The treatment of hepatocellular carcinoma (HCC) faces multiple dilemmas, including limited applicability of local therapy, easy development of resistance to targeted drugs, and low response rate to immune checkpoint inhibitors (ICIs). The core crux lies in the "metabolic reprogramming-immune suppression" vicious cycle and tumor heterogeneity. This review aims to clarify the crosstalk between metabolic reprogramming and immune suppression in HCC, and summarize the design principles of nanoplatforms for synchronous intervention in metabolism and immunity. Nanotechnology, with core advantages of precise targeting, tumor microenvironment responsiveness, and multifunctional synergy, enables targeted regulation of glucose, fatty acid, and amino acid metabolic pathways. It synergizes with ICIs and local therapies to reshape the immunosuppressive microenvironment, and the "metabolic subtype-nanocarrier" matching strategy shows promising clinical potential. Current applications face challenges in carrier performance, personalized strategies, and clinical translation. Future development focusing on carrier optimization, multi-omics-based subtype matching, and standardized evaluation systems will promote nanotechnology to evolve from "broad-spectrum regulation" to "precise adaptation", providing a core tool for overcoming HCC treatment bottlenecks and advancing precision therapy.
The oral‑gut axis is an interorgan regulatory network connecting the two core microbial niches in the human body. It sustains systemic homeostasis through bidirectional microbial translocation, metabolite signaling and immune crosstalk. The present review presented a novel barrier‑metabolism‑immunity three‑dimensional regulatory framework that clarifies the core mechanisms of oral‑gut axis dysregulation: Bidirectional translocation of oral and gut microbiota disrupts microbial homeostasis; key metabolites, including short‑chain fatty acids and trimethylamine N‑oxide, mediate interorgan signaling; immune cell migration and barrier damage collectively constitute the pathological basis, which drives multisystem disorders through secondary axes. The present study classified oral‑gut axis imbalance into three quantifiable subtypes: Barrier‑dominant, metabolism‑dominant and immunity‑dominant, each linked to distinct diseases such as inflammatory bowel disease, type 2 diabetes mellitus and rheumatoid arthritis. Accordingly, a stratified, personalized intervention strategy was proposed. Current challenges include difficulties in causal verification, substantial interindividual variability in intervention efficacy and limited tools for real‑time interorgan tracking. Future research will benefit from microbiota gene editing, multi‑omics integration and in vivo imaging to advance mechanistic understanding and clinical translation. This three‑dimensional model provides a standardized theoretical foundation and practical guidance for the diagnosis and treatment of oral‑gut axis‑related diseases.
Drug resistance in inflammatory bowel disease (IBD) precision therapy remains a critical barrier to clinical outcomes, with traditional studies focusing on single molecules or isolated pathways but failing to systematically dissect the bidirectional, context-dependent dynamic crosstalk among gut microbiota, immunity, and epigenetic modifications. This review dissects resistance mechanisms of key biologics (e.g., antitumor necrosis factor-α agents, vedolizumab) and small-molecule drugs (e.g., janus kinase inhibitors), proposing and validating the “triple-loop hierarchical regulation model”—gut microbiota dysbiosis as the initiator, immune dysregulation as the amplifier, and epigenetic maintenance as the stabilizer, with a bidirectional feedback loop sustaining resistance. It identifies the interaction network as the central regulatory axis, outlining a cascade where altered microbiota composition, signature metabolites (e.g., short-chain fatty acids), epigenetic modification (e.g., acetylation), and Th17/Treg imbalance may collectively contribute to the emergence of drug-resistant phenotypes. Four distinct subtypes (immunogenic, metabolic, epigenetic, barrier-deficient) are defined, with targeted strategies: precise microbiota regulation (e.g., fecal microbiota transplantation), immunity-epigenetics intervention (e.g., histone deacetylase inhibitors), and synergistic schemes that could partially rescue resistant clinical presentations. It also discusses multi-omics biomarkers for early prediction and formulation translation challenges, emphasizing cutting-edge technologies (single-cell multi-omics, organoid-microbiota co-cultures) and interdisciplinary collaboration. This review provides a comprehensive framework for overcoming IBD drug resistance and advancing personalized therapies.
