Metastatic lung cancer continues to cause a high number of deaths due to high malignancy and poor prognosis, and the efficacy of typical chemotherapy or immunotherapy is less than ideal due to the low pulmonary accumulation and targeting of therapeutics. Here, a submicron-sized biomimetic liposome was formulated for the lung-targeted co-delivery of bacterial superantigen and paclitaxel. Recombinant staphylococcal enterotoxin C2 (rSEC2), a bacterial superantigen, was expressed with the Escherichia coli system and showed potent immunostimulatory activities to mediate tumor cell death. The submicron-sized (∼800 nm) biomimetic liposomes, namely 4T1 cell membrane-hybrid rSEC2 paclitaxel liposomes (TSPLs), exhibited high lung-accumulation efficiency and tumor homologous effect due to the suitable particle size and membrane hybridization of cancer cell membranes with phospholipids. Intravenous TSPLs remarkably inhibited metastatic lung cancer with limited systemic immune responses. TSPLs reversed the immunosuppressive state and increased the proportion of local CD4⁺ and CD8⁺ T cells in the lung; moreover, paclitaxel increased tumor cell apoptosis and reduced tumor burden. In summary, the high lung cancer targeting was achieved by particle size control and cell membrane hybridization, and the highly efficient anticancer effect was achieved by the co-delivery of superantigens and chemotherapeutic drugs.

Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations, leading to enhanced lipid peroxidation. In neurological disorders, both oxidative stress and mitochondrial damage can contribute to ferroptosis, resulting in nerve cell dysfunction and death. The ubiquitin-proteasome system (UPS) refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome. In neurological conditions, the UPS plays a significant role in regulating ferroptosis. In this review, we outline how the UPS regulates iron metabolism, ferroptosis, and their interplay in neurological diseases. In addition, we discuss the future application of small-molecule inhibitors and identify potential drug targets. Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applications in neurological diseases.
Ferroptosis/physiology* ; Humans ; Proteasome Endopeptidase Complex/metabolism* ; Nervous System Diseases/metabolism* ; Animals ; Ubiquitin/metabolism* ; Iron/metabolism*

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4⁺/CD8a⁺ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

Objective:To explore the research hotspots and development trends of mobile health technology applications among family caregivers using bibliometric methods, providing a reference for related studies.Methods:The Web of Science Core Collection was selected as the data source, and research on mobile health technology in family caregivers published from January 1, 2005, to August 31, 2023, was retrieved. Excel, Scimago Graphica, and CiteSpace software were used to create network maps of countries, institutions, authors, and keywords, exploring research hotspots and development trends in this field.Results:A total of 475 relevant articles were included, showing an overall upward trend in annual publication volume. The United States had the highest publication volume (173 articles), with the most influential author and the institution with the highest publication volume being Sin and the University of Washington, respectively. Current research hotspots included chronic diseases, mental health, and social support, while future research trends focus on in-depth studies, artificial intelligence, and enhancing network information security.Conclusions:Research on the application of mobile health technology among family caregivers is on the rise, mainly focusing on assisting caregivers in managing chronic diseases, improving their mental health, and enhancing their social support. Future research frontiers may include optimizing and refining digital health technologies, using artificial intelligence to predict and alleviate caregiver burden, and enhancing industry regulation and data security.

Objective To investigate the feasibility of liver transplantation in the treatment of inoperable hilar cholangiocarcinoma. Methods The clinical data for 3 patients with unresectable hilar cholangiocarcinoma who underwent liver transplantation in the Department of Hepatobiliary Surgery of Fuzhou General Hospital of People's Liberation Army from January 2006 to December 2012 were retrospectively analyzed. The patients were followed up by phone, outpatient service, and hospitalization. The starting point of the follow-up was the operation date. The patients death was the end point. The clinical and pathological features, postoperative survival, tumor recurrence, and prognostic factors were observed. The follow-up deadline was December 2017. Results All 3 patients underwent classical orthotopic liver transplantation using retrograde perfusion through inferior vena cava and no perioperative deaths occurred. All 3 patients were followed up for 10 to 132 months. During the follow-up period, of 1 patient who died of tumor recurrence, the pathological TNM stage was T4a N1 M0, and both had Union for International Cancer Control stage Ⅳa, and the tumor-free survival time was 3 months, and the survival time was12 months. Of 1 patient who died of other causes, the pathological TNM stage was T3N1 M0, and both had Union for International Cancer Control stage Ⅲ, and the tumor-free survival time was 12 months, and the survival time was12 months. One case as of the end of follow-up, the patient has survived for 132 months, the pathological TNM staging was T2a NOM0, and both had Union for International Cancer Control stage Ⅱ. Conclusions Lymph node positive and high pathological TNM stage were poor prognosis factor for hilar cholangiocarcinoma who underwent liver transplantation. Patients with early hilar cholangiocarcinoma who don't have lymph node metastasis are expected to benefit from liver transplantation.

