Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes by PKCα-associated signalling under cholesterol stimulation.

BACKGROUND AND AIMS: The secretion of bile salts transported by the bile salt export pump (BSEP) is the primary driving force for the generation of bile flow; thus, it is closely related to the formation of cholesterol stones. Caveolin-1 (Cav-1), an essential player in cell signalling and endocytosis, is known to co-localize with cholesterol-rich membrane domains. This study illustrates the role of Cav-1 and BSEP in cholesterol stone formation. METHODS: Adult male C57BL/6 mice were used as an animal model. HepG2 cells were cultured under different cholesterol concentrations and BSEP, Cav-1, p-PKCα and Hax-1 expression levels were determined via Western blotting. Expression levels of BSEP and Cav-1 mRNA were detected using real-time PCR. Immunofluorescence and immunoprecipitation assays were performed to study BSEP and Hax-1 distribution. Finally, an ATPase activity assay was performed to detect BSEP transport activity under different cholesterol concentrations in cells. RESULTS: Under low-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels significantly increased, PKCα phosphorylation significantly decreased, BSEP binding capacity to Hax-1 weakened, and BSEP function increased. Under high-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels decreased, PKCα phosphorylation increased, BSEP binding capacity to Hax-1 rose, and BSEP function decreased. CONCLUSION: Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes via PKCα-associated signalling under cholesterol stimulation.

The value of pupillary diameter in evaluating pain perception after awakening in patients undergoing general anesthesia during orthopedic surgery.

BACKGROUND: The pupillary response to tetanic electrical stimulation reflects the balance between nociceptive stimulation and analgesia. Although pupillary pain index (PPI) was utilized to predict postoperative pain, it depended on tetanic stimulation and was complex. We aim to describe the potential relationship between PD in the presence of surgical stimulation and pain levels after awakening. METHODS: According to the Verbal Rating Scale (VRS) score after extubation, the patients were divided into painless group (VRS = 0) and pain group (VRS ≥ 1). Pupillary diameter (PD) and pupillary light reflex velocity (PLRV) were compared between two groups when patients entered the operating room (T1), before incision (T2), 10 s after incision (T3), 30 s after incision (T4), 1 h after incision (T5), at the end of surgery (T6), shortly after extubation (T7), and when patients expressed pain clearly (T8). The magnitude of PD change (ΔPD) compared to the baseline value after anesthesia induction (T2) was calculated. The correlations between pupillary parameters and pain after awakening were calculated. RESULTS: Patients with VRS ≥ 1 had greater PD than painless patients at T3-7 (P = 0.04, 0.04, 0.003, <0.001, <0.001), and it was positively correlated with VRS score after awakening at T4-7 (r = 0.188, 0.217, 0.684, 0.721). The ability of T6ΔPD to predict VRS ≥ 1 was strong [threshold: 20.53%, area under the curve (AUC): 0.93, 95% confidence interval (CI): 0.89-0.97 ]. CONCLUSION: Our study indicates that PD is a useful index to direct the individualized analgesics used during operation, to better avoid the occurrence of pain during the postoperative emergence period. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2000040908, registration date: 15/12/2020).

Peptide vaccine from cancer-testis antigen ODF2 can potentiate the cytotoxic T lymphocyte infiltration through IL-15 in non-MSI-H colorectal cancer.

About 85% of patients with colorectal cancer (CRC) have the non-microsatellite instability-high (non-MSI-H) subtype, and many cannot benefit from immune checkpoint blockade. A potential reason for this is that most non-MSI-H colorectal cancers are immunologically "cold" due to poor CD8+ T cell infiltration. In the present study, we screened for potential cancer-testis antigens (CTAs) by comparing the bioinformatics of CD8+ T effector memory (Tem) cell infiltration between MSI-H and non-MSI-H CRC. Two ODF2-derived epitope peptides, P433 and P609, displayed immunogenicity and increased the proportion of CD8+ T effector memory (Tem) cells in vitro and in vivo. The adoptive transfer of peptide pool-induced CTLs inhibited tumor growth and enhanced CD8+ T cell infiltration in tumor-bearing NOD/SCID mice. The mechanistic study showed that knockdown of ODF2 in CRC cells promoted interleukin-15 expression, which facilitated CD8+ T cell proliferation. In conclusion, ODF2, a CTA, was negatively correlated with CD8+ T cell infiltration in "cold" non-MSI-H CRC and was selected based on the results of bioinformatics analyses. The corresponding HLA-A2 restricted epitope peptide induced antigen-specific CTLs. Immunotherapy targeting ODF2 could improve CTA infiltration via upregulating IL-15 in non-MSI-H CRC. This tumor antigen screening strategy could be exploited to develop therapeutic vaccines targeting non-MSI-H CRC.