Our previous studies have successfully grafted biotin and galactose onto chitosan (CS) and synthesized biotin modified galactosylated chitosan (Bio-GC). The optimum N/P ratio of Bio-GC and plasmid DNA was 3:1. At this N/P ratio, the transfection efficiency in the hepatoma cells was the highest with a slow release effect. Bio-GC nanomaterials exhibit the protective effect of preventing the gene from nuclease degradation, and can target the transfection into hepatoma cells by combination with galactose and biotin receptors. The transfection rate was inhibited by the competition of galactose and biotin. Bio-GC nanomaterials were imported into cells’ cytoplasm by their receptors, followed by the imported exogenous gene transfected into the cells. Bio-GC nanomaterials can also cause inhibitory activity in the hepatoma cells in the model of orthotopic liver transplantation in mice, by carrying the gene through the blood to the hepatoma tissue. Taken together, bio-GC nanomaterials act as gene vectors with the activity of protecting the gene from DNase degradation, improving the rate of transfection in hepatoma cells, and transporting the gene into the cytoplasm in vitro and in vivo. Therefore, they are efficient hepatoma-targeting gene carriers.
BACKGROUND:In a previous study, autologous bone marrow infusion (ABMI) was performed in patients with decompensated liver cirrhosis (DLC) and acquired immunodeficiency syndrome and achieved good results, but whether splenectomy affected outcome was unclear. AIM:To investigate the efficacy of ABMI combined with splenectomy for treatment of DLC. METHODS:Eighty-three patients with DLC were divided into an intervention group (43 cases) and control group (40 cases) according to whether splenectomy was performed. The control group was treated with ABMI through the right omental vein, and the intervention group was additionally treated with splenectomy. RESULTS:After ABMI, the prothrombin time, serum total bilirubin levels, ascites volume and model for end-stage liver disease score in both groups were significantly lower, while the albumin levels were significantly higher than before ABMI (P < 0.01), but there were no significant differences between the groups (P > 0.05). After ABMI, the white blood cell and platelets counts in both groups were significantly higher than before ABMI (P < 0.01), and the counts in the intervention group were significantly higher than in the control group (P < 0.01). After ABMI the CD4+ and CD8+ T cell counts in both groups were significantly higher than before ABMI (P < 0.01). The CD8+ T cell counts in the intervention group increased continuously and the increase had a shorter duration compared with control group. CONCLUSION:ABMI through the portal vein in patients with DLC can significantly improve liver synthetic and secretory functions, and splenectomy promotes improvement of bone marrow hematopoietic and cellular immune functions.
BackgroundThe global burden of invasive fungal infections (IFIs) has shown an upsurge in recent years due to the higher load of immunocompromised patients suffering from various diseases. The role of early and accurate diagnosis in the aggressive containment of the fungal infection at the initial stages becomes crucial thus, preventing the development of a life-threatening situation. With the changing demands of clinical mycology, the field of fungal diagnostics has evolved and come a long way from traditional methods of microscopy and culturing to more advanced non-culture-based tools. With the advent of more powerful approaches such as novel PCR assays, T2 Candida, microfluidic chip technology, next generation sequencing, new generation biosensors, nanotechnology-based tools, artificial intelligence-based models, the face of fungal diagnostics is constantly changing for the better. All these advances have been reviewed here giving the latest update to our readers in the most orderly flow.Main textA detailed literature survey was conducted by the team followed by data collection, pertinent data extraction, in-depth analysis, and composing the various sub-sections and the final review. The review is unique in its kind as it discusses the advances in molecular methods; advances in serology-based methods; advances in biosensor technology; and advances in machine learning-based models, all under one roof. To the best of our knowledge, there has been no review covering all of these fields (especially biosensor technology and machine learning using artificial intelligence) with relevance to invasive fungal infections.ConclusionThe review will undoubtedly assist in updating the scientific community's understanding of the most recent advancements that are on the horizon and that may be implemented as adjuncts to the traditional diagnostic algorithms.
