Emerging advances in delivery systems for mRNA cancer vaccines.

The success of lipid nanoparticles (LNPs) in treating COVID-19 promotes further research of mRNA vaccines for cancer vaccination. Aiming at overcoming the constraints of currently available mRNA carriers, various alternative nano-vectors have been developed for delivering tumor antigen encoding mRNA and showed versatility to induce potent anti-tumor immunity. The rationally designed nano-vaccines increase the immune activation capacity of the mRNA vaccines by promoting crucial aspects including mRNA stability, cellular uptake, endosomal escape and targeting of immune cells or organs. Herein, we summarized the research progress of various mRNA based nano-vaccines that have been reported for cancer vaccination, including LNPs, lipid enveloped hybrid nanoparticles, polymeric nanoparticles etc. Several strategies that have been reported for further enhancing the immune stimulation efficacy of mRNA nano-vaccines, including developing nano-vaccines for co-delivering adjuvants, combination of immune checkpoint inhibitors, and optimizing the injection routes for boosting immune responses, have been reviewed. The progress of mRNA nano-vaccines in clinical trials and the prospect of the mRNA vaccines for cancer vaccination are also discussed.

Retrospective analysis of preoperative application of triple-modal pre-rehabilitation on postoperative recovery of colorectal cancer patients.

PURPOSE: To retrospectively analyze the difference between triple-modal pre-rehabilitation and common treatment in patients with colorectal cancer (CRC). METHODS: A total of 145 patients with CRC diagnosed by pathology and admitted to our hospital for surgery between June 2020 and June 2022 were included in the study. All patients were divided into two groups: the triple-modal pre-rehabilitation group (pre-rehabilitation group) and the common treatment group. The triple-modal pre-rehabilitation strategy included exercise (3-5 times per week, with each session lasting more than 50 min), nutritional support, and psychological support. The study was designed to assess the potential of the pre-rehabilitation intervention to accelerate postoperative recovery by assessing the 6-min walk test, nutritional indicators, and HADS score before and after surgery. RESULTS: The pre-rehabilitation intervention did not reduce the duration of initial postoperative recovery or the incidence of postoperative complications, but it did increase the patients' exercise capacity (as determined by the 6-min walk test), with the pre-rehabilitation group performing significantly better than the common group (433.0 (105.0) vs. 389.0 (103.5), P < 0.001). The study also found that triple-modal pre-rehabilitation was beneficial for the early recovery of nutritional status in surgical patients and improved anxiety and depression in patients after surgery, especially in those who had not received neoadjuvant therapy. CONCLUSION: The triple-modal pre-rehabilitation strategy is of significant importance for reducing stress and improving the functional reserve of patients with colorectal cancer (CRC) during the perioperative period. The results of our study provide further support for the integration of the triple-modal pre-rehabilitation strategy into the treatment and care of CRC patients.

Study on the cut-off point and the influencing factors of distress in newly diagnosed breast cancer patients.

Objective: Our aim is to investigate the cut-off point of distress and the influencing factors associated with distress in patients with newly diagnosed breast cancer. Methods: A cross-sectional survey of distress was conducted in 167 patients with newly diagnosed breast cancer admitted to the Department of General Surgery of a tertiary care hospital from July 2020 to March 2022. Patients completed the Hospital Anxiety and Depression Scale (HADS) and the Distress Thermometer (DT) questionnaire within 3 days of admission. The HADS ≥15 was used as the gold standard, and the cut-off point of the DT measure was analyzed using the Receiver Operating Characteristic (ROC) curve. The cut-off point obtained by ROC curve analysis was used to analyze the influencing factors of distress in breast cancer patients by univariate and multivariate regression analysis. Results: A total of 167 patients completed the survey, with an average HADS score of 8.43 ± 5.84 and a total HADS score of ≥15 in 37 (22.16%) patients, the mean DT score was 2.96 ± 1.85. ROC curve analysis showed an area under the curve of 0.885, with a maximum Jorden index (0.723) at a DT score of 4, the sensitivity was 100.0% and specificity was 72.3%. There were 73 (43.71%) patients with DT score ≥ 4. Regression analysis showed that insurance/financial problems, dealing with partner problems, tension, bathing/dressing problems, pain, and sleep problems were independent risk factors for l distress in newly diagnosed breast cancer patients. Conclusion: A DT score 4 is the cut-off point for distress in patients with newly diagnosed breast cancer. In clinical practice, target intervention should be carried out according to the risk factors of distress of patients.

Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Co-delivery of oxaliplatin prodrug liposomes with Bacillus Calmette-Guérin for chemo-immunotherapy of orthotopic bladder cancer.

To reduce recurrence rate after transurethral resection of bladder tumor, long-term intravesical instillations of Bacillus Calmette-Guérin (BCG) and/or chemotherapeutic drugs is the standard treatment for non-muscle invasive bladder carcinoma. However, the main challenges of intravesical therapy, such as short retention time and poor permeability of drugs in the bladder, often require frequent and high-dose administrations, leading to significant adverse effects and financial burden for patients. Aiming at addressing these challenges, we developed a novel approach, in which the cell-penetrating peptide modified oxaliplatin prodrug liposomes and a low-dose BCG were co-delivered via a viscous chitosan solution (LRO-BCG/CS). LRO-BCG/CS addressed these challenges by significantly improving the retention capability and permeability of chemotherapy agents across the bladder wall. Then, oxaliplatin triggered the immunogenic cell death, and the combination of BCG simultaneously further activated the systemic anti-tumor immune response in the MB49 orthotopic bladder tumor model. As a result, LRO-BCG/CS demonstrated superior anti-tumor efficacy and prolonged the survival time of tumor-bearing mice significantly, even at relatively low doses of oxaliplatin and BCG. Importantly, this combinational chemo-immunotherapy showed negligible side effects, offering a promising and well-tolerated therapeutic strategy for bladder cancer patients.

Cellular specificity of lactate metabolism and a novel lactate-related gene pair index for frontline treatment in clear cell renal cell carcinoma.

Background: Although lactate metabolism-related genes (LMRGs) have attracted attention for their effects on cancer immunity, little is known about their function in clear cell renal cell carcinoma (ccRCC). The aim of this study was to examine the cellular specificity of lactate metabolism and how it affected the first-line treatment outcomes in ccRCC. Methods: GSE159115 was used to examine the features of lactate metabolism at the single-cell level. Utilizing the transcriptome, methylation profile, and genomic data from TCGA-KIRC, a multi-omics study of LMRG expression characteristics was performed. A prognostic index based on a gene-pair algorithm was created to assess how LMRGs affected patients' clinical outcomes. To simulate the relationship between the prognostic index and the frontline treatment, pRRophetic and Subclass Mapping were used. E-MTAB-1980, E-MTAB-3267, Checkmate, and Javelin-101 were used for external validation. Results: The variable expression of some LMRGs in ccRCC can be linked to variations in DNA copy number or promoter methylation levels. Lactate metabolism was active in tumor cells and vSMCs, and LDHA, MCT1, and MCT4 were substantially expressed in tumor cells, according to single-cell analysis. The high-risk patients would benefit from immune checkpoint blockade monotherapy (ICB) and ICB plus tyrosine kinase inhibitors (TKI) therapy, whereas the low-risk individuals responded to mTOR-targeted therapy. Conclusions: At the single-cell level, our investigation demonstrated the cellular specificity of lactate metabolism in ccRCC. We proposed that the lactate-related gene pair index might be utilized to identify frontline therapy responders in ccRCC patients as well as predict prognosis.

An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer.

The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.

Resection of sigmoid cancer with bladder invasion using laparoscopic combined with a cystoscopic holmium laser: an innovative surgical procedure.

