INTRODUCTION:This study aimed to investigate the potential relationship between live microbe intake and advanced liver fibrosis in patients with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD). METHODS:Individuals with complete Vibration-Controlled Transient Elastography (VCTE) and dietary data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were included. Generalized Additive Models (GAMs) were constructed to evaluate the relationship between live microbe intake and severity of hepatic steatosis and fibrosis, adjusting for potential confounders. Subgroup analyses and interaction tests assessed potential modifying effects of sex, age, Body Mass Index (BMI), liver enzymes, and alcohol consumption. Sensitivity analyses were performed to confirm robustness. RESULTS:A total of 2,533 individuals with MASLD were analyzed. GAM analyses showed no significant association between dietary live microbe intake and hepatic steatosis severity measured by Controlled Attenuation Parameter (CAP) (p = 0.779). However, there was a significant inverse relationship between live microbe intake and Liver Stiffness Measurement (LSM), indicating reduced liver fibrosis severity with higher microbe intake (p = 0.004). Subgroup and interaction analyses consistently supported this association across different age groups, sexes, BMI categories, and liver enzyme levels. DISCUSSION:These findings highlight a significant association between higher dietary intake of live microbes and reduced severity of liver fibrosis, emphasizing the potential role of dietary modification in managing liver fibrosis in MASLD. CONCLUSION:Higher dietary intake of live microbes is significantly associated with reduced liver fibrosis severity in MASLD, suggesting a potential protective role of dietary microbes in liver health.

Endometriosis is a chronic inflammatory disease characterized by the ectopic growth of endometrial-like tissue and is closely associated with pain and infertility. This review summarizes current evidence on immune dysregulation and emerging immunomodulatory therapies in endometriosis. Relevant clinical and mechanistic studies were identified through a structured literature review and qualitatively synthesized. Increasing evidence suggests that immune dysregulation plays a critical role in disease pathogenesis. Within the immune microenvironment, innate and adaptive immune cells—including macrophages, dendritic cells, neutrophils, mast cells, T cells, and B cells—collectively promote inflammation, angiogenesis, fibrosis, and immune evasion. Emerging immunotherapeutic strategies, including macrophage repolarization, NK cell restoration, dendritic cell modulation, neutrophil extracellular traps inhibition, immune checkpoint blockade, and cytokine/chemokine targeting, have shown promising preclinical and early clinical potential. However, disease heterogeneity, reproductive safety concerns, and the lack of validated biomarkers remain major barriers to clinical translation, highlighting the potential of immunomodulatory therapies as future non-hormonal treatment strategies.

Old World orthohantaviruses, including Hantaan virus (HTNV), cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Available inactivated vaccines often induce low neutralizing antibodies and short-term protection. We evaluated nucleic acid vaccines expressing a prefusion-stabilized HTNV glycoprotein in female BALB/c mice. Both DNA and mRNA-LNP versions elicited robust neutralizing antibodies by strongly activating germinal centers, which protected mice against high-dose HTNV challenge. We further tested heterologous prime-boost regimens, where mice primed with inactivated vaccine received different boosters. All boosters increased neutralizing titers, but only the prefusion-stabilized glycoprotein mRNA-LNP vaccine raised titers to the level achieved by its own full primary vaccination course. This demonstrates the immunogen's superiority in developing next-generation vaccines and its unique ability to potently recall memory B cells induced by suboptimal inactivated vaccines. Thus, prefusion-stabilized glycoprotein-based nucleic acid vaccines are promising candidates for advanced orthohantavirus vaccine development.