The 5-year mortality rates associated with decompensated liver cirrhosis (DLC) can reach 50%, which suggests that this condition poses a serious health risk. In previous studies conducted by our group, autologous bone marrow nucleated cells (ABMNCs) were used to treat HIV-positive patients with DLC through the right omental vein; however, trauma and poor compliance were encountered. In the present study, the percutaneous liver approach to inject ABMNCs under the guidance of B-ultrasound was employed for the treatment of DLC. A total of 108 patients with DLC were retrospectively divided into the routine drug treatment group (control group; 30 cases), the right omental vein infusion of ABMNCs group (observation group 1; 38 cases) and the B-ultrasound-guided liver injection of ABMNCs group (observation group 2; 40 cases). After treatment, the liver synthesis (prothrombin time, albumin and ascites) and secretion functions (total bilirubin) in observation groups 1 and 2 were significantly improved compared with those of the control group (P<0.01) and the bone marrow function was also significantly improved compared with that of the control group (P<0.01). While, the bone marrow function (white blood cell, platelet, and hemoglobin) in observation group 1 was significantly improved compared with that of observation group 2 at the end of treatment (P<0.01). After a 1-year follow-up, the case fatality rate was 2.5% (1/40) in observation group 2, which was significantly lower than the 20% fatality rate (6/30) recorded in the control group (P<0.05). The injection of ABMNCs into the liver under the guidance of B-ultrasound was significantly better than conventional drug therapy in treating DLC. This approach has obvious advantages such as no hospitalization, minimal trauma, rapid recovery and good compliance, all of which make it worthy of application in primary hospitals.
The chitosan (CS) material as the skeleton nano-drug delivery system has the advantages of sustained release, biodegradability, and modifiability, and has broad application prospects. In the previous experiments, biotin (Bio) was grafted onto CS to synthesize biotin-modified chitosan (Bio-CS), and it was confirmed that it has liver cancer targeting properties. Single-targeted nanomaterials are susceptible to pathological and physiological factors, resulting in a state of ineffective binding between ligands and receptors, so there is still room for improvement in the targeting of liver cancer. Based on the high expression of folate (FA) receptors on the surface of liver cancers, FA was grafted onto Bio-CS by chemical synthesis to optimize the synthesis of folic acid-modified biotinylated chitosan (FA-CS-Bio), verified by infrared spectroscopy and hydrogen-1 nuclear magnetic resonance spectroscopy. The release of FA-CS-Bio/fluorouracil (5-FU) had three obvious stages: fast release stage, steady release stage, and slow release stage, with an obvious sustained release effect. Compared with Bio-CS, FA-CS-Bio could promote the inhibition of the proliferation and migration of liver cancer by 5-FU, and the concentration of 5-FU in hepatoma cells was significantly increased dose-dependently. Laser confocal experiments confirmed that FA-CS-Bio caused a significant increase in the fluorescence intensity in liver cancer cells. In terms of animal experiments, FA-CS-Bio increased the concentration of 5-FU in liver cancer tissue by 1.6 times on the basis of Bio-CS and the number of monophotons in liver cancer tissue by in vivo dynamic imaging experiments was significantly stronger than that of Bio-CS, indicating that the targeting ability of FA-CS-Bio was further improved. Compared with Bio-CS, FA-CS-Bio can significantly prolong the survival time of 5-FU in the orthotopic liver cancer transplantation model in mice, and has a relieving effect on liver function damage and bone marrow suppression caused by 5-FU. In conclusion, FA-CS-Bio nanomaterials have been optimized for synthesis. In vivo and in vitro experiments confirmed that FA-CS-Bio can significantly improve the targeting of liver cancer compared with Bio-CS. FA-CS-Bio/5-FU nanoparticles can improve the targeted inhibition of the proliferation and migration of liver cancer cells, prolong the survival period of tumor-bearing mice, and alleviate the toxic and side effects.
