Radical resection in a patient with stage IIIA non-small cell lung cancer with the EGFR exon 19 deletion mutation after neoadjuvant targeted therapy with osimertinib: a case report.

Background: With the advent of targeted therapies, the survival rates of patients with locally advanced lung cancer have significantly improved. However, there is limited research on the efficacy of neoadjuvant targeted therapy in resectable advanced non-small cell lung cancer (NSCLC) patients with positive driver genes. This article reports a case of stage IIIA NSCLC with an epidermal growth factor receptor (EGFR) 19del mutation that successfully underwent radical lung cancer surgery following neoadjuvant targeted therapy. By observing the perioperative treatment outcomes and side effects in this patient, we aimed to provide insights and summarize experiences for treating similar cases in the future. Case Description: We report a case of a 54-year-old female diagnosed preoperatively with stage IIIA adenocarcinoma of the left upper lung (cT1cN2M0). The patient's course was complicated by acute sick sinus syndrome and was cured by implanting a permanent pacemaker. After multidisciplinary discussion, it was decided to administer neoadjuvant targeted therapy with osimertinib. Following 6 weeks of treatment, the tumor assessment showed partial response (PR), making the patient eligible for surgery. The patient underwent single-port thoracoscopic left upper lobectomy + mediastinal lymphadenectomy. Intraoperatively, the left hilar lymph nodes were found to be tightly adherent to the apical-anterior branch of the left upper pulmonary artery. The main trunk of the left pulmonary artery was temporarily occluded with a vascular clamp to safely dissect the left upper pulmonary artery. The procedure was completed without conversion to open thoracotomy, achieving an R0 resection. Postoperative pathology confirmed stage IIIA (ypT1bN2M0), and the patient continued adjuvant therapy with osimertinib. Conclusions: Neoadjuvant targeted therapy with osimertinib is expected to become one of the options for neoadjuvant therapy in locally advanced NSCLC with sensitizing EGFR mutations. And for those with advanced lung cancer involving tumors close to the hilum or mediastinal lymph node metastasis, preblocking of the left upper pulmonary artery can help improve surgical safety and better ensure R0 resection.

"Multidisciplinary fast-track" care can significantly reduce risk of mortality among hip fracture patients at least 80 years old: a single-center retrospective study.

BACKGROUND: "Multidisciplinary fast-track" (MFT) care can accelerate recovery and improve prognosis after surgery, but whether it is effective in older people after hip fracture surgery is unclear. METHODS: We retrospectively compared one-year all-cause mortality between hip fracture patients at least 80 years old at our institution who underwent hip fracture surgery between January 2014 and December 2018 and who then received MFT or conventional care. Multivariable regression was used to assess the association between MFT care and mortality after adjustment for confounders. RESULTS: The final analysis included 247 patients who received MFT care and 438 who received conventional orthopedic care. The MFT group showed significantly lower one-year mortality (8.9% vs. 14.4%, P = 0.037). Log-rank testing of Kaplan-Meier survival curves confirmed the survival advantage. However, the two groups did not differ significantly in rates of mortality during hospitalization or at 30 or 90 days after surgery. Regression analysis confirmed that MFT care was associated with lower risk of one-year mortality (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.281-0.788, P = 0.04), and the survival benefit was confirmed in subgroups of patients with anemia (HR 0.453, 95% CI 0.268-0.767, P = 0.003) and patients with American Society of Anesthesiologists grade III (HR 0.202, 95% CI 0.08-0.51, P = 0.001). CONCLUSIONS: MFT care can reduce one-year mortality among hip fracture patients at least 80 years old. This finding should be verified and extended in multi-center randomized controlled trials.

Three-Dimensional Reconstruction Computed Tomography in Thoracoscopic Segmentectomy: A Randomized Controlled Trial.