Objective To prepare mouse-derived specific monoclonal antibody against human adenovirus type 55 fiber protein (HAdV55 Fiber). Methods Gene synthesis technology was used to successfully construct the prokaryotic expression vector pET28a-HAdV55 Fiber and the eukaryotic expression vector pCAGGS-HAdV55 Fiber. After transformation of the recombinant plasmid pET28a-HAdV55 Fiber into competent cells BL21(DE3), the target protein was purified using the AKTA pure system after IPTG induction. BALB/c mice were first immunized with pCAGGS-HAdV55 Fiber plasmid by the cupping method, with three basic immunizations at intervals of 21 days; followed by two booster immunizations with purified Fiber protein via the intraperitoneal injection. Three days post-final immunization, splenocytes from mice with high antibody titer were fused to SP2/0 myeloma cells, and hybridomas were screened via limiting dilution to yield mAbs targeting Fiber protein, whose subtypes and ascites titers were subsequently characterized. The immunofluorescence method was used to detect the reactivity of the monoclonal antibodies against Fiber protein expressed in BHK-21 cells transfected with pCAGGS-HAdV55 Fiber. To identify antibody pairs capable of effectively detecting HAdV55, we employed the anti-HAdV55 Hexon monoclonal antibody previously generated by our group as the capture antibody and the aforementioned HRP-labeled Fiber antibody as the detection antibody. Results The pET28a-HAdV55 Fiber and pCAGGS-HAdV55 Fiber expression plasmids were successfully constructed; the Fiber protein was inducibly expressed via IPTG from BL21 (DE3) E. coli cells transformed with the pET28a-HAdV55 Fiber plasmid. Five hybridoma cells are successfully obtained, which can continuously secrete anti-fibritin monoclonal antibodies. Among them, 2A4F3 could recognize the Fiber protein expressed in eukaryotic cells. From a panel of candidate antibodies, an optimal antibody pair with anti-Hexon mAb 2D3 (capture) and anti-Fiber mAb 2A4F3 (detection) was identified for sensitive detection of HAdV55 via double-antibody sandwich ELISA. Conclusion In this study, specific antibodies against the HAdV55 Fiber protein were successfully prepared, and a specific detection method for HAdV55 was initially established.

Background Gastric cancer (GC) remains a major global health burden, and minimally invasive approaches have become a primary focus in surgical oncology. Natural orifice specimen extraction surgery (NOSES) for GC integrates laparoscopic radical gastrectomy with specimen retrieval via natural orifices, aiming to minimize abdominal wall trauma while ensuring oncologic safety. Methods This guideline was developed through a comprehensive literature review, multidisciplinary expert panel discussions, and synthesis of accumulated clinical experience in GC-NOSES. The recommendations address operative platforms, aseptic and tumor-free techniques, digestive tract reconstruction, and procedure-specific steps. Emphasis was placed on perioperative safety, oncologic principles, and standardization of surgical procedures. Results Although most existing studies are small-scale, single-center, and retrospective, accumulating data suggest that GC-NOSES offers comparable oncological outcomes to conventional laparoscopic gastrectomy while reducing postoperative pain, accelerating gastrointestinal recovery, shortening hospital stay, and improving cosmetic satisfaction. Conclusion GC-NOSES is a promising minimally invasive option with potential benefits in postoperative recovery and quality of life. Standardized procedures, structured training, and high-quality multicenter studies are essential to further confirm its safety, refine indications, and promote global implementation.