Abstract In the previous experiments, biotin (Bio) was grafted onto CS to synthesize biotin-modified chitosan (Bio-CS) with liver cancer targeting efficacy, but there is still room for improvement in the targeting of Bio-CS to liver cancer. Based on the high expression of folate (FA) receptors on the surface of liver cancers, FA was grafted onto Bio-CS by chemical synthesis to optimize the synthesis of folic acid-modified biotinylated chitosan (FA-CS-Bio), verified by infrared spectroscopy and 1H-NMR. FA-CS-Bio/Fluorouracil (5-FU) nanoparticles had an obvious sustained release effect. Compared with Bio-CS, FA-CS-Bio could promote the inhibition of the proliferation and migration of liver cancer by 5-FU, and the concentration of 5-FU in hepatoma cells was significantly increased. Laser confocal experiments confirmed that FA-CS-Bio caused a significant increase in the fluorescence intensity in liver cancer cells. In terms of animal experiments, FA-CS-Bio increased the concentration of 5-FU in liver cancer tissue by 1.6 times on the basis of Bio-CS and the number of monophotons in liver cancer tissue by in vivo dynamic imaging experiments was significantly stronger than that of Bio-CS, indicating that the targeting ability of FA-CS-Bio was further improved. Compared with Bio-CS, FA-CS-Bio can significantly prolong the survival time of an orthotopic liver cancer transplantation model in mice and has a relieving effect on liver function damage and bone marrow suppression caused by 5-FU. In conclusion, FA-CS-Bio has significantly improved liver cancer targeting ability, prolonged the survival period of tumor-bearing mice, and alleviated the toxic and side effects caused by 5-FU.
Pancreatic cancer is the worst prognosis of gastrointestinal tumors, and its morbidity and mortality are in a high level. Although many important advances have been made in the study of pancreatic cancer, its prognosis is still poor. And scholars are still looking for new treatments. The theory of cancer stem cell (CSC) provides a new theoretical basis for finding methods of cure pancreatic cancer. As the theory said that sevaral cells that existed in solid tumors or in vitro cell lines have the ability of self-renewal and multi-differentiation, which may play an important role in the development of tumors and the resistance to radiotherapy and chemotherapy. At present, pancreatic cancer stem cells (PCSCs) have been proven to have the malignant characteristics of self-renewal, high tumorigenicity, active differentiation potential and strong drug resistance.
This study aimed to indicate whether autologous bone marrow cell infusion (ABMI) via the right omental vein (ROV) could have a regulatory effect on decompensated liver cirrhosis (DLC) patients with type 2 diabetes mellitus (T2DM). For this purpose, 24 DLC patients with T2DM were divided into observation group (n=14) and control group (n=10). Patients in the observation group were given ABMI through the ROV and right omental artery (ROA), and cases in the control group received ABMI through the ROV. At 1, 3, 6, and 12months after ABMI, it was revealed that the prothrombin time, the total bilirubin levels, and the amount of ascites were significantly lower, while the serum albumin levels in the two groups were markedly higher compared with those before ABMI (p<0.01), and there was no significant difference between the two groups at each time point (p>0.05). The fasting blood glucose and glycosylated hemoglobin levels at 6 and 12months after ABMI in the two groups significantly decreased compared with those before ABMI (p<0.05 or p<0.01), while the decreased levels in the observation group were more obvious than those in the control group at each time point (p<0.01). The amount of insulin in the observation group at 3, 6, and 12months after ABMI was significantly less than that before ABMI in the control group (p<0.01). In summary, ABMI showed a significant therapeutic efficacy for DLC patients with T2DM through ROV and ROA.
目的:观察疏血通联合乌司他丁治疗高脂血症性胰腺炎的疗效,及其对肠道激素和脂肪因子的影响.方法:选择2017年1月至2019年12月在我院诊治的高脂血症性胰腺炎患者70例,按照随机数字法将患者分为观察组和对照组,每组各35例.对照组予以乌司他丁治疗,观察组在对照组的基础上予以疏血通注射液治疗.比较两组患者治疗后的疗效和临床指标,观察两组患者治疗前后甘油三酯(TG),急性生理及慢性健康状况Ⅱ(APACHEⅡ)评分、Balthazar CT评分、胃动素(MTL)、肠抑胃肽(GIP)、血管活性肠肽(VIP)、瘦素、网膜素-1和内脂素水平的变化.结果:观察组的总有效率为97.14%,对照组的总有效率为77.14%,观察组的疗效明显优于对照组(χ2=4.590,P<0.05).观察组患者的腹痛缓解时间、肠鸣音恢复时间、肛门排气恢复时间、恢复进食时间、淀粉酶恢复时间和住院时间短于对照组(P<0.01).两组患者治疗前TG、APACHEⅡ评分、Balthazar CT评分、MTL、GIP、VIP、瘦素、网膜素-1和内脂素水平差异无统计学意义(P>0.05),治疗后两组患者TG、APACHEⅡ评分、Balthazar CT评分、GIP、VIP、网膜素-1和内脂素水平均较治疗前降低(P<0.01),MTL和瘦素水平较治疗前升高(P<0.01),而观察组患者以上指标的降低或者升高较对照组更为明显(P<0.01).结论:疏血通联合乌司他丁治疗高脂血症性胰腺炎疗效显著,有助于胃肠功能恢复、提高疗效,其机理可能与脂肪因子水平变化相关.