Comparison of Efficacy and Safety between Endoscopic Retrograde Cholangiopancreatography and Percutaneous Transhepatic Cholangial Drainage for the Treatment of Malignant Obstructive Jaundice: A Systematic Review and Meta-Analysis.

BACKGROUND: At present, endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangial drainage (PTCD) are frequently used for reducing malignant obstructive jaundice (MOJ). However, it is controversial as to which method is superior in terms of efficacy and safety. OBJECTIVES: The aim of this study was to compare the safety, feasibility, and clinical benefits of ERCP and PTCD in matched cases of MOJ. METHODS: The Web of Science, Cochrane, PubMed, and CNKI databases were searched systematically to identify studies published between January 2000 and December 2019, without language restrictions, that compared ERCP and PTCD in patients with MOJ. The primary outcome was the success rate for each procedure. The secondary outcomes were the technical success rate, serum total bilirubin level, length of hospital stay, hospital expense, complication rate, and survival. This meta-analysis was performed using Review Manager 5.3. RESULTS: Sixteen studies met the inclusion criteria, including 1,143 cases of ERCP and 854 cases of PTCD. The analysis demonstrated that jaundice remission in PTCD was equal to that in ERCP (mean difference [MD], 1.19; 95% confidence interval [CI]: -0.56 to -2.93; p = 0.18). However, the length of hospital stay in the ERCP group was 3.03 days shorter than that in the PTCD group (MD, -2.41; 95% CI: -4.61 to -0.22; p = 0.03). ERCP had a lower rate of postoperative complications (odds ratio, 0.66; 95% CI: 0.42-1.05); however, the difference was not significant (p = 0.08). ERCP was also more cost-efficient (MD, -5.42; 95% CI: -5.52 to -5.32; p < 0.01). Further, we calculated the absolute mean of hospital stay (ERCP:PTCD = 8.73:12.95 days), hospital expenses (ERCP:PTCD = 5,104.13:5,866.75 RMB), and postoperative complications (ERCP:PTCD = 11.2%:9.1%) in both groups. CONCLUSION: For remission of MOJ, PTCD and ERCP had similar clinical efficacy. Each method has its own strengths and weaknesses. Considering that ERCP had a lower rate of postoperative complications, shorter hospital stay, and higher cost efficiency, ERCP may be a superior initial treatment choice for MOJ.

Identification of Stopping Points in GPS Trajectories by Two-Step Clustering Based on DPCC with Temporal and Entropy Constraints.

The widespread adoption of intelligent devices has led to the generation of vast amounts of Global Positioning System (GPS) trajectory data. One of the significant challenges in this domain is to accurately identify stopping points from GPS trajectory data. Traditional clustering methods have proven ineffective in accurately identifying non-stopping points caused by trailing or round trips. To address this issue, this paper proposes a novel density peak clustering algorithm based on coherence distance, incorporating temporal and entropy constraints, referred to as the two-step DPCC-TE. The proposed algorithm introduces a coherence index to integrate spatial and temporal features, and imposes temporal and entropy constraints on the clusters to mitigate local density increase caused by slow-moving points and back-and-forth movements. Moreover, to address the issue of interactions between subclusters after one-step clustering, a two-step clustering algorithm is proposed based on the DPCC-TE algorithm. Experimental results demonstrate that the proposed two-step clustering algorithm outperforms the DBSCAN-TE and one-step DPCC-TE methods, and achieves an accuracy of 95.49% in identifying stopping points.