The aim of this study was to introduce a new surgical procedure for the resection of sigmoid colon tumours invading the bladder by combining laparoscopy and cystoscopy, and the feasibility and safety of the method were verified. The data of 6 patients with sigmoid colon cancer invading the bladder in a tertiary hospital in Chongqing from January 2020 to October 2022 were collected, sigmoid colon tumour resection was performed by this procedure, and the data related to the surgery were recorded. All six patients successfully underwent sigmoid colon tumour resection, and all sigmoid colon and bladder resections had negative margins. The mean total operative time was 211.66 ± 27.33 min, and the mean resection time of the bladder tumour was 22.16 ± 4.63 min. The median blood loss was 100 ml, and the mean number of retrieved lymph nodes was nineteen. There were no serious intraoperative complications in any of the cases. After operation, the first flatus and defecation were 4 and 4.5 days, respectively. The mean time of drainage tube retention and the time of bladder flushing were 3 and 1.5 days, respectively. The mean time of urinary tube retention was 7.5 days. There were no intestinal obstructions, dysuria, or other complications. For patients with sigmoid colon tumours invading the bladder, this method can effectively resect sigmoid colon tumours and minimize the loss of bladder tissue at the same time, which helps to prolong the survival of these patients. The surgical method is safe, reliable, and feasible.

Recent progress in application of nanovaccines for enhancing mucosal immune responses.

Mucosal vaccines that stimulate both mucosal and systemic immune responses are desirable, as they could prevent the invading pathogens at their initial infection sites in a convenient and user-friendly way. Nanovaccines are receiving increasing attention for mucosal vaccination due to their merits in overcoming mucosal immune barriers and in enhancing immunogenicity of the encapsulated antigens. Herein, we summarized several nanovaccine strategies that have been reported for enhancing mucosal immune responses, including designing nanovaccines that have superior mucoadhesion and mucus penetration capacity, designing nanovaccines with better targeting efficiency to M cells or antigen-presenting cells, and co-delivering adjuvants by using nanovaccines. The reported applications of mucosal nanovaccines were also briefly discussed, including prevention of infectious diseases, and treatment of tumors and autoimmune diseases. Future research progresses in mucosal nanovaccines may promote the clinical translation and application of mucosal vaccines.

Crosstalk between autophagy and bladder transitional cell carcinoma by autophagy-related lncRNAs.

The aim of this study was to investigate the crosstalk between autophagy and bladder transitional cell carcinoma (TCC) by autophagy-related long noncoding RNAs (lncRNAs). A total of 400 TCC patients from The Cancer Genome Atlas were enrolled in this study. We identified the autophagy-related lncRNA expression profile of the TCC patients and then constructed a prognostic signature using the least absolute shrinkage and selection operation and Cox regression. Risk, survival, and independent prognostic analyses were carried out. Receiver operating characteristic curve, nomogram, and calibration curves were explored. Gene Set Enrichment Analysis was employed to verify the enhanced autophagy-related functions. Finally, we compared the signature with several other lncRNA-based signatures. A 9-autophagy-related lncRNA signature was established by least absolute shrinkage and selection operation-Cox regression that was significantly associated with overall survival in TCC. Among them, 8 of the 9 lncRNAs were protective factors while the remaining was a risk factor. The risk scores calculated by the signature showed significant prognostic value in survival analysis between the high- or low-risk groups. The 5-year survival rate for the high-risk group was 26.0% while the rate for the low-risk group was 56.0% (P < .05). Risk score was the only significant risk factor in the multivariate Cox regression survival analysis (P < .001). A nomogram connecting this signature with clinicopathologic characteristics was assembled. To assess the performance of the nomogram, a C-index (0.71) was calculated, which showed great convergence with an ideal model. The Gene Set Enrichment Analysis results demonstrated 2 major autophagy-related pathways were significantly enhanced in TCC. And this signature performed a similar predictive effect as other publications. The crosstalk between autophagy and TCC is significant, and this 9 autophagy-related lncRNA signature is a great predictor of TCC.

A MnAl double adjuvant nanovaccine to induce strong humoral and cellular immune responses.

