The pattern of tumor progression on first-line immune checkpoint inhibitor-based systemic therapy for Chinese advanced hepatocellular carcinoma -CLEAP 004 study.

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.

Clinical significance of geriatric nutritional risk index in esophageal squamous cell carcinoma receiving neoadjuvant immunotherapy.

OBJECTIVE: The geriatric nutritional risk index (GNRI) is a novel nutrition-related indicator designed to predict the risk of clinical outcomes in various cancers. The clinical significance of risk assessment, therapeutic response, and prognostic prediction of GNRI in esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunochemotherapy (NICT), a hot point of treatment these days, have not been documented in any research. METHODS: Two hundred and twenty-four cases with ESCC who underwent radical resection after NICT were retrospectively recruited. Using the calculation formula of GNRI (1.489 × albumin (g/L) + 41.7 × current weight/ideal weight), the cases were split into two cohorts. Analysis was done on the connections between GNRI and clinical outcomes, such as clinical features, postoperative complications, and pathological complete response (pCR). Prognostic factors of overall survival (OS) and disease-free survival (DFS) were also performed. RESULTS: Patients were then categorized as low (n = 139) or high (n = 85) group based on the threshold. After radical surgery, 67 patients achieved pCR (29.9%). Higher pCR rates were attained by patients in the high GNRI group (41.2% vs. 23.0%, P = 0.004). Lower GNRI patients experienced a considerably higher severe morbidity (36.7% vs. 23.5%, P = 0.040), particularly in the case of respiratory complications (28.8% vs. 14.1%, P = 0.012). Compared to high GNRI patients, lower GNRI cases had inferior 3-year OS (68.5% vs. 87.3%, P = 0.003) and DFS (64.8% vs. 81.5%, P = 0.002). It was also discovered that GNRI was a significant independent variable of both DFS [hazard ratios (HR) = 0.436, P = 0.009] and OS (HR = 0.294, P = 0.012). CONCLUSION: The GNRI, based on nutrition-related indicators, was independently related to postoperative complications, pCR prediction, and prognostication in ESCC receiving NICT.

Change of indocyanine green clearance ability and liver function after transcatheter intra-arterial therapies and its impact on outcomes of resectable hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: Indocyanine green (ICG) clearance test is a classical measurement of hepatic reserve, which involves surgical safety and patient recovery of hepatocellular carcinoma (HCC). The authors aim to compare effects of hepatic arterial infusion chemotherapy (HAIC) and transcatheter arterial chemoembolization (TACE) on liver function and outcomes of subsequent hepatectomy. MATERIAL AND METHODS: HCC patients receiving HAIC/TACE in SYSUCC with repeated ICG clearance tests were retrospectively enrolled. ICG eliminating rate (ICG-K), ICG retention rate at 15 min (ICG-R15) and ordinary laboratory tests were collected. Peri-therapeutic changes of values were compared between the groups. Propensity score matching (PSM) and inverse probability of treatment weighing (IPTW) were employed to validate findings. Post-hepatectomy liver failure (PHLF), overall survival (OS) and recurrence-free survival (RFS) were analyzed in patients with subsequent curative hepatectomy. RESULTS: Two hundred and four patients treated with HAIC ( n =130) and TACE ( n =74) were included. ΔICG-R15 was greater in the HAIC arm before matching (mean, 3.8% vs. 0.7%, P <0.001), after PSM (mean, 4.7% vs. 1.1%, P =0.014) and IPTW (mean, 2.0% vs. -3.6%, P <0.001). No difference was found for ΔALB, ΔALBI, ΔTBIL, ΔALT, ΔAST and ΔPT-INR. Multivariable analyses revealed elder age, cirrhosis, HAIC, greater ΔTBIL and ΔALBI were associated with deteriorating ICG-R15. Among those (105 for HAIC and 48 for TACE) receiving hepatectomy, occurrence of grade B/C PHLF (4.8% vs. 8.3%, P =0.616), OS (median, unreached vs. unreached, P =0.94) and RFS (median, 26.7 vs. 17.1 months, P =0.096) were comparable between the two arms. In subgroup analyses, preoperative HAIC yield superior RFS (median, 26.7 vs. 16.2 months, P =0.042) in patients with baseline ICG-R15 less than or equal to 10%. CONCLUSION: Preoperative FOLFOX-HAIC caused apparent impairment of ICG clearance ability than TACE yet comparable impact on liver function and post-hepatectomy outcomes.