OBJECTIVES: Thoracoscopic segmentectomy is the recommended treatment option for small peripheral pulmonary nodules. To assess the ability of preoperative 3D reconstruction CT to shorten the operative time and improve perioperative outcomes in thoracoscopic segmentectomy compared with standard chest CT, we conducted this randomized controlled trial. METHODS: The DRIVATS study was a multicentre, randomized controlled trial conducted in three hospitals between July 2019 and November 2023. Patients with small peripheral pulmonary nodules not reaching segments borders were randomized in a 1:1 ratio to receive either 3D reconstruction CT or standard chest CT before thoracoscopic segmentectomy. The primary end-point was operative time. The secondary end-points included incidence of postoperative complications, intraoperative blood loss and operative accident event. RESULTS: A total of 191 patients were enrolled in this study: 95 in the 3D reconstruction CT group and 96 in the standard chest CT group. All patients underwent thoracoscopic segmentectomy except for one patient in the standard chest CT group who received a wedge resection. There is no significant difference in operative time between the 3D reconstruction CT group (median, 100 min [IQR, 85-120]) and the standard chest CT group (median, 100 min [IQR, 81-140]) (P = 0.82). Only one intraoperative complication occurred in the standard chest CT group. No significant difference was observed in the incidence of postoperative complications between the two groups (P = 0.52). Other perioperative outcomes were also similar. CONCLUSIONS: In patients with small peripheral pulmonary nodules not reaching segments borders, the use of 3D reconstruction CT in thoracoscopic segmentectomy was feasible, but it did not result in significant differences in operative time or perioperative outcomes compared to standard chest CT.

Nutrient-delivery and metabolism reactivation therapy for melanoma.

To fulfil the demands of rapid proliferation, tumour cells undergo significant metabolic alterations. Suppression of hyperactivated metabolism has been proven to counteract tumour growth. However, whether the reactivation of downregulated metabolic pathways has therapeutic effects remains unexplored. Here we report a nutrient-based metabolic reactivation strategy for effective melanoma treatment. L-Tyrosine-oleylamine nanomicelles (MTyr-OANPs) were constructed for targeted supplementation of tyrosine to reactivate melanogenesis in melanoma cells. We found that reactivation of melanogenesis using MTyr-OANPs significantly impeded the proliferation of melanoma cells, primarily through the inhibition of glycolysis. Furthermore, leveraging melanin as a natural photothermal reagent for photothermal therapy, we demonstrated the complete eradication of tumours in B16F10 melanoma-bearing mice through treatment with MTyr-OANPs and photothermal therapy. Our strategy for metabolism activation-based tumour treatment suggests specific nutrients as potent activators of metabolic pathways.

Elevated histone deacetylase 10 expression promotes the progression of clear cell renal cell carcinoma by Notch-1-PTEN signaling axis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most common pathological subtype of kidney cancer, accounts for approximately 70% to 80% of all cases. Histone deacetylase 10 (HDAC10) belongs to the HDAC class IIb subgroup, one of the histone deacetylases (HDAC) family. Previous studies suggest that HDAC10 may regulate the development of multiple tumor types. The specific molecular mechanisms employed by HDAC10 in the etiology of ccRCC still need to be discovered. METHODS: The analysis included examining HDAC10 expression levels and their clinical importance within a cohort of inpatients and ccRCC patients documented in the Tumor Genome Atlas (TCGA). Moreover, the biological functions and underlying molecular mechanisms of HDAC10 were investigated. RESULTS: HDAC10 showed increased expression in ccRCC tumor tissues. Subsequent analysis revealed overexpression of HDAC10 was associated with advanced clinical phenotype and unfavorable prognosis. The absence of HDAC10 significantly decreased ccRCC cell proliferation and migration capabilities. Mechanistic research suggests that HDAC10 may promote RCC development by activating the Notch-1 pathway and downregulating PTEN expression levels. CONCLUSION: In summary, HDAC10 can modulate critical biological processes in ccRCC, including proliferation, migration, and apoptosis. Notably, the Notch-1 pathway and PTEN serve as crucial signaling pathways and target genes through which HDAC10 regulates the progression of ccRCC. These findings offer a novel outlook for ccRCC treatment.

Nanoparticles targeting OPN loaded with BY1 inhibits vascular restenosis by inducing FTH1-dependent ferroptosis in vascular smooth muscle cells.

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.

Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK.

The efficient clinical treatment of oral squamous cell carcinoma (OSCC) is still a challenge that demands the development of effective new drugs. Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors, however, not much is known about the influence of phenformin on OSCC cells. We found that phenformin suppresses OSCC cell proliferation, and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro. RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4 (DNA damage inducible transcript 4) and NIBAN1 (niban apoptosis regulator 1). We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy. Further, the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4 (activation transcription factor 4), which was induced by phenformin treatment in OSCC cells. Mechanistically, these results revealed that phenformin triggers endoplasmic reticulum (ER) stress to activate PERK (protein kinase R-like ER kinase), which phosphorylates the transitional initial factor eIF2, and the increased phosphorylation of eIF2 leads to the increased translation of ATF4. In summary, we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth. Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Sodium salt promoted the generation of nano zero valent iron by carbothermal reduction: For activating peroxydisulfate to degrade antibiotic.