Role of caveolin-1 in human organ function and disease: friend or foe?

Caveolin-1 (Cav-1) is a structural protein component of caveolae, which are invaginations of the plasma membrane involved in various cellular processes, including endocytosis, extracellular matrix organization, cholesterol distribution, cell migration and signaling. Mounting evidence over the last 10-15 years has demonstrated a central role of Cav-1 in many diseases, such as cancer, diabetes and fibrosis. Cav-1 plays positive and negative roles in various diseases through its different regulation pathways. Here, we review the current knowledge on Cav-1 in different diseases and discuss the role of this protein in human organs and diseases.

Advances in the Study of Acute Acalculous Cholecystitis: A Comprehensive Review.

BACKGROUND: Acute acalculous cholecystitis (AAC) is characterized by acute necrotizing inflammation with no calculi and is diagnosed based on imaging, intraoperative, and pathological examinations. KEY MESSAGE: Although AAC has been studied clinically for a long time, it remains difficult to diagnose and treat. The pathogenesis of AAC is still not fully understood, and it is often regarded as a relatively independent clinical disease that is different from acute calculous cholecystitis (ACC). Pathological studies suggest that AAC is the manifestation of a critical systemic disease, while ACC is a local disease of the gallbladder. SUMMARY: Concerning the pathogenesis, diagnosis, and treatment of AAC, we reviewed the research progress of AAC, which will enhance the understanding of the early diagnosis and treatment of AAC.

Influence of Abdominal Aortic Calcification on the Distal Extent and Branch Blood Supply of Acute Aortic Dissection.

BACKGROUND: This study aimed to investigate the influence of abdominal aortic calcification on the distal extent, blood supply, and mid-term outcomes of acute aortic dissection (AAD). METHODS: This single-centre retrospective study was conducted from August 2014 to May 2021. The aortic calcification index was used to evaluate abdominal aortic calcification. The standardized method provided by the Society for Vascular Surgery was used to evaluate the distal extent of AAD. Patients were divided into 3 groups as per the degree of calcification: no calcification (NC), low calcification (LC), and high calcification (HC). RESULTS: In a cohort of 723 patients, abdominal aortic calcification was present in 424 (58.6%) patients. The prevalence of coronary heart disease increased with the degree of calcification (NC versus LC versus HC: 8.4% vs. 9.5% vs. 19.3%, P < 0.001). The aortic calcification index of the distal extent at zone 9 was higher than that of the distal extent exceeding zone 9 (P = 0.001). The proportions of the NC, LC, and HC groups with distal extents exceeding zone 9 were 65.9% vs. 56.2% vs. 37.7%, P < 0.001. In a multivariate logistics analysis, the calcification grade was a protective factor of distal extents exceeding zone 9 (P < 0.001, odds ratio [OR] = 0.592). Hypertension (P = 0.019, OR = 1.559) and D-dimer (P < 0.001, OR = 1.045) were risk factors. There was a higher proportion of branch-vessels on the abdominal aorta supplied by the true lumen in the calcification group (NC versus LC versus HC: 27.8% vs. 43.8% vs. 51.1%, P < 0.001). There were no significant differences in the mid-term outcomes among the groups. CONCLUSIONS: Abdominal aortic calcification could limit the distal extent in patients with AAD and increase the proportion of branch-vessels on the abdominal aorta supplied by the true lumen.

Dilemma of the differential diagnosis of hilar cholangiocarcinoma and benign diseases: a single-center retrospective study.