A novel NIR fluorescent probe inhibits melanoma progression through apoptosis and ERK/DRP1-mediated mitochondrial fission.

Melanoma, a highly metastatic malignant tumour, necessitated early detection and intervention. This study focuses on a hemicyanine fluorescent probe activated by near-infrared (NIR) light for bioimaging and targeted mitochondrial action in melanoma cells. IR-418, our newly designed hemicyanine-based NIR fluorescent probe, demonstrated effective targeting of melanoma cell mitochondria for NIR imaging. In vitro and in vivo experiments revealed IR-418's inhibition of melanoma growth through the promotion of mitochondrial apoptosis (Bax/Bcl-2/Cleaved Caspase pathway). Moreover, IR-418 inhibited melanoma metastasis by inhibiting mitochondrial fission through the ERK/DRP1 pathway. Notably, IR-418 mitigated abnormal ATL and ASL elevations caused by tumours without inflicting significant organ damage, indicating its high biocompatibility. In conclusion, IR-418, a novel hemicyanine-based NIR fluorescent probe targeting the mitochondria, exhibits significant fluorescence imaging capability, anti-melanoma proliferation, anti-melanoma lung metastasis activities and high biosafety. Therefore, it has significant potential in the early diagnosis and treatment of melanoma.

Clinical significance of preoperative CALLY index for prognostication in patients with esophageal squamous cell carcinoma undergoing surgery.

The C-reactive protein-albumin-lymphocyte (CALLY) index has been identified as a useful and sensitive predictive tool for stratification in cancers. This investigation aimed to validate the prognostic ability of CALLY in esophageal squamous cell carcinoma (ESCC). Clinical characteristics of 318 patients with ESCC who underwent radical excision were gathered and analyzed retrospectively. A restricted cubic spline (RCS) model was used to determine an ideal threshold of CALLY due to the non-linear relation. To investigate the predictors, Cox hazard regression analysis was used. The recursive partitioning analysis (RPA), a method of risk categorization, was also developed for prognostic prediction. The receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were used to distinguish from the traditional TNM stage. Patients were compared by groups according to the optimal threshold of CALLY index, which was depicted by the non-linear relation between the cancer-specific survival (CSS) and CALLY index (P < 0.0001). Compared to those with high CALLY index, patients with low CALLY index experienced significantly worse 5-year CSS (21.8% vs. 62.6%, P < 0.001). At different TNM stages, patients with high CALLY index also had better 5-year CSS (I: P = 0.029; II: P < 0.001; III: P < 0.001) in subgroup analyses. The hazard ratio for CSS was 0.368 and CALLY index was an independent predictive factor (P < 0.001). Using TNM stage and CALLY-based RPA algorithms, a new staging was created. The RPA model considerably outperformed the TNM classification for prognostication using ROC (P < 0.001). The DCA also demonstrated that the new model outperformed the TNM stage with significantly improved accuracy for CSS. The prognostic value of CALLY in ESCC undergoing radical resection was initially determined in this study. CALLY was substantially related to prognosis and might be utilized in conjunction with TNM to evaluate ESCC prior to surgery.

Lymph node ratio is a prognostic indicator for locally advanced esophageal squamous cell carcinoma after neoadjuvant immunochemotherapy.