The Astragalus membranaceus - Codonopsis pilosula decoction (ACD), is traditionally used as beverage to activate immunity. This study aimed to investigate the combined use of ACD and TP (paclitaxel and cisplatin) against non-small cell lung cancer (NSCLC) in a orthotopic mouse model. In this study, the anti-tumor and immunomodulation efficacies of ACD and TP were evaluated in an orthotopic lung cancer model. After treatment with ACD for one week, the luciferase-expressing Lewis cells were injected into the lungs of male C57 mice and treated with ACD and/or TP for about 2 weeks. Then, the flow cytometry, ELISA, IHC and WB were employed to assess immune cell populations, cytokine production and protein expression levels. Besides, in vitro cytotoxicity of ACD against NSCLC cells was performed using CCK-8 assays, while its immunomodulatory potential was evaluated using a co-culture system incorporating NSCLC cells and patient-derived PBMCs. Our results demonstrated that combination of ACD and TP had the most potent effects on tumor burden and immunity activation among treatment groups. ACD (1 g/kg) and TP (paclitaxel 22.5 mg/kg, cisplatin 12.5 mg/kg) treatment reduced tumor burden by 53.16%, as validated by IVIS imaging in the mouse model. Flow cytometry from mice spleens proved that the combined use of ACD and TP treatment significantly decreased Treg production and increased CD4+ and CD8+ T cell infiltration. Besides, ACD and TP treatment resulted in downregulation of FOXP3 and EZH2 expression, and suppression of PI3K/AKT phosphorylation in mice tumor. Furthermore, in vivo results showed that ACD had no direct cytotoxicity against NSCLC cells, which significantly enhanced PBMC-mediated tumor cell killing and promoted IFN-γ and TNF-α production in patient-derived co-culture systems. In conclusion, the combination of ACD plus TP demonstrated potent anti-tumor and immunomodulation effects against NSCLC in association with reduced Treg activity and increased CD8+ T cell infiltration. Our study provides compelling preclinical evidence supporting ACD as an immunomodulatory adjunct to conventional NSCLC therapies.

Subsequently to the publication of the above paper, a concerned reader has drawn to the Editor's attention that, for the western blot data shown in Fig. 2A and B on p. 71, certain of the protein bands looked strikingly similar to others, where the results of differently performed experiments were intended to have been represented (considering both the forward orientations of the bands in question, and occasionally, bands positioned in the reverse orientation). The Editorial Office has investigated this matter independently, and reached the same concluson as the reader that certain of the data appeared to have been duplicated within Fig. 2A and B. Given that this issue has come to light, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 34: 67‑76, 2015; DOI: 10.3892/or.2015.3999].

Background: Tumor-associated macrophages (TAMs) are pivotal mediators of the immunosuppressive tumor immune microenvironment (TIME) in colorectal cancer (CRC). However, genes of TAMs that potentiate immunotherapy remain to be explored. Methods: Single-cell RNA sequencing (scRNA-seq) data were analyzed to identify TAM molecular signatures, which were validated in patient cohorts from Huadong Hospital and TCGA to explore their clinical significance. Multidimensional characterization of CRC TIME and Dipeptidyl peptidase VII (DPP7)-positive TAMs functional state was achieved through cytometry by time-of-flight, multiplex immunofluorescence, in vitro and in vivo experiments. Mechanistic investigations integrating RNA-seq, Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-based proteomics, and targeted lipid metabolomics have revealed the reprogramming of key metabolic pathways. Finally, the therapeutic potential of DPP7, which targets the enhancement of anti-PD-1 immunotherapy efficacy, was demonstrated. Results: DPP7 was identified as the key gene in TAMs, and DPP7+TAMs correlated with metastasis and worse overall survival in multiple clinical cohorts. Functional characterization demonstrated that DPP7+TAMs drove the immunosuppressive TIME and promoted the exhaustion of CD8+T cells, thus exhibiting M2-polarized features. Mechanistically, DPP7 reduced ubiquitination-induced degradation of Carnitine Palmitoyltransferase 1A (CPT1A) by binding to CPT1A in a mutually exclusive manner with TRIM25, thus enhancing fatty acid oxidation (FAO) in TAMs. This metabolic reprogramming consumes lipids (including triglycerides and free fatty acids), elevates adenosine triphosphate (ATP) generation, and induces an immunosuppressive phenotype. In vivo, DPP7 knockdown in bone marrow-derived macrophages (BMDMs) synergized with anti-PD-1 therapy, achieving significant suppression of subcutaneous xenograft tumor growth and liver metastatic burden by reversing the immunosuppressive TIME. Conclusions: DPP7 is mainly expressed in TAMs and DPP7+TAMs are strongly associated with adverse prognosis in CRC. Mechanistically, DPP7 enhances FAO to promote the M2-polarized phenotype in TAMs, leading to an immunosuppressive TIME. Targeting DPP7+TAMs may potentiate the efficacy of immunotherapy for CRC.