目的 观察血清糖类抗原(CA)199,中性粒细胞计数/淋巴细胞计数(NLR)和血小板计数/淋巴细胞计数(PLR)水平在急性胆管炎肾功能损害中的诊断价值.方法 选择2017年1月至2019年12月在我院收住的胆总管结石患者140例,根据是否合并急性胆管炎分为非胆管炎45例(胆总管结石组)和急性胆管炎95例(急性胆管炎组).选择同期在我院健康体检者45例为健康对照组.比较3组血清CA199,NLR和PLR水平变化,及其与急性胆管炎严重程度和肾功能损伤的关系,和预测肾功能损害方面的灵敏度和特异性.结果 急性胆管炎组血清CA199,NLR和PLR水平明显高于胆总管结石组和健康对照组(P<0.01),而胆总管结石组明显高于健康对照组(P<0.01).急性胆管炎患者CA199,NLR和PLR水平随着急性胆管炎严重程度的加重而出现明显升高(P<0.01).急性胆管炎患者肾功能异常组的血清CA199、NLR和PLR水平明显高于肾功能正常组(P<0.01).急性胆管炎患者血清CA199、NLR和PLR在诊断肾功能损伤方面具有较高的灵敏度和特异性,联合CA199、NLR和PLR检测的灵敏度为90.0%,特异性为93.8%,曲线下面积(AUC)为0.933,明显优于CA199(Z=3.322,P<0.01)、NLR(Z=3.042,P<0.01)和PLR(Z=2.301,P<0.05)单个指标检测的AUC,而各个指标在预测肾功能损害方面差异无统计学意义(P>0.05).结论 血清CA199,NLR和PLR水平与急性胆管炎严重程度和肾损害相关,在预测急性胆管炎肾功能损害方面具有较高的灵敏度和特异性.
Microvascular invasion (MVI) is an important predictor of metastatic tumour recurrence and is associated with adverse outcomes and poor prognosis in Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. The association between varying regimens of anti-viral drugs with the incidence of MVI in HBV-related HCC has been demonstrated, however, no meta-analysis of the available data has been conducted. Therefore, the current study sought to evaluate the association of preoperative antiviral therapy with incidence of microvascular invasion in HCC hepatitis virus patients. A systematic search of the literature was performed in MEDLINE/PubMed, Web of Science (WoS), and Scopus, up to January 2020. A random-effects model was used to estimate pooled odds ratios (ORs). Overall, six studies, with 4988 patients, met our inclusion criteria. The pooled OR of MVI in the patients who had preoperative antiviral therapy versus the patients who did not have antiviral therapy was; OR: 0.60, 95% Confidence Interval (CI): 0.49-0.73; I2 = 25%. In this study, a significant reduction in the OR of MVI was evident in patients who had anti-viral therapy.