Carbothermal reduction is a promising method for the industrial preparation of nano-zero-valent iron. Preparing it also involves very high pyrolysis temperatures, which leads to a significant amount of energy consumption. The temperature required for the preparation of nano-zero-valent iron by carbothermal reduction was reduced by 200 °C by the addition of sodium salt. Carbon-loaded nano zero-valent iron (Fe0/CB-Na) was prepared by carbothermal reduction through the addition of sodium salt. The results showed that Fe0/CB-Na@700 had the same activation performance as Fe0/CB@900 and the newly prepared nano-zero-valent iron. The addition of sodium salt promoted the transfer of oxygen from the iron oxide to the carbon structure during the roasting process so that the iron oxide was reduced to as much Fe0 as possible. Thus, sodium salts were optimized for the preparation of nano-zero-valent iron by carbothermal reduction through interfacial amorphization and oxygen transfer, thus reducing the preparation cost.

Single-port video-assisted thoracoscopic sleeve lobectomy after neoadjuvant immunochemotherapy: a case report.

Background: The morbidity and mortality of lung cancer have always ranked first among malignant tumors (MTs). Previous studies have shown that neoadjuvant chemotherapy can improve the 5-year survival rate of patients with non-small cell lung cancer (NSCLC), but the benefit is limited. Studies have proven that neoadjuvant immunotherapy combined with chemotherapy has unique advantages in prolonging patient survival, reducing distant recurrence, and inducing antitumor immunity. However, its impact remains to be more comprehensively investigated. Case Description: A 59-year-old male who was admitted to the hospital with a primary complaint of repeated cough and expectoration for 6 months. Preoperative assessment showed right upper lung squamous cell carcinoma with multiple hilar and mediastinal lymph node metastasis, and the clinical stage was cT2aN2M0 stage (IIIA). After three cycles of pembrolizumab + carboplatin + paclitaxel therapy were administered, the reexamination of the tumor was evaluated as partial response (PR), and a sleeve lobectomy of the right upper lung was performed under single-port thoracoscopic surgery. The operation proceeded smoothly without conversion to thoracotomy, and R0 resection was successfully achieved. Postoperative pathological stage was ypT1bN0M0 stage IA, and postoperative pathological remission was evaluated as major pathological response (MPR). After the operation, three cycles of immunotherapy combined with chemotherapy were completed, which was followed by maintenance therapy with pembrolizumab monotherapy for 1 year, and no signs of tumor recurrence and metastasis have been found in follow-up thus far. Conclusions: Through this case, we believe that for locally advanced NSCLC sleeve lobectomy after neoadjuvant therapy may be a safe and feasible treatment option, can avoid pneumonectomy, protect the lung function of patients, and still ensure the R0 resection rate. Moreover, it may does not significantly increase the difficulty of surgical operation or reduce safety. However, further research is needed to confirm our conclusion. And then, neoadjuvant therapy in the perioperative period may induce a series of side effects or adverse reactions, and thus greater attention should be paid to its timely management.

Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning.

BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are important prognostic factors for gastric cancer (GC) that indicate an increased risk of metastasis and poor outcomes. Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment decisions. However, prior models using conventional computed tomography (CT) images to predict LVI or PNI separately have had limited accuracy. Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion. We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients. AIM: To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately. METHODS: This study used a retrospective dataset involving 257 GC patients (training cohort, n = 172; validation cohort, n = 85). First, several clinical indicators, including serum tumor markers, CT-TN stages and CT-detected extramural vein invasion (CT-EMVI), were extracted, as were quantitative spectral CT parameters from the delineated tumor regions. Next, a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters. A logistic regression (LR)-based nomogram model was subsequently constructed to predict LVI/PNI status, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: In both the training and validation cohorts, CT T3-4 stage, CT-N positive status, and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant (P < 0.05). LR analysis of the training group showed preoperative CT-T stage, CT-EMVI, single-energy CT values of 70 keV of venous phase (VP-70 keV), and the ratio of standardized iodine concentration of equilibrium phase (EP-NIC) were independent influencing factors. The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824, respectively, which were slightly greater than those of CT-T and CT-EMVI (AUC = 0.793, 0.762). The nomogram combining CT-T stage, CT-EMVI, VP-70 keV and EP-NIC yielded AUCs of 0.918 (0.866-0.954) and 0.874 (0.784-0.936) in the training and validation cohorts, which are significantly higher than using each of single independent factors (P < 0.05). CONCLUSION: The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC, with accuracy boosted by integrating clinical markers.