Robotic surgery for rectal cancer is widely used, but data on long-term oncological outcomes are still lacking. To compare the 3-year locoregional recurrence rates of middle and low rectal cancer in patients who underwent robotic surgery vs conventional laparoscopic surgery. In this multicenter, superiority, randomized clinical trial, patients with middle or low rectal adenocarcinoma (cT1-T3, N0-N1, or ycT1-T3 Nx) and no distant metastasis were enrolled at 11 centers across 8 provinces in China from July 2016 to December 2020. Among the 1742 consecutive patients assessed for eligibility, 1240 were eligible and randomized. Follow-up continued until December 31, 2023. Patients were randomized 1:1 to undergo robotic or conventional laparoscopic rectal cancer resection. The primary outcome was the 3-year locoregional recurrence rate. The primary analysis was performed as randomized, but excluded patients deemed ineligible after randomization. The secondary outcomes included disease-free survival; overall survival; and urinary, sexual, and defecation function. Of the 1240 patients enrolled, 1171 were included in the primary analysis (586 in the robotic surgery group; mean age, 59.1 [SD, 11.0] years; and 356 were men [60.8%] vs 585 in the laparoscopic surgery group; mean age, 60.7 [SD, 9.8] years; and 354 were men [60.5%]). The median follow-up time was 43.0 months (IQR, 36.7-60.0 months). The 3-year locoregional recurrence rate was 1.6% (95% CI, 0.6%-2.6%) in the robotic group vs 4.0% (95% CI, 2.4%-5.6%) in the laparoscopic group (hazard ratio [HR], 0.45 [95% CI, 0.22-0.92], log-rank P = .03; adjusted HR, 0.39 [95% CI, 0.19-0.80]). The 3-year disease-free survival rate was higher in the robotic group (87.2%) vs the laparoscopic group (83.4%) (HR, 0.74 [95% CI, 0.56-0.98], log-rank P = .04; adjusted HR, 0.67 [95% CI, 0.50-0.89]). No significant between-group difference was observed in 3-year overall survival (94.7% in the robotic group vs 93.0% in the laparoscopic group). Patients in the robotic group also had better urinary function, male and female sexual function, and defecation function at 3 and 6 months after surgery and better urinary function and male sexual function at 12 months after surgery. Compared with conventional laparoscopic surgery, robotic surgery significantly improved long-term oncological outcomes in patients with middle or low rectal cancer. With additional real-world clinical data and modern, improved training programs for surgeons, robotic surgery could be the preferred choice for patients with middle or low rectal cancer. ClinicalTrials.gov Identifier: NCT02817126.

BackgroundMalignant peritoneal mesothelioma (MPM) is an exceptionally rare tumor type, and its molecular properties are poorly understood. In recent years, gene rearrangement has been found in a subset of MPMs. However, ROS1 rearrangement has not been previously reported in MPM.Case presentationHere, we present the first case report of MPM with TFG-ROS1 rearrangement in a 56-year-old female with no history of asbestos exposure. The patient did not respond to immunotherapy but exhibited sensitivity to crizotinib with a progression-free survival (PFS) of 6 months. Importantly, we identified ROS1 p.K1991N as a potential acquired drug resistance mutation to crizotinib, suggesting that entrectinib may serve as a targeted therapy to overcome this resistance mechanism.ConclusionROS1 rearrangement could potentially represent a novel driver mutation in MPM, especially in female adults. This case report illustrates the benefits of molecular detection in MPM and underscores the potential for lessons learned from other solid tumors to inform treatment strategies for rare diseases.