目的 观察贞芪扶正胶囊联合熊去氧胆酸治疗原发性胆汁性胆管炎(PBC)的疗效,及其对甲状腺功能的影响.方法 在我院诊治的PBC患者70例,随机将患者分为观察组和对照组,每组各35例.对照组予以熊去氧胆酸治疗,观察组在对照组的基础上予以贞芪扶正胶囊治疗.比较两组治疗后的疗效,观察两组治疗前后丙氨酸转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、碱性磷酸酶(ALP)、透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原肽(PCⅢ)、基质金属蛋白酶组织抑制因子-1(TIMP-1)、总三碘甲状腺原氨酸(TT3)、游离三碘甲状腺原氨酸(FT3)、总甲状腺素(TT4)和游离甲状腺素(FT4)水平的变化.结果 观察组的总有效率为97.14%,对照组的总有效率为77.14%(P<0.05).两组治疗后血清ALT、AST、TBIL、ALP、HA、TIMP-1、LN和PCⅢ水平均较治疗前明显降低(P<0.01),两组血清TT3、FT3、TT4和FT4水平均较治疗前明显升高(P<0.01),而观察组的降低或者升高水平与对照组比较更加明显(P<0.01).结论 贞芪扶正胶囊联合熊去氧胆酸治疗原发性胆汁性胆管炎的疗效显著,能够改善机体的纤维化,缓解甲状腺功能低下.
Liver stem cell therapy is a promising tool to improve decompensated liver cirrhosis (DLC). Especially in patients infected with human immunodeficiency virus (HIV), the condition of the liver may be aggravated by antiretroviral therapy. A total of 21 patients diagnosed with DLC and HIV infection were divided into two groups as follows: those who received (combination therapy group, 14 patients) and those who did not receive (routine therapy group, 7 patients) bone marrow cell transplantation through the portal vein. Two patients died of surgery-related complications in the combination therapy group. The results showed that the survival rate was 85.7% in the combination therapy group after 2 years of follow-up, which was significantly higher than the 14.3% in the conventional therapy group (P<0.01). After treatment, the liver function score decreased significantly in the combination therapy group at 1 (t = 4.276, P = 0.000), 3 (t = 9.153, P = 0.000), and 12 (t = 13.536, P = 0.000) months, the levels of albumin were significantly increased, and the total bilirubin level and prothrombin time were significantly reduced or shortened as compared with the routine therapy group (P<0.05 or <0.01). The white blood cell count, hemoglobin, platelet count, and CD4+ and CD8+ levels were significantly higher in the combination therapy group at different time points as compared with the routine therapy group (P<0.05 or <0.01). In summary, the combination therapy is effective in HIV-infected patients with DLC and useful for the recovery of liver function and cellular immune function but may increase the risk of severe complications after surgery.
Chemotherapy may aggravate the immune damage of AIDS with malignant tumors, but chemotherapy is a necessary treatment. One patient with AIDS complicated with Kaposi’s sarcoma and developed severe immune damage and perianal infection after a course of chemotherapy. Sigmoid colostomy and intravenous catheterization were performed. Before the second chemotherapy, autologous bone marrow was collected for preservation, and day 5 after the end of chemotherapy, the autologous bone marrow was transferred back to the port by buried infusion. The bone marrow was preserved before each chemotherapy and the preserved bone marrow was restored after chemotherapy. After 6 times chemotherapy, CD4+ T cells increased and infection around anus healed. It is suggested that the preservation of autologous bone marrow can promote the immune reconstruction after chemotherapy.