Simulation training of laparoscopic biliary-enteric anastomosis with a three-dimensional-printed model leads to better skill transfer: a randomized controlled trial.

AIM: A new simulation model and training curriculum for laparoscopic bilioenteric anastomosis has been developed. Currently, this concept lacks evidence for the transfer of skills from simulation to clinical settings. This study was conducted to determine whether training with a three-dimensional (3D) bilioenteric anastomosis model result in greater transfer of skills than traditional training methods involving video observation and a general suture model. METHODS: Fifteen general surgeons with no prior experience in laparoscopic biliary-enteric anastomosis were included in this study and randomised into three training groups: video observation only, practice using a general suture model, and practice using a 3D-printed biliary-enteric anastomosis model. Following five training sessions, each surgeon was asked to perform a laparoscopic biliary-enteric anastomosis procedure on an isolated swine organ model. The operative time and performance scores of the procedure were recorded and compared among the three training groups. RESULTS: The operation time in the 3D-printed model group was significantly shorter than the suture and video observation groups ( P =0.040). Furthermore, the performance score of the 3D-printed model group was significantly higher than those of the suture and video observation groups ( P =0.001). Finally, the goal score for laparoscopic biliary-enteric anastomosis in the isolated swine organ model was significantly higher in the 3D model group than in the suture and video observation groups ( P =0.004). CONCLUSIONS: The utilisation of a novel 3D-printed model for simulation training in laparoscopic biliary-enteric anastomosis facilitates improved skill acquisition and transferability to an animal setting compared with traditional training techniques.

LncRNA LUESCC promotes esophageal squamous cell carcinoma by targeting the miR-6785-5p/NRSN2 axis.

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent gastrointestinal malignancies with high mortality worldwide. Emerging evidence indicates that long noncoding RNAs (lncRNAs) are involved in human cancers, including ESCC. However, the detailed mechanisms of lncRNAs in the regulation of ESCC progression remain incompletely understood. LUESCC was upregulated in ESCC tissues compared with adjacent normal tissues, which was associated with gender, deep invasion, lymph node metastasis, and poor prognosis of ESCC patients. LUESCC was mainly localized in the cytoplasm of ESCC cells. Knockdown of LUESCC inhibited cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth in vivo. Mechanistic investigation indicated that LUESCC functions as a ceRNA by sponging miR-6785-5p to enhance NRSN2 expression, which is critical for the malignant behaviors of ESCC. Furthermore, ASO targeting LUESCC substantially suppressed ESCC both in vitro and in vivo. Collectively, these data demonstrate that LUESCC may exerts its oncogenic role by sponging miR-6785-5p to promote NRSN2 expression in ESCC, providing a potential diagnostic marker and therapeutic target for ESCC patients.

A Selective-Tumor-Penetrating Strategy via Unidirectional Direct Transfer for Intravesical Therapy of Bladder Cancer.

A selective tumor-penetrating strategy generally exploits tumor-targeted ligands to modify drugs so that the conjugate preferentially enters tumors and subsequently undergoes transcellular transport to penetrate tumors. However, this process shields ligands from their corresponding targets on the cell surface, possibly inducing an off-target effect during drug penetration at the tumor-normal interface. Herein, we first describe a selective tumor-penetrating drug (R11-phalloidin conjugates) for intravesical therapy of bladder cancer. The intravesical conjugates rapidly translocated across the mucus layer, specifically bound to tumors, and infiltrated throughout the tumor via direct intercellular transfer. Notably, direct transfer from normal cells to tumor cells was unidirectional because the pathways required for direct transfer, termed F-actin-rich tunneling nanotubes, were more unidirectionally extended from normal cells to tumor cells. Moreover, the intravesical conjugates displayed strong anticancer activity and well-tolerated biosafety in murine orthotopic bladder tumor models. Our study demonstrated the potential of a selective tumor-penetrating conjugate for effective intravesical anticancer therapy.