Hilar cholangiocarcinoma (HCCA), which lacks specific clinical manifestations, remains very difficult to distinguish from benign disease. This distinction is further complicated by the complex hilar anatomy. We conducted the present study to evaluate the differential diagnosis of these conditions. Sixty-five patients underwent resection surgery for suspected HCCA between January 2011 and October 2018. Institutional Review Board of Shengjing hospital agreed this study and all participants sign an informed consent document prior to participation in a research study. Following a postoperative pathology analysis, all patients were divided into two groups: malignant group (54 patients with HCCA) and benign group (11 cases with benign lesions). Compared with the benign group, the malignant group had a significantly higher median age and serum CA19-9, CEA, ALT, BILT and BILD levels (P < 0.05). In contrast, the groups did not differ significantly in terms of the sex distribution, clinical manifestations, serum levels of AST and ALKP, and imaging findings. In a receiver operating characteristic curve analysis, we identified a CA19-9 cutoff point of 233.15 U/ml for the differential diagnosis and CEA cutoff point of 2.98 ng/ml for the differential diagnosis. The differential diagnosis of HCCA and benign hilar lesions remains difficult. However, we found that patients with HCCA tended to have an older age at onset and higher serum levels of CA19-9, CEA, BILT, ALT and BILD. Furthermore, patients with a serum CA19-9 level >233.15 U/ml and CEA level >2.98 ng/ml are more likely to have malignant disease.

Laparoscopic transcystic common bile duct exploration (LTCBDE): a safer method to treat common bile duct stones than laparoscopic choledochotomy.

We read the article published in the Spanish Journal of Gastroenterology and its accompanying editorial about the laparoscopic treatment of both cholecystolithiasis and choledocholithiasis in a single stage procedure. We would like to make some comments. Common bile duct (CBD) stones can lead to serious complications such as cholangitis and pancreatitis. So far, there is no standard surgical treatment for choledocholithiasis. Although, there are some ways to deal with CBD stones. Each method has its own advantages and disadvantages. In the era of advancements in minimally invasive technology, the treatment of CBD stones still remains controversial with regard to endoscopic retrograde cholangiopancreatography (ERCP) or laparoscopic common bile duct exploration (LCBDE). Preoperative ERCP followed by laparoscopic cholecystectomy (LC) is frequently performed.

Hepatic hilar mass in an adolescent: a rare case of hepatobiliary tuberculosis.

BACKGROUND: Hepatobiliary tuberculosis is a rare manifestation of Mycobacterium tuberculosis infection, especially in younger patients. The non-specific symptoms and signs as well as the lack of definite imaging characteristics often impedes diagnosis. Definite diagnosis of tuberculosiscan be obtained through histopathological examination; conventional anti-tuberculosis drugs and surgery are the most commonly recommended treatments. CASE PRESENTATION: A previously healthy 15-year-old rural adolescent male presented with a 2-month history of weight loss and fatigue. We strongly suspected a Klatskin tumor; therefore, exploratory laparotomy was performed. However, the microscopical findings revealed a granuloma consisting of epithelioid cells, caseous necrosis, and lymphocytic infiltration, indicating caseating granulomatous inflammation and yielding a final diagnosis of hepatic hilar tuberculosis. CONCLUSION: Hepatic hilar tuberculosis is an extremely rare case; few physicians may have actually treated a case. This report therefore aims to improve the overall understanding of lymphatic tuberculosis of the hepatic hilum.

Clip-stone and T clip-sinus: A clinical analysis of six cases on migration of clips and literature review from 1997 to 2017.

INTRODUCTION: With the development of laparoscopic skills, the laparoscopic common bile duct exploration (LCBDE) and laparoscopic cholecystectomy (LC) has become the standard surgical procedure for choledocholithiasis. We usually use Hem-o-lok clips to control cystic duct and vessels, which is safe on most occasions and has few perioperative complications such as major bleeding, wound infection, bile leakage, and biliary and bowel injury. However, a rare complication of post-cholecystectomy clip migration (PCCM) increases year by year due to the advancement and development of LC, CBD exploration as well as the wide use of surgical ligation clips. MATERIALS AND METHODS: Six patients whose clips are found dropping into CBD or forming T-tube sinus after laparoscopic surgery in our department. RESULTS: Six patients whose clips are found dropping into CBD (clip-stone) (3/6) or forming T-tube sinus (T clip-sinus) (3/6) after LCBDE or LC. CONCLUSIONS: PCCM is a rare but severe complication of LCBDE. A pre-operative understanding of bile duct anatomy, the use of the minimum number of clips and the harmonic scalpel during the surgeries is necessary. Considering clip-stone or clip-sinus in the differential diagnosis of patients with biliary colics or cholangitis after LCBDE even years after surgery, the detailed medical history and pre-operative examination are inevitable, especially for these patients who had undergone LCBDE.