The lymph node ratio (LNR) is regarded as a prognostic indicator in esophageal cancer (EC), but its applicability to neoadjuvant immunochemotherapy (NICT) in esophageal squamous cell carcinoma (ESCC) remains unexplored. This retrospective study, conducted between 2019 and 2021, analyzed ESCC patients who underwent radical esophagectomy following NICT. Patients were divided into two groups based on their LNR values according to the X-tile software: Low-LNR group (LNR 0-10%) and High-LNR group (LNR 10-100%). The association between LNR and clinical outcomes in ESCC after NICT were analyzed. A total of 212 ESCC patients who underwent surgery after NICT were included in this study, among which, 169 (79.7%) and 43 (20.3%) cases were allocated to the Low- and High-LNR groups, respectively. Pathologic complete response (PCR) was observed in 28.3% (60/212) of the overall cohort. Patients in the Low-LNR group demonstrated a significantly improved 3-year overall survival (OS) (81.7% vs 55.3%; P < 0.001) and disease-free survival (DFS) (79.9% vs 37.4%; P < 0.001). These findings were consistent among those with non-PCR (3-year DFS was 73.7% vs 37.4%; P < 0.001, and the 3-year OS was 78.9% vs 55.3%; P < 0.001, respectively). High LNR was associated with a 4.013-fold increased risk of relapse and a 7.026-fold elevated risk of death. Compared to the post-neoadjuvant therapy pathologic lymph nodes staging (ypN), LNR exhibited similar prognostic capabilities for DFS and OS. To the best of our knowledge, this study is the first to investigate the prognostic value of LNR in ESCC after NICT, suggesting that LNR may serve as a viable alternative to the ypN stage for prognostication in ESCC patients treated with NICT.

Casticin induces apoptosis and cytoprotective autophagy while inhibiting stemness involving Akt/mTOR and JAK2/STAT3 pathways in glioblastoma.

Glioblastoma (GBM) is the most common malignant glioma. However, the current systemic drugs cannot completely cure GBM. Casticin is a methoxylated flavonol compound isolated from a traditional Chinese medicine Vitex rotundifolia L.f. and exhibits a strong antitumor activity in multiple human malignancies. This study was aimed to explore the effects and underlying mechanisms of casticin in GBM. The MTT assay and colony formation was used to evaluate the casticin-induced cell viability in GBM cells. Apoptosis was assessed by ANNEXIV/PI staining assay. Autophagy was analyzed by transmission electron microscopy and immunofluorescence assays. GBM stem cell (GSC) was analyzed by tumor-sphere formation assay and ALDEFLUOR assay. The anti-GBM effect of casticin was also determined by the U87MG xenograft model. Casticin inhibited tumor cell growth in vitro and in vivo, as well as significantly induced apoptosis and autophagy. Autophagy inhibition augmented casticin-induced apoptosis. Casticin also reduced the GSC population by suppressing Oct4, Nanog, and Sox2. Mechanistically, casticin inhibited Akt/mTOR and JAK2/STAT3 signal pathways. The antitumor effect of casticin in GBM was demonstrated by inducing apoptosis, autophagy, and reducing population of GSCs; thus, it may be a potential GBM therapeutic agent for future clinical usage.

Pretreatment Pan-Immune-Inflammation Value (PIV) in Predicting Therapeutic Response and Clinical Outcomes of Neoadjuvant Immunochemotherapy for Esophageal Squamous Cell Carcinoma.