CircHIPK3 regulates fatty acid metabolism through miR-637/FASN axis to promote esophageal squamous cell carcinoma.

The oncogenic role of circRNA in cancers including esophageal cancer (EC) has been well studied. However, whether and how circRNAs are involved in cancer cell metabolic processes remains largely unknown. Here, we reported that circRNA, circHIPK3, is highly expressed in ESCC cell lines and tissues. Knockdown of circHIPK3 significantly restrained cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, circHIPK3 was found to act as a ceRNA by sponging miR-637 to regulate FASN expression and fatty acid metabolism in ESCC cells. Anti-sense oligonucleotide (ASO) targeting circHIPK3 substantially inhibited ESCC both in vitro and in vivo. Therefore, these results uncover a modulatory axis constituting of circHIPK3/miR-637/FASN may be a potential biomarker and therapeutic target for ESCC in the clinic.

Codelivery of Gaseous Signaling Molecules for Biomedical Applications.

Gaseous signaling molecules (GSMs) including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) have presented excellent therapeutic efficacy such as anti-inflammatory, anti-microbial and anti-cancer effects and multiple biomedical applications in recent years. As the three most vital signaling molecules in human physiology, these three GSMs show so intertwined and orchestrated interactions that the synergy of multiple gases may demonstrate a more complex therapeutic potential than single gas delivery. Consequently, researchers have been devoted to developing codelivery systems of GSMs by synthesizing a single molecule as a dual donor to maximize the gaseous therapeutic efficacy. In this minireview, we summarize the recent developments of molecules or materials enabling codelivery of GSMs for biomedical applications. It appears that compared with the abundant cases of codelivery of NO and H2S, research on codelivery of CO and the other two GSMs separately remains to be explored.

Treatment patterns and clinical outcomes of patients with resectable non-small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World).

BACKGROUND: Neoadjuvant immunotherapy has ushered in a new era of perioperative treatment for resectable non-small cell lung cancer (NSCLC). However, large-scale data for verifying the efficacy and optimizing the therapeutic strategies of neoadjuvant immunochemotherapy in routine clinical practice are scarce. METHODS: NeoR-World (NCT05974007) was a multicenter, retrospective cohort study involving patients who received neoadjuvant immunotherapy plus chemotherapy or chemotherapy alone in routine clinical practice from 11 medical centers in China between January 2010 and March 2022. Propensity score matching was performed to address indication bias. RESULTS: A total of 408 patients receiving neoadjuvant immunochemotherapy and 684 patients receiving neoadjuvant chemotherapy were included. The pathologic complete response (pCR) and major pathologic response (MPR) rates of the real-world neoadjuvant immunochemotherapy cohort were 32.8% and 58.1%, respectively. Notably, patients with squamous cell carcinoma exhibited significantly higher pCR and MPR rates than those with adenocarcinoma (pCR, 39.2% vs 16.5% [P < .001]; MPR, 66.6% vs 36.5% [P < .001]), whereas pCR and MPR rates were comparable among patients receiving different neoadjuvant cycles. In addition, the 2-year rates of disease-free survival (DFS) and overall survival (OS) rate were 82.0% and 93.1%, respectively. Multivariate analyses identified adjuvant therapy as an independent prognostic factor for DFS (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.89; P = .018) and OS (HR, 0.28; 95% CI, 0.13-0.58; P < .001). A significantly longer DFS with adjuvant therapy was observed in patients with non-pCR or 2 neoadjuvant cycles. We observed significant benefits in pCR rate (32.4% vs 6.4%; P < .001), DFS (HR, 0.50; 95% CI, 0.38-0.68; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.94; P = .024) with immunotherapy plus chemotherapy compared to chemotherapy alone both in the primary propensity-matched cohort and across most key subgroups. CONCLUSIONS: The study validates the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy alone for NSCLC. Adjuvant therapy could prolong DFS in patients receiving neoadjuvant immunochemotherapy, and patients with non-pCR or those who underwent 2 neoadjuvant cycles were identified as potential beneficiaries of adjuvant therapy.

Camrelizumab in combination with chemotherapy versus concurrent chemoradiotherapy for the conversion of locally advanced unresectable oesophageal squamous carcinoma: protocol for a two-arm, open-label phase II trial.