Background Colorectal cancer (CRC) is a highly immunosuppressive malignancy characterized by limited therapeutic options and a poor prognosis. Within the CRC tumor immune microenvironment (TIME), tumor-associated macrophages (TAMs) represent the predominant immune cell population. This study aimed to characterize the specific macrophage subsets contributing to CRC progression and resistance to immunotherapy. Methods Single-cell RNA sequencing (scRNA-seq) was used to identify the key macrophage marker genes. The clinical significance of death-associated protein kinase 1 (DAPK1), was evaluated in clinical CRC cohorts using immunohistochemistry, immunofluorescence, Kaplan-Meier plots and Cox Proportional Hazards Models. Cytometry by time-of-flight, RNA-seq, flow cytometry and an in vitro co-culture system were performed to explore the functional role of macrophage-derived DAPK1 in the TIME. Subcutaneous tumor models and splenic-liver metastasis models were constructed to assess the potential of DAPK1 inhibition to enhance immune checkpoint blockade (ICB) efficacy. Results scRNA-seq analysis revealed predominant DAPK1 expression in intratumoral macrophages of CRC TIME. Elevated macrophage-specific DAPK1 level was significantly associated with worse prognosis. DAPK1(+)TAMs exhibited immunosuppressive properties and inhibit CD8(+)T cells cytotoxicity. Pharmacological inhibition of DAPK1 enhanced the efficacy of anti-PD-1 therapy in murine models. Conclusions DAPK1(+)TAMs infiltration was an independent risk factor for overall survival in patients with CRC. These DAPK1(+)TAMs exhibit an immunosuppressive phenotype and promote the establishment of the TIME with immune evasion. Targeting DAPK1 may represent a potential strategy for synergizing immunotherapy in CRC treatment.

Importance Robotic surgery for rectal cancer is widely used, but data on long-term oncological outcomes are still lacking. Objective To compare the 3-year locoregional recurrence rates of middle and low rectal cancer in patients who underwent robotic surgery vs conventional laparoscopic surgery. Design, Setting, and Participants In this multicenter, superiority, randomized clinical trial, patients with middle or low rectal adenocarcinoma (cT1-T3, N0-N1, or ycT1-T3 Nx) and no distant metastasis were enrolled at 11 centers across 8 provinces in China from July 2016 to December 2020. Among the 1742 consecutive patients assessed for eligibility, 1240 were eligible and randomized. Follow-up continued until December 31, 2023. Interventions Patients were randomized 1:1 to undergo robotic or conventional laparoscopic rectal cancer resection. Main Outcomes and Measures The primary outcome was the 3-year locoregional recurrence rate. The primary analysis was performed as randomized, but excluded patients deemed ineligible after randomization. The secondary outcomes included disease-free survival; overall survival; and urinary, sexual, and defecation function. ResultsOf the 1240 patients enrolled, 1171 were included in the primary analysis (586 in the robotic surgery group; mean age, 59.1 [SD, 11.0] years; and 356 were men [60.8%] vs 585 in the laparoscopic surgery group; mean age, 60.7 [SD, 9.8] years; and 354 were men [60.5%]). The median follow-up time was 43.0 months (IQR, 36.7-60.0 months). The 3-year locoregional recurrence rate was 1.6% (95% CI, 0.6%-2.6%) in the robotic group vs 4.0% (95% CI, 2.4%-5.6%) in the laparoscopic group (hazard ratio [HR], 0.45 [95% CI, 0.22-0.92], log-rank P = .03; adjusted HR, 0.39 [95% CI, 0.19-0.80]). The 3-year disease-free survival rate was higher in the robotic group (87.2%) vs the laparoscopic group (83.4%) (HR, 0.74 [95% CI, 0.56-0.98], log-rank P = .04; adjusted HR, 0.67 [95% CI, 0.50-0.89]). No significant between-group difference was observed in 3-year overall survival (94.7% in the robotic group vs 93.0% in the laparoscopic group). Patients in the robotic group also had better urinary function, male and female sexual function, and defecation function at 3 and 6 months after surgery and better urinary function and male sexual function at 12 months after surgery. Conclusions and Relevance Compared with conventional laparoscopic surgery, robotic surgery significantly improved long-term oncological outcomes in patients with middle or low rectal cancer. With additional real-world clinical data and modern, improved training programs for surgeons, robotic surgery could be the preferred choice for patients with middle or low rectal cancer.