Objective To investigate the biliary complications and recovery of liver function after liver transplantation from citizen's deceased donors (DCD) versus standard criteria donors (SCD).Method The clinical data of 269 patients who underwent orthotopic liver transplantation from January 2009 to December 2016 at the Fuzhou General Hospital were collected.197 livers were from SCD and 72 from DCD.Propensity score matching (PSM) was used to compare the biliary complications and recovery of liver function after liver transplantation in the two groups.Results PSM matched 61 pairs of patients.There were 10 (16.4％) and 8 (13.1％) biliary complications in the DCD and the SCD groups,respectively,with no significant difference between them (P ＞ 0.05).The recovery of liver function was significantly delayed in the DCD group when compared with the SCD group.The levels of ALT,AST,GGT and AKP in the DCD group were significant different on the postoperative first,third,fifth,seventh and fourteenth day (P ＜ 0.05).At 30 days after surgery,there was no significant difference in liver function between the two groups.Conclusions Liver grafts from DCD had a significant impact on the recovery of liver function.When compared with the SCD group,the DCD group recovered significantly slower in liver function.There was no significant increase in the incidence of biliary complications.

Objective To investigate the expression of long-chain non-coding RNA gastric cancer high expression transcription factor 1 (GHET1) in hepatocellular carcinoma (HCC) and the correlation with prognosis,cell proliferation,migration and invasion.Methods 20 HCC patients who underwent surgery from Fuzhou General Hospital of Chinese People's Liberation Army from March to May 2016 were included.The HCC tissue and adjacent normal tissue of 182 patients from June 2012 to December 2013 were retrospectively collected.According to the median value of GHET1 expression,it was divided into GHET1 high expression group and low expression group,91 cases each.Huh7 and HepG2 cells were divided into:blank control group (Con) with serum-free medium,siRNA-GHET1 group transfected with siRNA-GHET1,and negative control group (siRNA-NC) transfected with negative control sequence.The expression of GHET1 was detected by real-time fluorescence quantitative polymerase chain reaction,and the effect of GHET1 on HCC cells was analyzed by CCK-8,Transwell assay and Western blot.Results Compared with adjacent normal tissue,the relative expression of GHET1 mRNA in HCC tissues was significantly increased.Compared with LO2 cells,the mRNA expression of GHET1 in Huh7 and HepG2 cells was higher (P＜0.05).The GHET1 high expression group had tumor＞5 cm,vascular invasion,AFP＞400 μg/L,Edmonson grade Ⅰ,and the tumor-free ratio was lower in the expression group (P＜0.05).Survival analysis showed that HCC patients with high GHET1 expression had a poorer prognosis than patients with low expression.Multivariate Cox regression analysis showed that high expressed GHET1,vascular invasion (HR=2.067,95％ CI:1.350 to 3.162),and without tumor capsule are independent predictors of recurrence in HCC patients.After transfection with Huh7 and HepG2 cells,the proliferation of siRNA-GHET1 group was significantly decreased comparing with Con and siRNA-NC groups.Compared with siRNA-NC group,the migration and invasion ability of siRNA-GHET1 group decreased,and E-cadherin expression increased.The expression of fibronectin and vimentin decreased,and the difference was statistically significant (P＜0.05).Conclusions The expression of GHET1 in HCC tissue is higher comparing with normal tissue,which increases the proliferation,migration and invasion of hepatoma cells.It is an independent predictor of prognosis in HCC patients and a potential target for clinical treatment.