INTRODUCTION: Oesophageal cancer (OC) has higher morbidity and mortality rate than most other malignancies. The standard treatment for unresectable locally advanced oesophageal squamous cell carcinoma (OSCC) is concurrent chemoradiotherapy, with tumour regression observed in a proportion of patients after treatment, but prognostic improvement remains limited. Immunotherapy in combination with chemotherapy (CT) has been shown to be efficacious as the first-line treatment of advanced OC and neoadjuvant therapy. Therefore, we conducted a prospective, two-arm, randomised, unblinded phase II study to explore the efficacy of camrelizumab in combination with CT versus chemoradiotherapy for the conversion of unresectable advanced OSCC. METHODS AND ANALYSIS: All participants meeting the inclusion criteria will be enrolled after signing an informed consent form. Patients with clinically cT4b or spread to at least one group of lymph nodes with possible invasion of surrounding organs and unresectable locally advanced squamous carcinoma of the thoracic segment of the oesophagus will be included in the study. Patients with suspected distant metastases on the preoperative examination will be excluded from this study. Patients eligible for enrolment will be grouped by centre randomisation according to the study plan. Patients will undergo radical surgery after completion of two cycles of chemotherapy (CT) combined with camrelizumab induction therapy or concurrent chemoradiotherapy if assessed to be operable. Patients evaluated as inoperable will be scheduled for a multidisciplinary consultation to determine the next treatment option. The primary endpoint is the R0 resection rate in patients undergoing surgery after treatment. Secondary endpoints are the rate of major pathological remission, pathological complete response rate, overall survival, progression-free survival and adverse events for all patients. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethics committees of Fujian Medical University Union Hospital (No. 2022YF039-02). The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05821452.

Incorporation of Decidual Stromal Cells Derived Exosomes in Sodium Alginate Hydrogel as an Innovative Therapeutic Strategy for Advancing Endometrial Regeneration and Reinstating Fertility.

Intrauterine adhesion (IUA) stands as a prevalent medical condition characterized by endometrial fibrosis and scar tissue formation within the uterine cavity, resulting in infertility and, in severe cases, recurrent miscarriages. Cell therapy, especially with stem cells, offers an alternative to surgery, but concerns about uncontrolled differentiation and tumorigenicity limit its use. Exosomes, more stable and immunogenicity-reduced than parent cells, have emerged as a promising avenue for IUA treatment. In this study, a novel approach has been proposed wherein exosomes originating from decidual stromal cells (DSCs) are encapsulated within sodium alginate hydrogel (SAH) scaffolds to repair endometrial damage and restore fertility in a mouse IUA model. Current results demonstrate that in situ injection of DSC-derived exosomes (DSC-exos)/SAH into the uterine cavity has the capability to induce uterine angiogenesis, initiate mesenchymal-to-epithelial transformation (MET), facilitate collagen fiber remodeling and dissolution, promote endometrial regeneration, enhance endometrial receptivity, and contribute to the recovery of fertility. RNA sequencing and advanced bioinformatics analysis reveal miRNA enrichment in exosomes, potentially supporting endometrial repair. This finding elucidates how DSC-exos/SAH mechanistically fosters collagen ablation, endometrium regeneration, and fertility recovery, holding the potential to introduce a novel IUA treatment and offering invaluable insights into the realm of regenerative medicine.

The Antioxidant Mechanism of Peptides Extracted from Tuna Protein Revealed Using a Molecular Docking Simulation.

Tuna protein serves as a significant source of bioactive peptides, and its functional properties can be elucidated through predictive modeling, followed by experimental validation. In this study, the active polypeptides were obtained from tuna protein via enzymatic hydrolysis (TPP), and their peptide sequences were determined. Furthermore, the potential activity of these peptides was predicted, focusing on antioxidant peptides, and compared to the sequence library of known antioxidant peptides to identify common structural motifs. The accuracy of the prediction results was confirmed through in vitro antioxidant assays and molecular docking studies. We identified seven specific peptide segments derived from tuna protein that exhibit antioxidant potential, accounting for approximately 15% of all active peptides. Molecular docking and cell experiments were employed to provide compelling evidence for the presence of antioxidant peptides within tuna protein. This study not only lays a solid foundation for studying the structure of active peptides but also opens up a novel avenue for an expedited assessment of their properties.