At present, the most widely used aluminum adjuvants have poor ability to induce effective Th1 type immune responses. Existing evidence suggests that manganese is a potential metal adjuvant by activating cyclic guanosine phospho-adenosine synthase (cGAS)-interferon gene stimulator protein (STING) signaling pathway to enhance humoral and cellular immune response. Hence, the effective modulation of metal components is expected to be a new strategy to improve the efficiency of vaccine immunization. Here, we constructed a manganese and aluminum dual-adjuvant antigen co-delivery system (MnO2-Al-OVA) to enhance the immune responses of subunit vaccines. Namely, the aluminum hydroxide was first fused on the surface of the pre-prepared MnO2 nanoparticles, which were synthesized by a simple redox reaction with potassium permanganate (KMnO4) and oleic acid (OA). The engineered MnO2-Al-OVA could remarkably promote cellular internalization and maturation of dendritic cells. After subcutaneous vaccination, MnO2-Al-OVA rapidly migrated into the lymph nodes (LNs) and efficiently activate the cGAS-STING pathway, greatly induced humoral and cellular immune responses. Of note, our findings underscore the importance of coordination manganese adjuvants in vaccine design by promoting the activation of the cGAS-STING-IFN-I pathway. With a good safety profile and facile preparation process, this dual-adjuvant antigen co-delivery nanovaccine has great potential for clinical translation prospects.

Structure Composition and Intracellular Transport of Clathrin-Mediated Intestinal Transmembrane Tight Junction Protein.

Tight junctions (TJs) are located in the apical region of the junctions between epithelial cells and are widely found in organs such as the brain, retina, intestinal epithelium, and endothelial system. As a mechanical barrier of the intestinal mucosa, TJs can not only maintain the integrity of intestinal epithelial cells but also maintain intestinal mucosal permeability by regulating the entry of ions and molecules into paracellular channels. Therefore, the formation disorder or integrity destruction of TJs can induce damage to the intestinal epithelial barrier, ultimately leading to the occurrence of various gastrointestinal diseases, such as inflammatory bowel disease (IBD), gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS). However, a large number of studies have shown that TJs protein transport disorder from the endoplasmic reticulum to the apical membrane can lead to TJs formation disorder, in addition to disruption of TJs integrity caused by external pathological factors and reduction of TJs protein synthesis. In this review, we focus on the structural composition of TJs, the formation of clathrin-coated vesicles containing transmembrane TJs from the Golgi apparatus, and the transport process from the Golgi apparatus to the plasma membrane via microtubules and finally fusion with the plasma membrane. At present, the mechanism of the intracellular transport of TJ proteins remains unclear. More studies are needed in the future to focus on the sorting of TJs protein vesicles, regulation of transport processes, and recycling of TJ proteins, etc.

Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity.

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.

Identification and verification of YBX3 and its regulatory gene HEIH as an oncogenic system: A multidimensional analysis in colon cancer.

The novel gene YBX3 is important for regulating translation and RNA catabolism and encodes a protein with a highly conserved cold-shock domain. However, its pathogenic roles across cancers (e.g., colon cancer) and its regulation remain unclear. We identified the pathogenic roles of YBX3 and its regulatory lncRNA HEIH in various cancers and investigated their effects on tumor progression in colon cancer. Methods including RNA pull-down, MS, and TMA of 93 patients, qPCR of 12 patients with diverse clinicopathologic stages, and western blotting were performed. The pancancer analysis showed that YBX3 expression varies significantly among not only cancer types but also molecular and immune subtypes of the same cancer. Furthermore, its expression in colon cancer is clinically significant, and there is an obvious negative regulatory association between HEIH and YBX3. Among various cancers, especially colon cancer, YBX3 is more related than HEIH expression to the clinical features and prognosis of subgroups. The receiver operating characteristic analysis showed that HEIH and YBX3 have similar predictive capacity in various cancers. The analysis of differentially expressed genes in colon cancer revealed that they have similar hub gene networks, indicating an oncogenic system with a strong overlap. The results also suggest that YBX3 is associated with tumor immune evasion via different mechanisms involving T-cell exclusion in different cancer types and by the tumor infiltration of immune cells. Interestingly, scRNA-seq revealed that HEIH inhibits this phenomenon. Our results also suggest that YBX3 expression is associated with immune or chemotherapeutic outcomes in various cancers, and YBX3 exhibited a higher predictive power than two of seven standardized biomarkers for response outcomes and overall survival of immune checkpoint blockade subcohorts. In colon cancer cell lines, lncRNA-HEIH and YBX3 associate. MS confirmed that YBX3 was pulled down with HEIH, and western blot showed that HEIH knockdown disinhibited YBX3. This study strongly suggests that lncRNA-HEIH/YBX3 is a pancancer immune-oncogenic system and could serve as a biomarker for diagnosis and prognosis and as a therapeutic target, especially in colon cancer.

