high epitope valency, multifunctionality and biocompatibility. Given its great potential in cancer immunotherapy, especially in cancer vaccines, in the current review, we summarize the unique features of the SPA that are beneficial for cancer immunotherapy, and highlight the important progress in using SPAs as nanoscale carriers, antigens, adjuvants or multifunctional platforms. The current challenges faced by these SPAs are also briefly discussed.

Adenocarcinoma of esophagogastric junction (AEG) has attracted more attention in recent years. Surgical method of Siewert type Ⅱ AEG is especially controversial, mainly focusing on the scope of lymph node dissection, safety of surgical margin, and digestive tract reconstruction. The abdominal transhiatal approach and right thoracoabdominal Ivor-Lewis approach are the main surgical approaches of totally laparoscopic or thoracoscopic surgery for Siewert type Ⅱ AEG, which not only need close teamwork, but also require rich experience in laparoscopic surgery. The authors has started to choose these two totally minimally invasive surgical approaches, the feasibility and safety of which are proved. The key surgical details are presented in this article for reference.

The Warburg effect in tumor cells involves the uptake of high levels of glucose, enhanced glycolysis, and the metabolism of pyruvate to lactic acid rather than oxidative phosphorylation to generate energy under aerobic conditions. This effect is closely related to the occurrence, invasion, metastasis, drug resistance, and poor prognosis of gastric cancer (GC). Current research has further demonstrated that the Warburg effect in GC cells is not only mediated by the glycolysis pathway, but also includes roles for mitochondria, noncoding RNAs, and other proteins that do not directly regulate metabolism. As a result, changes in the glycolysis pathway not only lead to abnormal glucose metabolism, but they also affect mitochondrial functions, cellular processes such as apoptosis and cell cycle regulation, and the metabolism of lipids and amino acids. In this review, we discuss metabolic reprogramming in GC based on glycolysis, a possible link between glucose metabolism, lipid metabolism, and amino acid metabolism, and we clarify the role of mitochondria. We also examine recent studies of metabolic inhibitors in GC.

The long progression-free survival (PFS) of patients with inoperable hepatocellular carcinoma (HCC) tumors is an unmet clinical need. Imaging-guided in situ ablation and vaccination with nanoplatforms could be a promising way to achieve durable disease control and long PFS. In the present work, we show that a biomimetic nanoplatform, namely, synthetic high-density lipoprotein (sHDL), can transport photothermal agent DiR and other drugs preferentially into the cytosol of HCC cells, enabling imaging-guided combination therapy for HCC in vivo. With a single injection, the sHDLs reduced the tumor burden, triggered immunogenic cell death (ICD), promoted dendritic cell (DC) maturation, and induced CD8(+) T cell responses, which together sensitized the tumors to PD-1 blockade. Tumor remission and immune protection were achieved using sHDL loaded with DiR and a stimulator of interferon genes agonist vadimezan, in conjunction with a PD-1 blockade. The replacement of vadimezan with the chemotherapeutic mertansine potentiated ICD of HCC cells, but the drug interfered with DC maturation and subsequent CD8(+) T cell priming, resulting in unsatisfactory disease control. Our work provides a generalizable nanoplatform for the combined photothermal ablation and immunotherapy of HCC and highlights the importance of cancer-cell-specific ICD induction and simultaneous DC activation during in situ vaccination.

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C16-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days in vitro, with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.

Triple-negative breast cancer (TNBC) tumors are heterogeneous, with mesenchymal-like cells at their core and fast proliferating cells on the periphery. It is desirable and beneficial to treat TNBC cells of different phenotypes with the most appropriate drugs. Here, we report a 78 nm, chlorin e6-, docetaxel-, and anti-Twist siRNA-containing polymeric nanoparticle (CDTN) with spatiotemporally specific activity when irradiated by light. Under conditions mimicking superficial tumor tissue with sufficient light input, TNBC cells are mainly killed by the photodynamic therapy (PDT) function of CDTNs. In contrast, under conditions mimicking deep tumor tissue with weak light input, PDT potentiates chemotherapy (CT) and gene therapy (GT) by facilitating the endolysosomal escape of CDTNs. Compared with free drugs, CDTNs improve the intratumoral exposure of docetaxel and anti-Twist siRNA by 2.5- and 2-fold, respectively. When combined with laser irradiation applied at the time of maximal intratumoral accumulation, the CDTNs significantly inhibit the growth of primary tumors and their lung metastasis (both >80%) by killing the peripheral cells, mainly through PDT and prohibiting the growth and metastasis of deep cells through PDT as enhanced CT and GT. On the contrary, dual-modality nanomedicine lacking CT, GT, or PDT showed fast primary tumor growth, poor metastasis control, or both, respectively. This study reveals the spatiotemporally specific mechanism of CDTNs in treating metastatic TNBC and highlights the importance of combined therapy in treating TNBC.

Objective To value the clinical effect of laparoscopic and open hernia sac high ligation for pediatric patients in a randomized controlled trial. Methods The pediatric patients who suffered from inguinal hernias hospitalized in the second hospital of Jilin University during January 2014 to December 2015 were divided randomly into laparoscopic group (group A, n=47) and open group (group B, n=47). And then indexes of operating time, treatment cost, hospitalization time after operation, leaving bed time after operation, scrotal edema and recurrence rate were compared. Results Compared with group B, group A had shorter operation time ( bilateral) , hospitalization time after operation and leaving bed time after operation. There were significant differences between the two groups( t=-3. 07,-4. 43,-4. 15, P=0. 007, <0. 001, 0. 001). Conclusion Laparoscopic hernia sac high ligation can make a quick recovery.