Objective: To investigate the mechanism of apoptosis of CD8⁺T lymphocyte in peripheral blood of patients with hepatocellular carcinoma (HCC). Methods: The proportion and apoptosis of peripheral blood CD8⁺T lymphocytes in 30 healthy controls, 30 patients with cirrhosis and 60 HCC patients were detected by Flow cytometry, and the expression of Fas on the surface of CD8⁺T lymphocytes was reported. The differences between groups were compared using independent sample t-test, and data of variance were tested with Mann-Whitney U non-parametric test, P < 0.05 was considered statistically significant. Results: The proportion of CD8⁺T lymphocytes in peripheral blood of patients with HCC was 26.4% ± 9.2%, higher than that of 24.5% ± 7.1% in cirrhosis (t = 0.783, P = 0.489), and and healthy control 19.7% ± 4.7% (t = 2.920, P = 0.004). The proportion of apoptotic CD8⁺T lymphocytes in peripheral blood of HCC patients was 25.3% ± 6.5%, of the total CD8⁺T lymphocytes, which was significantly higher than that of healthy controls 12.1%±6.5% (t = 7.555, P < 0.001) and cirrhotic 13.6% ± 5.8% (t = 5.213, P < 0.001), the differences were statistically significant. The proportion of Fas⁺CD8⁺T lymphocytes in the HCC group was 62.2% ± 18.5%, higher than that in the healthy control group 42.6%±16.5% (t = 4.127, P < 0.001) and 46.1% ± 14.5% (t = 2.561, P < 0.01)of the cirrhosis group, the differences were statistically significant. Fas expression was positively correlated with the apoptosis of CD8⁺T lymphocytes (r ² = 0.113, P < 0.05). Conclusion The proportion of CD8⁺T lymphocytes in peripheral blood of patients with HCC is higher than that of healthy controls, but the proportion of CD8⁺T lymphocyte apoptosis based on Fas/FasL pathway increased, which may be an important mechanism for tumor cell immune escape.

Objective To compare the safety and efficacy of laparoscopic and open left hepatectomy for hepatocellular carcinoma (HCC).Methods Clinical data of 31 patients with HCC who underwent left hepatectomy in the First People's Hospital of Foshan from June 2011 to December 2017 were retrospectively analyzed.Among 31 patients,24 cases were male and 7 female,aged from 11 to 78 years with a median age of 58 years.Patients were divided into laparoscopic left hepatectomy group (laparoscopic group,n=17) and open left hepatectomy group (open group,n=14).The informed consents of all patients were obtained and the local ethical committee approval was received.In laparoscopic group,two-step Endo-GIA laparoscopic left hepatectomy was performed,and conventional hepatectomy was performed in open group.The postoperative length of hospital stay was compared by t test.The intraoperative blood loss was compared by rank-sum test.The incidence of postoperative complications was compared by Chisquare test.Results All patients underwent operation successfully without perioperative death.The median intraoperative blood loss in laparoscopic group was 100(50-500) ml,significantly less than 325(50-900) ml in open group (Z=-2.180,P＜0.05).The postoperative length of hospital stay in laparoscopic group was (8.4±2.3) d,significantly shorter than (10.9±2.5) d in the open group (t=-2.869,P＜0.05).5 cases developed postoperative pleural effusion in laparoscopic group,and 5 in open group,where no significant difference was observed (x2=0.140,P＞0.05).Conclusions Laparoscopic left hepatectomy is safe for HCC and has similar efficacy as open surgery,the intraoperative blood loss is less comparatively and postoperative recovery time is shorter,which can serve as a standard surgical approach in clinical practice.

Objective To investigate the role of preoperative peripheral blood neutrophil to lymphocyte ratio (NLR),platelet to lymphocyte ratio (PLR),prognostic nutritional index (PNI) in the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after radical operation.Methods This is a retrospective study,involving 426 surgically resected hepatitis B related hepatocellular carcinoma cases in a single center from 2003 to 2012.Results Kaplan-Meier analysis showed patients in NLR ≤ 1.62 group achieve higher rate of recurrence-free and overall survival than that in the NLR ＞ 1.62 group,the difference was statistically significant (P ＜ 0.005);Also PNI ＞ 49.42 group showed higher rate of overall survival significantly than PNI≤49.42 group (P ＜ 0.005).The results of Cox regression multivariate analysis further suggested that both NLR ＞ 1.62 (HR 1.74,P =0.007) and PNI ≤49.42 (HR 0.70,P =0.021) were independent risk factors for overall survival,NLR ＞ 1.62 (HR 1.45,P =0.03) was also an independent risk factor for recurrence-free survival.Conclusion The preoperative NLR and PNI may be independent risk factors for prognosis of patients with HBV-related HCC after radical operation.