Transcystic versus traditional laparoscopic common bile duct exploration: its advantages and a meta-analysis.

BACKGROUND: The best approach for treating common bile duct stones remains a matter of debate. Traditional laparoscopic common bile duct exploration (LCBDE) can cause adverse events such as stenosis of the bile duct. Moreover, with advances in technology and surgical skills, the use of laparoscopic transcystic common bile duct exploration (LTCBDE) is gradually rising. OBJECTIVES: To compare the safety, feasibility, and short-term clinical benefits of LTCBDE and LCBDE through matched cases. METHODS: Web of science, Cochrane, PubMed, and CNKI were searched systematically to identify studies published between January 2007 and December 2017 that compared LTCBDE and LCBDE without a restriction of languages. This meta-analysis was performed using Review Manager 5.3. RESULTS: Twenty-one studies matched the selection criteria, including 1561 cases of LTCBDE and 1500 cases of LCBDE. There was no obvious difference in stone clearance (OR 1.44, 95% CI 0.84-2.47; P = 0.18). However, LTCBDE had a shorter operative time (MD - 17.72, 95% CI - 19.42 to - 16.02; P < 0.00001) and shorter hospital stay (MD - 2.20, 95% CI - 2.32 to - 2.08; P < 0.00001). Besides, the LTCBDE group showed significantly better results for blood loss (MD - 7.61, 95% CI - 8.85 to - 6.37; P < 0.00001) and postoperative complications (OR 0.28, 95% CI 0.19-0.41; P < 0.00001). In addition, LTCBDE was more cost efficient (MD - 2.51, 95% CI - 2.72 to - 2.30; P < 0.00001). Further, we calculated the absolute mean of operative time (LTCBDE:LCBDE = 97.56:117.81 min), hospital stay (LTCBDE:LCBDE = 5.22:8.91 days), hospital expenses (LTCBDE:LCBDE = 8646.121:11848.31 RMB), blood loss (LTCBDE:LCBDE = 29.3:52.0 ml), the rate of CBD stone clearance (LTCBDE:LCBDE = 92.8:95.0%), and postoperative complications (LTCBDE:LCBDE = 6.7:14.6%) in both groups to obtain more convincing results. CONCLUSIONS: The stone clearance of LTCBDE was equal to that of LCBDE, and LTCBDE demonstrated a shorter operative time, lower blood loss, and other advantages. Thus, the surgical procedure of laparoscopic transcystic choledochotomy is feasible and safe.

Identification of a novel DEC-205 binding peptide to develop dendritic cell-targeting nanovaccine for cancer immunotherapy.

Cancer vaccine is regarded as an effective immunotherapy approach mediated by dendritic cells (DCs) which are crucial for antigen presentation and the initiation of adaptive immune responses. However, lack of DC-targeting properties significantly hampers the efficacy of cancer vaccines. Here, by using the phage display technique, peptides targeting the endocytic receptor DEC-205 primarily found on cDC1s were initially screened. An optimized hydrolysis-resistant peptide, hr-8, was identified and conjugated to PLGA-loaded antigen (Ag) and CpG adjuvant nanoparticles, resulting in a DC-targeting nanovaccine. The nanovaccine hr-8-PLGA@Ag/CpG facilitates dendritic cell maturation and improves antigen cross-presentation. The nanovaccine can enhance the antitumor immune response mediated by CD8+ T cells by encapsulating the nanovaccine with either exogenous OVA protein antigen or endogenous gp100/E7 antigenic peptide. As a result, strong antitumor effects are observed in both anti-PD-1 responsive B16-OVA and anti-PD-1 non-responsive B16 and TC1 immunocompetent tumor models. In summary, this study presents the initial documentation of a nanovaccine that targets dendritic cells via the novel DEC-205 binding peptide. This approach offers a new method for developing cancer vaccines that can potentially improve the effectiveness of cancer immunotherapy.