Hantaan virus (HTNV), a major etiologic agent of hemorrhagic fever with renal syndrome (HFRS), poses a significant threat to global public health. Currently, there are no clinically approved antiviral drugs specifically for HTNV infection, nor are there any highly effective preventive vaccines. Thus, the development of effective therapeutic strategies is critically important. This study investigated the antiviral efficacy of morin against HTNV and its potential mechanism of action using in vitro assays. Our results demonstrate that morin inhibits HTNV infection in a concentration-dependent manner and primarily targets the post-entry replication stage of the viral life cycle. Further mechanistic studies revealed that morin exerts its antiviral effects by directly interacting with the HTNV nucleocapsid protein (NP). In conclusion, this study identifies morin as a promising candidate for anti-HTNV drug development, providing a new strategic direction for HFRS treatment.

177 Background: Surgery is standard of care for pMMR early distal rectal cancer (RC), which can be partially exempted by totally neoadjuvant chemoradiotherapy (TNT) followed by watch and wait. But long-term data showed that 1/3 patients had local growth( mostly in the rectal wall)in two years. This study investigates the efficacy and safety of TNT followed by local excision( LE) for early distal rectal carcinoma (cT1-3N0M0) in order to preserve organs. Methods: In this single-arm, phase 2 prospective trial, patients were eligible if they were aged 18 years or older, with a performance status of 0-1,newly diagnosed, biopsy proven pMMR/MSS RC which located ≤5cm from the anal verge and staged as cT1-3N0M0. Patients were assigned to receive TNT: 6 courses of CapOx(capecitabine 1000 g/m2 PO BID D1-14, oxaliplatin 130 mg/m2 IV QD D1,Q3W), combined with concurrent long-course radiotherapy (LCRT)(45 Gy/25 Fx to the pelvis with an SIB of 50 Gy/25 Fx to the tumor bed). Evaluation was performed 12 weeks after completion of LCRT. Patients who achieved a clinical complete response (cCR) or near clinical complete response (ncCR)were assigned to LE, whereas those with >ypT1, positive margin, or neurovascular invasion after LE were recommended for total mesorectal excision (TME). The primary endpoint is the 3-year organ-preserving rate. Secondary endpoints include the pathological complete response (pCR)(encompassing response after LE and TME), adverse effects rate, 3y-disease-free survival (DFS)and 3y-overall survival (OS)rate. Results: From October 2022 to August 2024, 52 patients had completed therapy. Median age at evaluation and follow-up duration were 58.3 years and 11 months. Of the patients 78.8% (41/52) were defined as MRI stage T3, and 76.9%(40/52) located ≤3cm from the anal verge. Of 52 evaluable patients ,82.7% (43/52) achieved cCR/ncCR and had LE (6 via endoscopic resection and 37 through trans-anal minimally invasive surgery). Among these patients, 25.6% (11/43) were found to have residual tumors after LE, of which 6 were radical-operated while 5 refused this intervention. Nine patients who did not achieve cCR or ncCR received TME resection, and 6 of them were confirmed as pCR. The total pCR rate was 73.1% (38/52). Of all patients, 3 underwent abdominoperineal resection, and sphincter-preserving rate was 94.2%(49/52). No grade 3 or 4 adverse events were reported, and there were no treatment-related deaths. The main adverse event after local resection was the 1-3 months anterior resection syndrome. Conclusions: The results of interim analysis showed that tumor residue was found in patients with cCR/ncCR after TNT, similar to the regrowth rate previously reported. LE strategy may become prevention. Long-term outcomes are being followed up. Clinical trial information: NCT05563922 .