BACKGROUND/AIMS:Our previous study found that a nanoparticle drug delivery system that operates as a drug carrier and controlled release system not only improves the efficacy of the drugs but also reduces their side effects. However, this system could not efficiently target hepatoma cells. The aim of this study was to synthesize biotin-modified galactosylated chitosan nanoparticles (Bio-GC) and evaluate their characteristics in vitro and in vivo.METHODS:Bio-GC nanomaterials were synthesized, and confirmed by fourier transform infrared spectroscopy (FT-IR) and hydrogen-1 nuclear magnetic resonance (1H-NMR). The liver position and cancer target property of Bio-GC nanoparticles in vitro and in vivo was tested by confocal laser and small animal imaging system. The characteristics of Bio-GC/5-fluorouracil (5-FU) nanoparticles in vitro and in vivo were explored by cell proliferation, migration and cytotoxicity test, or by animal experiment.RESULTS:Bio-GC nanoparticles were synthesized with biodegradable chitosan as the nanomaterial skeleton with biotin and galactose grafts. Bio-GC was confirmed by FT-IR and 1H-NMR. Bio-GC/5-FU nanoparticles were synthesized according to the optimal mass ratio for Bio-GC/5-FU (1: 4) and had a mean particle size of 81.1 nm, zeta potential of +39.2 mV, and drug loading capacity of 8.98%. Bio-GC/5-FU nanoparticles had sustained release properties (rapid, steady, and slow release phases). Bio-GC nanoparticles targeted liver and liver cancer cell in vitro and in vivo, and this was confirmed by confocal laser scanning and small animal imaging system. Compared with GC/5-FU nanoparticles, Bio-GC/5-FU nanoparticles showed more specific cytotoxic activity in a dose- and time-dependent manner and a more obvious inhibitory effect on the migration of liver cancer cells. In addition, Bio-GC/5-FU nanoparticles significantly prolonged the survival time of mice in orthotopic liver cancer transplantation model compared with other 5-FU nanoparticles or 5-FU alone. Bio-GC (0.64%) nanomaterial had no obvious cytotoxic effects on cells; thus, the concentration of Bio-GC/5-FU nanoparticles used was only 0.04% and showed no toxic effects on the cells.CONCLUSION:Bio-GC is a liver- and cancer-targeting nanomaterial. Bio-GC/5-FU nanoparticles as drug carriers have stronger inhibitory effects on the proliferation and migration of liver cancer cells compared with 5-FU in vitro and in vivo.
Objective To compare the curative effects of primary closure and T-tube drainage after laparoscop-ic cholecystectomy(LC)combined with laparoscopic common bile duct exploration(LCBDE)treated on cholecystolithi-asis and choledocholithiasis.Methods A total of 177 patients with cholecystolithiasis and choledocholithiasis,admitted to Department of Biliary and Pancreatic Surgery of Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between July 2014 and March 2016, were selected and divided into the primary closure group (n=88) and T-tube drainage group(n=89)according to random number table method.The efficiency,safety,economy of the opera-tion,postoperative gastrointestinal quality of life questionnaire,as well as the surgical tolerance between the two groups were compared. Results There was no significant difference in the surgery success rate between the primary closure group and T-tube drainage group(both 95.5%,P>0.05).The incidence rate of complications was 12.4% in the primary closure group versus 11.4% in the T-tube drainage group(P>0.05).However,the primary closure group were significant-ly higher than the T-tube drainage group in terms of operative time,hospitalization expenses,postoperative hospitalization time, postoperative Gastrointestinal Quality of Life Index (GIQLI) (P<0.05). Conclusion Primary closure after LC+LCBDE has similar success rate and complication incidence rate with T-tube drainage after LC+LCBDE in the treatment of cholecystolithiasis and choledocholithiasis,but primary closure after LC+LCBDE has simplicity of operation,less mini-mal invasive,rapid recovery,less cost and higher postoperative survival quality,which may be used as the first choice.
The present study investigated the synthesis of biotinylated chitosan (Bio-CS) from chitosan using a nanomaterial skeleton with biotin and the successful targeting of the formulation in liver cancer cells. Bio-CS was validated by fourier transformed infrared spectroscopy and hydrogen-1 nuclear magnetic resonance spectroscopy. Bio-CS and plasmid DNA were used to construct Bio-CS/plasmid DNA nanoparticles according to the optimal molar ratio of 1: 1 and the optimal pH-value of 5.5. Under these conditions, the parameters mean particle size, potential, encapsulation rate and drug loading, were 82.9 nm, +21.8 mV, 85.7% and 35.4%, respectively. Bio-CS exhibited an apparent liver cancer targeting effect in vitro and in vivo, as demonstrated by confocal laser scanning, green fluorescent protein transfection, and in vivo imaging assays. In addition, the Bio-CS/plasmid DNA nanoparticles significantly increased the survival period of the orthotropic liver cancer mouse model compared with the plasmid DNA, with no apparent side effects on the cells. Bio-CS nanomaterials stimulated an immune response in hepatoma cells via increased expression of GM-CSF, IL-21 and Rae-1 markers. The data suggest that Bio-CS increased the inhibition of liver cancer cell proliferation in vitro and the activation of the cellular immunity in vivo.