Traumatic Aortic Dissection as a Unique Clinical Entity: A Single-Center Retrospective Study.

BACKGROUND: This study aimed to compare the clinical characteristics, treatment approaches, and outcomes of the Stanford Type B traumatic aortic dissection (TAD) with non-traumatic aortic dissection (NTAD), and assess better management for TAD. METHODS: We retrospectively analyzed patients who underwent thoracic endovascular aortic repair for Stanford type B aortic dissection at The First Hospital of China Medical University between 2014 and 2022. The patients were divided into TAD and NTAD groups based on whether they had a history of acute trauma. This study ultimately included 65 patients with TAD and 288 with NTAD. We assessed and compared the baseline characteristics, laboratory indicators, imaging features, surgical procedures, and follow-up results between the groups. RESULTS: The TAD group was younger compared to the NTAD group (50.00 [IQR40.00-59.00] vs. 55.00 [IQR 47.00-61.00] years, p = 0.020). A lower percentage of the TAD group had a history of hypertension (20% vs. 71.18%, p < 0.001). The length of aortic dissection was shorter in the TAD group compared to the NTAD group (30.00 [IQR 22.00-40.00] vs. 344.00 [IQR 237.25-400.00] mm, p < 0.001). All patients with TAD underwent TEVAR following the same strategy as NTAD. The mean preoperative duration was 7.00 (IQR 2.00-14.00) days in the TAD group and 11.00 (IQR 8.00-15.00) days in the NTAD group (p < 0.001). TAD showed fewer complications after TEVAR in mid-to-long-term follow-up. CONCLUSIONS: TAD is distinct from NTAD. TAD typically presents with more localized lesions than NTAD, and the patients experience a shorter preoperative duration and a better mid-to-long-term outcome.

Effectiveness and safety of central pancreatectomy in benign or low-grade malignant pancreatic body lesions: a systematic review and meta-analysis.

BACKGROUND: The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and distal pancreatectomy (DP) are associated with a risk of impairment of pancreatic function at long-term follow-up. With advances in technology and surgical skills, the use of central pancreatectomy (CP) has gradually increased. OBJECTIVES: The objective was to compare the safety, feasibility, and short-term and long-term clinical benefits of CP and DP in matched cases. METHODS: The PubMed, MEDLINE, Web of Science, Cochrane, and EMBASE databases were systematically searched to identify studies published from database inception to February 2022 that compared CP and DP. This meta-analysis was performed using R software. RESULTS: Twenty-six studies matched the selection criteria, including 774 CP and 1713 DP cases. CP was significantly associated with longer operative time ( P <0.0001), less blood loss ( P <0.01), overall and clinically relevant pancreatic fistula ( P <0.0001), postoperative hemorrhage ( P <0.0001), reoperation ( P =0.0196), delayed gastric emptying ( P =0.0096), increased hospital stay ( P =0.0002), intra-abdominal abscess or effusion ( P =0.0161), higher morbidity ( P <0.0001) and severe morbidity ( P <0.0001) but with a significantly lower incidence of overall endocrine and exocrine insufficiency ( P <0.01), and new-onset and worsening diabetes mellitus ( P <0.0001) than DP. CONCLUSIONS: CP should be considered as an alternative to DP in selected cases such as without pancreatic disease, length of the residual distal pancreas is more than 5 cm, branch-duct intraductal papillary mucinous neoplasms, and a low risk of postoperative pancreatic fistula after adequate evaluation.

Laparoscopic surgery for gallstones or common bile duct stones: A stably safe and feasible surgical strategy for patients with a history of upper abdominal surgery.