TPS315 Background: CRT followed by total mesorectal excision (TME) is the standard care for patients with locally advanced low rectal cancer (≤ 5cm from the anal margin). However, TME may lead to permanent colostomy and severely impact quality of life. Organ preservation is, therefore, a critical unmet need for these patients. The proportion of patients achieving clinical complete response (cCR) after CRT is relatively low, with the literature reporting around 20%. Total neoadjuvant therapy (TNT) has been investigated to increase cCR rate. Several clinical trials demonstrated that PD-1 inhibitor combined with TNT could result in significate improvement in pathological complete response rate (pCR rate, 39.8% vs 15.3%, p < 0.001 in UNION study) or complete response rate (pCR+cCR rate, 44.8% vs 26.9%, p = 0.031 in a randomized phase 2 study) compared with TNT alone in rectal cancer patients. The RELIEVE-01 study (NCT06390982) was designed to evaluate the efficacy in organ preservation with CRT followed by sequential TIS + CAPOX and TIS monotherapy in patients with low rectal cancer. Methods: This multicenter, single-arm, phase 2 study will enroll 46 pts with histopathologically confirmed rectal adenocarcinoma (≤ 5cm from the anal margin), pMMR/MSI-L/MSS, cT1-3N1M0/T2-3N0M0, and ECOG PS ≤1. Pts will initially receive 6 weeks of CRT (50.4 Gy/28F, capecitabine 825 mg/m 2 , bid, d1-5 each week), followed by 4 cycles of TIS + CAPOX (TIS, 200 mg, IV, d1; capecitabine 1000 mg/m 2 , bid, d1-14; oxaliplatin 130 mg/m 2 , d1) in a 21-day cycle. Then, clinical response will be assessed to determine the subsequent treatment. Patients with cCR will receive TIS + CAPOX (4 cycles) and TIS (up to 9 cycles), and then be managed using the W&W strategy. Patients with non-cCR will undergo TME. Patients with near-cCR will be given local excision, and those achieving pCR will receive the same treatment as cCR patients, and for those with non-pCR after local excision, TME will be performed. The primary endpoint is rate of CR (cCR plus pCR post local resection). Secondary endpoints include organ-preserving rate, event-free survival rate and OS rate at 1, 2 and 3 years, respectively. Recruitment is ongoing. Clinical trial information: NCT06390982 .

Background:There is no consensus on the adjuvant treatment regimen for patients with colorectal cancer liver metastasis (CRLM) who have achieved successful conversion after surgery. This study aimed to compare the efficacy and safety of chemotherapy alone (CA) versus chemotherapy plus targeted therapy (CT) as adjuvant therapy for CRLM patients. Methods:Initially unresectable CRLM patients who were converted to hepatectomy with no evidence of disease between June 2013 and June 2020 were retrospectively analysed. The baseline characteristics were balanced between the CA and CT cohorts by using 1:2 propensity score matching (PSM). After PSM, disease-free survival (DFS) and overall survival (OS) were evaluated. A comprehensive subgroup analysis compared the efficacy between the cohorts, with DFS and OS assessed by using a stratified log-rank test and summarized by using Kaplan-Meier and Cox proportional hazards methods. Results:After PSM, 66 CA and 132 CT patients were included. DFS and OS were similar between the CA and CT cohorts (median DFS: 8.5 vs 10.8 months; median OS: 51.7 vs 56.5 months; both P > 0.050). In the CT cohort, subgroup analysis indicated a favorable trend of DFS for patients with KRAS/NRAS/BRAF mutations and receiving up to four cycles of conversion therapy (P_interaction, 0.005 and 0.013, respectively). In the KRAS/NRAS/BRAF-mutated cohort, CT significantly improved median DFS compared with CA (11.3 vs 7.4 months; hazard ratio, 0.42; 95% confidence interval, 0.26-0.69; P < 0.001). Conclusion:CT, as adjuvant therapy, effectively reduced intrahepatic and extrahepatic recurrence in initially unresectable CRLM patients. The patients with KRAS/NRAS/BRAF mutations or undergoing up to four cycles of conversion therapy benefited more from CT than from CA.