Objective To study the the feasibility of intestinal derotation maneuver in the resection of gastrointestinal neoplam localized in the vicinity of the ligament of Treitz.Method Intestinal derotation maneuver was applied in all the 9 case of gastrointestinal neoplasms near the ligament of Treitz,from January 2014 to January 2016,at the Second Hospital of Jilin University.The clinical date were retrospectively analyzed.Results Intestinal derotation maneuver were applied without failure in all the nine patients,the mean operation time were (195 ± 50) min,and the mean intestinal derotation maneuver time were (19 ±5) min;No derotation procedure-related injury occured,and the mean estimated blood loss were (132 ±94) ml.Early postoperative ileus developed in one case and gastroparesis in two cases.All were recovered by conservative treatment.The follow-up period were 3-24 month,tumor recurrence occurred in two cases and one case died.One case lossed to follow-up after postoperative 3 month.Conclusion The present data suggest that clinical use of intestinal derotation maneuver was feasible for surgical management of gastrointestinal neoplasms near the ligament of Treitz.

目的讨论肠内营养与肠外（静脉）营养对胃肠道恶性肿瘤患者术后营养状况、术后并发症、免疫功能、及住院时间的影响。方法针对我院2009-2011年间92例确诊胃肠道恶性肿瘤并行手术治疗患者随机分为:观察组50例（肠内营养组）和对照组42例（肠外营养组）,在术前1d及术后3d和7d抽取静脉血,检测淋巴细胞总数、T淋巴细胞亚群（CD3、CD4、CD8、CD4/CD8）和体重、血清白蛋白、前白蛋白等营养状况,并比较两组的并发症发生率、住院时间、发热时间等指标。结果观察组与对照组患者体重均有下降,但观察组患者的白蛋白和前白蛋白升高水平均高于对照组;两组患者术后的淋巴细胞总数、CD3+、CD4+、CD8+细胞、CD4+/CD8+比值降低,但是观察组的回升高于对照组;且观察组的并发症发生率明显低于对照组、发热时间及住院时间明显短于对照组。结论胃肠道恶性肿瘤术后早期肠内营养较肠外营养更具优越性,可降低术后并发症发生率,缩短住院时间,能提高患者的营养水平及免疫功能。

目的 比较胃癌术后肠外营养(PN)联合早期肠内营养(EN)与单纯肠内营养支持的效果,探讨其对于胃癌患者术后早期营养状态、免疫功能及并发症等方面的影响.方法 我院2011～2013年间50例确诊为胃癌并行根治手术治疗的患者随机分为观察组和对照组,观察组27例患者术后接受肠外营养与早期肠内营养(EN+PN),对照组23例仅行单纯肠内营养(EN),检测患者术前、术后淋巴细胞总数、T淋巴细胞亚群(CD3、CD4、CD8、CD4/CD8)和体重、血清白蛋白、前白蛋白等营养指标,并比较两组患者吻合口瘘、腹胀、腹泻等并发症发生率以及发热时间、住院时间.结果 两组患者年龄、性别、术前BMI、胃切除方式、临床分期比较差异无统计学意义.与术前比较,观察组与对照组患者术后8天体重均有下降,白蛋白和前白蛋白水平均有升高;但观察组体重下降幅度显著低于对照组,营养指标升高幅度显著大于对照组.两组患者术后淋巴细胞总数、CD3+、CD4+、CD8+细胞、CD4+/CD8+比值均降低,术后3天开始回升,观察组术后7天升高幅度显著高于对照组.观察组术后吻合口瘘、腹胀、腹泻等并发症发生率以及发热时间、住院时间显著低于对照组.结论 胃癌术后肠外营养与早期肠内营养联合应用较单纯肠内营养更具优越性,可降低术后并发症发生率,缩短住院时间,改善患者的营养水平及免疫功能.

<正>胰十二指肠切除术(PD)曾是壶腹周围癌的标准术式。保留幽门的胰十二指肠切除术(PPPD)目前已成为治疗慢性胰腺炎和壶腹周围癌首选的手术方式〔1〕。PPPD较传统的PD减少了壶腹区肿瘤近端胃的切除范围,保留了胃的储存和消化功能。本文总结10例行PPPD的临床资料,进行疗效分析。

目地探讨原发性甲状腺功能亢进症(原发性甲亢)合并甲状腺癌(甲癌)的诊治方法。方法回顾性分析我院2009年7月～2013年2月经手术及病理证实的9例原发性甲亢合并甲癌临床资料,分析其诊断及治疗。结果在本组9例原发甲亢合并甲状腺癌的病例中,术前细针穿刺细胞学检查确诊2例,术前误诊、漏诊率高达77.8%(7/9)。术中快速病理明确诊断88.9%(8/9)。1例术后病理检查明确诊断。9例患者均行手术治疗,行患侧甲状腺全切除术+对侧甲状腺次切除术6例,甲状腺全切除术3例(其中1例为二次手术)。术后均服用左旋甲状腺素片进行内分泌治疗。所有患者均获随访,无一例复发、转移或死亡。结论原发甲亢合并甲状腺癌近年患者有所增多;术前诊断比较困难,术前应综合运用B超、细针穿刺细胞学等检查,本病的确诊有赖于病理学诊断,术前、术中明确诊断,避免患者行第二次手术。采取合理的手术方式,术后再根据甲功结果服用左旋甲状腺素片,患者术后疗效较好。

目前,胃癌在癌症死因中位列第二,位据消化道肿瘤的首位[1],至今,主要采取以手术、化疗、靶向治疗、放疗、免疫治疗等的综合治疗。在我国进展期胃癌（AGC）占胃癌比例的92%-95%[2]。外科手术是治疗AGC的最佳手段,效果并不理想,具报道其术后患者总的5年生存率为30%-50%[3]。追溯120