PURPOSE: The pan-immune-inflammation value (PIV), which reflects the balance between the host immune and inflammatory status, is a readily available index for evaluating cancer outcomes. Until now, however, no study has demonstrated the clinical response of PIV to neoadjuvant immunochemotherapy (NICT) in esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study included 218 patients with ESCC who underwent NICT. The relationship between PIV and therapeutic response (pathological complete response [PCR]) and clinical outcomes (overall survival [OS] and disease-free survival [DFS]) was examined. Cox proportional, hazard-regression analyses and the Kaplan-Meier method were used for survival analyses. Recursive partitioning analysis (RPA) was used to establish a novel risk stratification model. RESULTS: Sixty-six patients (30.3%) achieved PCR after NICT. Using PCR as the endpoint of interest, patients were compared in groups based on the optimal threshold. PIV was closely related to PCR (odds ratio [OR] 0.311, 95% confidence interval [CI] 0.140-0.690, P = 0.004). Compared with patients in the low PIV cohort, patients with high PIV had worse 3-year OS (58.7% vs. 83.6%, P < 0.001) and DFS (51.9% vs. 79.1%, P < 0.001). PIV was an independent predictor of OS (hazard ratio [HR] 2.364, 95% CI 1.183-4.724, P = 0.015) and DFS (HR 1.729, 95% CI 1.026-2.913, P = 0.040). Three risk groups with varied DFS and OS were staged by using an RPA method, and the prognostication accuracy was considerably improved. CONCLUSIONS: Pretreatment PIV can predict the therapeutic efficacy of NICT for ESCC. Because of better prognostic stratification, pretreatment PIV is a novel, sensitive, and effective indicator in ESCC receiving NICT. The prognostic results of PIV need to be verified in additional prospective studies.

Direct Laser Photocoagulation of the Retinal Pigment Epithelium: A Novel Method to Seal Retinal Breaks during Pars Plana Vitrectomy for Retinal Detachment.

BACKGROUND: This study evaluates the clinical effectiveness of employing direct retinal pigment epithelium (RPE) laser photocoagulation as a technique for achieving chorioretinal adhesion to effectively seal retinal breaks. METHODS: A total of 20 eyes from 20 patients were enrolled in the study; all selected eyes exhibited either rhegmatogenous or combined rhegmatogenous-tractional retinal detachment. During vitrectomy, direct RPE laser photocoagulation was executed, employing a power range of 100-150 mW and a duration of 120-200 ms, targeting the peripheries where the edges of each retinal break were anticipated to settle post-reattachment. This treated area's neuroretina thickness was compared to measurements obtained after conventional transretinal laser photocoagulation. RESULTS: Patients were followed for an average duration of 24 months, with a range of 11-46 months. A visible pigmentary reaction in the ophthalmoscopic examination was evident in the treated regions for all but one eye, where the retinal break was situated amidst myelinated nerve fibers. The study encountered no severe complications, and successful retinal reattachment was achieved in all 20 eyes. The mean best-corrected visual acuity (BCVA) at the final follow-up showed a statistically significant improvement compared to preoperative levels (p < 0.0001). A noteworthy difference in neuroretinal thickness was observed one-month post-surgery between areas treated with direct RPE and those treated with transretinal photocoagulation, measuring 217 µm and 104 µm, respectively. CONCLUSIONS: Our findings suggest that direct RPE laser photocoagulation is an effective therapeutic intervention for sealing retinal breaks.

Dietary tangeretin improved antibiotic-associated diarrhea in mice by enhancing the intestinal barrier function, regulating the gut microbiota, and metabolic homeostasis.

Antibiotic-associated diarrhea is mediated by antibiotic treatment and is usually caused by the disruption of the intestinal barrier, gut microbiota, and metabolic balance. To identify a dietary strategy that can mitigate the side effects of antibiotics, this study investigated the effect of tangeretin on antibiotic-associated diarrhea in C57BL/6 mice. The results revealed that dietary tangeretin significantly ameliorated symptoms of antibiotic-associated diarrhea, as evidenced by the decreased diarrhea status scores, the reduced fecal water content, the decreased caecum/body weight ratio, and the alleviated colonic tissue damage. Dietary tangeretin also exhibited a protective effect on the intestinal barrier function by upregulating the mRNA and protein expression of claudin-1 and ZO-1. Furthermore, analysis of the gut microbiota using 16S rRNA gene sequencing indicated that dietary tangeretin modulated the gut microbiota of mice with antibiotic-associated diarrhea via increasing the gut microbiota diversity and the abundance of beneficial bacteria, e.g., Lactobacillaceae and Ruminococcaceae, and decreasing the abundance of harmful bacteria, e.g., Enterococcus and Terrisporobacter. Additionally, dietary tangeretin restored the levels of short-chain fatty acids and modulated metabolic pathways by enriching purine metabolism, bile acid metabolism, ABC transporters, and choline metabolism in cancer. Collectively, these findings provide a solid scientific basis for the rational use of tangeretin as a preventive and therapeutic agent for antibiotic-associated diarrhea.