Rodent-borne orthohantavirus causes severe hemorrhagic fever worldwide, with hemorrhagic fever with renal syndrome (HFRS) in Eurasia, and hantavirus cardiopulmonary syndrome (HCPS) in the Amrerica. In East Asia, Hantaan orthohantavirus (HTNV) is the main pathogen responsible for severe HFRS, with a case fatality rate up to 10 % with no specific treatment available. The antisera or neutralizing antibody (NAb) is able to block virus infection, however, the traditional NAb titer measuring based on focus reduction neutralization test (FRNT) is quite labour-extensive and takes 7-10 days. This study aims to shorten the measuring time of NAb neutralization efficiency by 1-2 days based on quantitative RT-PCR. For this purpose, we developed an in vitro transcripted viral RNA standard and generated a viral RNA copy number standard curve. Using this standard curve, we compared the HTNV propagation kinetics between viral RNA copy numbers and secreted infectious virion. The detection limit and suitable timeframe and condition for qRT-PCR based viral RNA copy numbers measuring was also determined. In addition, when applying this method to measuring the NAb neutralization efficiency of HFRS convalescent serum samples, we could obtain the NAb neutralization efficiency within 1 or 2 days. Furthermore, this method was also nicely correlated with the FRNT - based NAb measurement. To conclude, we established a rapid and convenient viral RNA transcripts copy reduction neutralization test (VcRNT) to measure NAb neutralization efficiency that could finish within 1 or 2 days, and provided a reliable and efficient alternative for FRNT.

Background: Anastomotic leakage are common and serious complications after surgery for low and intermediate rectal cancers; a prophylactic stoma is thought to reduce the incidence of anastomotic leakage and alleviate its serious complications. However, it also comes with numerous risks. This study will investigate the value of prophylactic stomas in robot-assisted radical surgery for low and intermediate rectal cancers. Methods: We included 670 patients with low-to-intermediate rectal cancer who underwent robot-assisted radical resection at two hospitals within Fudan University from June 2016 to October 2022 (77 underwent prophylactic stoma and 593 did not have prophylactic stoma). The clinical data of the patients were collected and analyzed using a propensity score matching method that matched the groups at a 1:1 ratio based on sex, diabetes mellitus, body mass index, neoadjuvant chemoradiotherapy, distance of the lower edge of the tumor from the anal verge, maximum diameter of the tumor, and preoperative incomplete obstruction. Results: Patients in the prophylactic stoma group had a significantly lower incidence of symptomatic anastomotic leakage than the non-stoma group. There were no significant differences in the overall postoperative complication, unplanned readmission, or 30-day postoperative reoperation rates between the groups; however, the prophylactic stoma group had a lower number of postoperative hospital days and lower average hospital costs. Preoperative bowel obstruction was an independent risk factor for postoperative anastomotic leakage in the prophylactic stoma group. Conclusions: Prophylactic stomas based on a robotic platform are beneficial for some high-risk patients with low-to-intermediate rectal cancer.

Background: Dengue virus (DENV) infection, caused by serotypes DENV 1-4, represents a significant global public health challenge, with no antiviral drugs currently available for treatment. The host Protein kinase B (AKT) signaling pathway is crucial for DENV infection, presenting a potential target for antiviral drug development. Objective: This study aimed to evaluate the antiviral activity of kinase inhibitors that target the AKT pathway, focusing on the compound AT13148. Methods: A mini-screening was conducted to identify kinase inhibitors with antiviral properties against DENV-2. The effects of AT13148 on viral RNA replication and translation were assessed in a dose- and time-dependent manner following DENV-2 entry. The mechanism of action was further investigated by evaluating the impact of AT13148 on AKT kinase activity and phosphorylation status. Results: AT13148 exhibited potent antiviral activity against DENV-2, significantly inhibiting viral RNA replication and translation post-entry. The compound was found to inhibit AKT kinase activity through hyperphosphorylation. Conclusion: The findings indicate that AT13148 effectively targets the AKT pathway, demonstrating potential as an antiviral therapeutic against DENV-2 by interfering with the virus's post-entry processes. Further in vivo studies are warranted to assess the efficacy of AT13148 in controlling DENV infection.