Smart combination of aluminum hydroxide and MF59 to induce strong cellular immune responses.

As two of the most widely used adjuvants, aluminum hydroxide and the oil-in-water emulsion MF59 have their intrinsic limitations: classical aluminum gel induces only weak cellular immune responses while MF59 cannot be used as an antigen delivery system due to its poor physical interaction with antigen molecules. Herein, we combined these two adjuvants and constructed a novel nano-vaccine delivery system by inserting aluminum hydroxide into the surface of a modified MF59 nano-emulsion (AlNEs). A model antigen ovalbumin (OVA) and an immune potentiator CpG were adsorbed on the surface of AlNEs (hereinafter AlNEs-OVA-CpG) through a facile mixing step. After subcutaneous injection, AlNEs-OVA-CpG effectively drained to lymph nodes, delivered both cargos into lymph node-resident antigen presenting cells (APCs), and escaped from lysosomes into the cytoplasm, resulting in enhanced antigen cross-presentation. Finally, AlNEs-OVA-CpG induced potent antigen-specific humoral and cellular immune responses, which significantly inhibited tumor growth and prolonged mice survival in a EG7-OVA tumor model. In sum, our results suggested that AlNEs have a great prospect to induce CD8+ T cell responses for subunit antigens.

Nanoparticles with rough surface improve the therapeutic effect of photothermal immunotherapy against melanoma.

Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.

Aluminum nanoparticles deliver a dual-epitope peptide for enhanced anti-tumor immunotherapy.

Tumor peptide vaccines contain only key amino acid sequences of tumor neoantigens, and therefore can provide precise activation of immune responses. Recent research has found that short peptide vaccines restricted to MHC-I epitopes are insufficient to activate effective CD8+ T cell responses for tumor elimination, and assistance from CD4+ T cell immunity could significantly improve the therapeutic outcome. Herein, we proposed an innovative peptide vaccine strategy to simultaneously activate CD8+ and CD4+ T cell responses by combining MHC-I and MHC-II epitopes into one long peptide antigen. To further strengthen the anti-tumor immune response induced by this dual-epitope peptide, we engineered a PEG derivative (PpASE) stabilized aluminum nanoparticle for delivering the synthetic long peptides (ANLs). The synthesized nanovaccine with a diameter of ~100 nm showed good stability and enhanced antigen uptake by antigen-presenting cells (APCs). As a result, ANLs promoted the presentation of MHC-I epitope in APCs and induced stronger activation and proliferation of CD8+ T cells as compared to aluminum nanoparticle loaded with MHC-I epitope restricted peptides (ANSs). After subcutaneous vaccination, the developed nanovaccine significantly inhibited tumor growth and prolonged mouse survival in both B16-OVA and B16F10 tumor models. Finally, ANLs were also able to elevate the maturation level of human dendritic cells (DCs), showing a great possibility of clinical translation.

Single-incision plus one-port laparoscopic gastrectomy versus conventional multi-port laparoscopy-assisted gastrectomy for gastric cancer: a retrospective study.