Backgrounds/Aims: A history of upper abdominal surgery has been identified as a relative contraindication for laparoscopy. This study aimed to compare the clinical efficacy and safety of laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) in patients with and without previous upper abdominal surgery. Methods: In total, 131 patients with previous upper abdominal surgery and 64 without upper abdominal surgery underwent LC or LCBDE between September 2017 and September 2021 at the Shengjing Hospital of China Medical University. Patients with previous upper abdominal surgery were divided into four groups: group A included patients with previous right upper abdominal surgery who underwent LC (n = 17), group B included patients with previous other upper abdominal surgery who underwent LC (n = 66), group C included patients with previous right upper abdominal surgery who underwent LCBDE (n = 30), and group D included patients with previous other upper abdominal surgery who underwent LCBDE (n = 18). Patient demographics and perioperative outcomes were retrospectively analyzed. Results: The preoperative liver function indexes showed no significant difference between the observation and control groups. For patients who underwent LC, groups A and B had more abdominal adhesions than the control group. One case was converted to open surgery in each of groups A and B. There was no statistical difference in operation time, estimated blood loss, postoperative hospital stay, and drainage volume. For patients who underwent LCBDE, groups C and D had more estimated blood loss than the control group (group C, 41.33 ± 50.84 vs. 18.97 ± 13.12 ml, p = 0.026; group D, 66.11 ± 87.46 vs. 18.97 ± 13.12 ml, p = 0.036). Compared with the control group, group C exhibited longer operative time (173.87 ± 60.91 vs. 138.38 ± 57.38 min, p = 0.025), higher drainage volume (296.83 ± 282.97 vs. 150.83 ± 127.04 ml, p = 0.015), and longer postoperative hospital stay (7.97 ± 3.68 vs. 6.17 ± 1.63 days, p = 0.021). There was no mortality in all groups. Conclusions: LC or LCBDE is a safe and feasible procedure for experienced laparoscopic surgeons to perform on patients with previous upper abdominal surgery.

Screening and identification of HLA-A2-restricted neoepitopes for immunotherapy of non-microsatellite instability-high colorectal cancer.

Colorectal cancer has one of the highest mortality rates among malignant tumors, and most patients with non-microsatellite instability-high (MSI-H) colorectal cancer do not benefit from targeted therapy or immune checkpoint inhibitors. Identification of immunogenic neoantigens is a promising strategy for inducing specific antitumor T cells for cancer immunotherapy. Here, we screened potential high-frequency neoepitopes from non-MSI-H colorectal cancer and tested their abilities to induce tumor-specific cytotoxic T cell responses. Three HLA-A2-restricted neoepitopes (P31, P50, and P52) were immunogenic and could induce cytotoxic T lymphocytes in peripheral blood mononuclear cells from healthy donors and colorectal cancer patients. Cytotoxic T lymphocytes induced in HLA-A2.1/Kb transgenic mice could recognize and lyse mutant neoepitope-transfected HLA-A2+ cancer cells. Adoptive transfer of cytotoxic T lymphocytes induced by the peptide pool of these three neoepitopes effectively inhibited tumor growth and increased the therapeutic effects of anti-PD-1 antibody. These results revealed the potential of high-frequency mutation-specific peptide-based immunotherapy as a personalized treatment approach for patients with non-MSI-H colorectal cancer. The combination of adoptive T cell therapy based on these neoepitopes with immune checkpoint inhibitors, such as anti-PD-1, could provide a promising treatment strategy for non-MSI-H colorectal cancer.

Osthole: An up-to-date review of its anticancer potential and mechanisms of action.

With its high incidence and mortality rates, cancer is one of the largest health problems worldwide. Investigating various cancer treatment options has been the focus of many domestic and international researchers, and significant progress has been made in the study of the anticancer effects of traditional Chinese medicines. Osthole, a coumarin compound extracted from Cnidium monnieri (L.) Cuss., has become a new research hotspot. There have been many reports on its anticancer effects, and recent studies have elucidated that its underlying mechanism of action mainly involves inhibiting cancer cell proliferation, inducing cancer cell apoptosis, inhibiting invasion and migration of cancer cells, inhibiting cancer angiogenesis, increasing sensitivity to chemotherapy drugs, and reversing multidrug resistance of cancer cells. This mini-review summarizes the research progress on the anticancer effects of osthole in recent years.