BACKGROUND: We compared short-term perioperative outcomes after single-incision plus one-port laparoscopic gastrectomy (SILG+1) and conventional multi-port laparoscopy-assisted gastrectomy (C-LAG) for gastric cancer. METHODS: The work was conducted between August 2017 and October 2019. A total of 90 patients with early or advanced gastric cancer were retrospectively analyzed: 43 patients of which underwent SILG+1, and 47 of which underwent C-LAG, respectively. These were divided into two groups: the total gastrectomy group (SILT+1 and C-LATG) and the distal gastrectomy group (SILD + 1 and C-LADG). The demographics, tumor characteristics, postoperative outcomes, and short-term complications of all enrolled patients were summarized and statistically analyzed. RESULTS: The mean incision length in SILT+1 group was 5.40 cm shorter than that in C-LATG group (3.15 ± 0.43 vs. 8.55 ± 2.72, P < 0.001). This comparison between the SILD + 1 and the C-LADG group produced comparable results. The SILT+1 group underwent a 56.32 min longer operation than the C-LATG group (273.03 ± 66.80 vs. 216.71 ± 82.61, P = 0.0205). SILG+1 group had better postoperative visual analog scale (VAS) and cosmetic score than those of the C-LATG group (P < 0.05). There were no significant differences in preoperative demographics or 30-day postoperative complication rates between the SILG+1 and C-LAG groups. Tumor-related index, including mass size, histological type, number of retrieved lymph nodes, pathological tumor-node-metastasis (TNM) stage, and proximal and distal edges were all equivalent between the SILG+1 and the C-LAG group. CONCLUSIONS: This retrospective study demonstrates the safety and feasibility of SILG+1 with D1+ or D2 lymphadenectomy for the treatment of early and advanced gastric cancers, compared with C-LAG.

Feasibility and preliminary experience of single-incision plus one-port laparoscopic total gastrectomy with Overlap esophagojejunostomy for gastric cancer: A study of 10 cases.

Background: This study aimed to explore the feasibility and safety of single-incision plus one-port laparoscopic total gastrectomy (SITG + 1) with Overlap esophagojejunostomy (SITG + 1-Overlap) and to share preliminary experiences. Methods: This retrospective study included 10 patients with gastric cancer located in the cardia or body who underwent SITG + 1-Overlap between August 2020 and October 2021.The demographics, tumor characteristics, postoperative outcomes, and short-term complications of all the enrolled patients were summarized and statistically analyzed. Data were expressed as mean ± standard deviation (SD) if they were normally distributed. Otherwise, Median (Quartile1, Quartile3) was used. Results: In the collective perioperative data of these 10 patients who underwent radical gastrectomy, the median of the length of transumbilical incision and blood loss were 3.0 cm and 100.0 ml respectively, and the mean operation time and 385.5 ± 51.6 min. Postoperative data indicated that the gastric tube was removed on 2.0 (2.0, 3.0) days, and the timing of first feeding, activity, flatus, and defecation was 1.5 (1.0, 2.0) days, 2.0 (2.0, 2.0) days, 3.0 (2.0, 3.0) days, and 3.8 ± 0.6 days, respectively. The timing of drainage tube removal was 4.6 ± 1.0 days after operation. The duration of hospital stay was 7.5 ± 1.2 days and the VAS pain scores for the 3 days following surgery were 3.0 (2.0, 3.3), 2.0 (2.0, 3.0), and 1.5 (1.0, 2.0) respectively. The mean number of retrieved lymph nodes was 30.7 ± 13.2. Most biochemical indicators gradually normalized with the recovery of the patients after surgery. No 30-day postoperative complications were noted. Conclusions: For the first time, our preliminary data indicate the feasibility and safety of Overlap esophagojejunostomy in SITG + 1 surgery. This modified Overlap procedure has the potential to simplify the reconstruction procedure and lower the technical challenge of SITG + 1 radical gastrectomy for cardia or upper gastric cancer in the early and advanced stages.

Tumor Antigen-Based Nanovaccines for Cancer Immunotherapy: A Review.

As an important means of tumor immunotherapy, tumor vaccines have achieved exciting results in the past few decades. However, there are still many obstacles that hinder tumor vaccines from achieving maximum efficacy, including lack of tumor antigens, low antigen immunogenicity and poor delivery efficiency. To overcome these challenges, researchers have developed and investigated various new types of tumor antigens with higher antigenic specificity and broader antigen spectrum, such as tumor-specific peptide antigens, tumor lysates, tumor cell membrane, tumor associated exosomes, etc. At the same time, different nanoparticulate delivery platforms have been developed to increase the immunogenicity of the tumor antigens, for example by increasing their targeting efficiency of antigen-presenting cells and lymph nodes, and by co-delivering antigens with adjuvants. In this review, we summarized different types of the tumor antigens that have been reported, and introduced several nanovaccine strategies for increasing the immunogenicity of tumor antigens. The review of recent progress in these fields may provide reference for the follow-up studies of tumor antigen-based cancer immunotherapy.