Global Scientific Trends in Virtual Reality for Pain Treatment From 2000 to 2022: Bibliometric Analysis.

Background: Virtual reality (VR) is a computer simulation technique that has been increasingly applied in pain management over the past 2 decades. Objective: In this study, we used bibliometrics to explore the literature on VR and pain control, with the aim of identifying research progress and predicting future research hot spots. Methods: We extracted literature on VR and pain control published between 2000 and 2022 from the Web of Science Core Collections and conducted bibliometric analyses. We analyzed the publication and citation trends in the past 2 decades, as well as publication and citation analyses of different countries, institutions, journals, and authors. For references, we conducted cocitation and burst analyses. For keywords, we conducted co-occurrence, clustering, timeline view, and citation burst analyses. Results: Based on 1176 publications, we found that there was a continuous increase in publication and citation volumes, especially in the last 5 years. The United States was the most representative country, and the University of Washington was the most representative institution, with both having the most publications and citations. The most popular journal in this field was Burns, and Hoffman HG was the most productive author, leading many studies on patients with burn pain. The reference with the most citation burst was a study on the verification of new hardware in pain control. The keywords with the highest citation bursts related to various situations of pain such as "burn pain," "wound care," "low back pain," and "phantom limb." Conclusions: VR has been applied in various clinical situations for pain management, among which burns and pediatric surgery have achieved satisfactory results. We infer that VR will be extended to more clinical pain situations in the future, such as pain control in wound care, low back pain, and phantom limb pain. New research hot spots will include the development of software and hardware to improve the immersive experience of VR for pain control. However, our work was based solely on English literature from the Web of Science database. For future studies, we recommend that researchers explore literature from multiple databases to enhance the scope of their research.

A novel immune-nutritional score predicts response to neoadjuvant immunochemotherapy after minimally invasive esophagectomy for esophageal squamous cell carcinoma.

Background: The role of neoadjuvant immunochemotherapy (NICT) has gradually attracted attention in recent years. To date, sensitive and reliable blood indicators to forecast the therapeutic response are still lacking. This study aimed to conduct a novel predictive score based on a variety of peripheral hematological immune-nutritional indicators to predict the therapeutic response in esophageal squamous cell carcinoma (ESCC) receiving NICT. Methods: There were 206 ESCC patients receiving NICT retrospectively recruited. With pathological complete response (pCR) as the dependent variable, independent risk variables of various peripheral blood immune-nutritional indexes were screened by logistic regression analyses to establish an integrative score. Results: By logical regression analyses, lymphocyte to monocyte ratio (LMR) and body mass index (BMI) were independent risk factors among all immune-nutritional indices. Then, an integrative score named BMI-LMR score (BLS) was established. Compared with BMI or LMR, BLS was related to complications, especially for respiratory complication (P=0.012) and vocal cord paralysis (P=0.021). Among all patients, 61 patients (29.6%) achieved pCR after NICT. BLS was significantly related to pCR [odds ratio (OR)=0.269, P<0.001)]. Patients in high BLS cohort demonstrated higher 3-year overall survival (OS) (89.9% vs. 67.9%, P=0.001) and disease-free survival (DFS) (81.2% vs. 62.1%, P=0.001). BLS served as an independent factor of DFS [hazard ratio (HR) =2.044, P =0.020) and OS (HR =2.960, P =0.019). Conclusion: The BLS, based on immune-nutritional indicators of BMI and LMR, employed as a straightforward, accurate, and useful indicator of pCR and prognostic prediction in ESCC patients undergoing NICT.

A Novel 7H-[1,2,4]Triazolo[3,4-b]thiadiazine-based Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Directed toward Treatment of Cystic Fibrosis.

Cystic fibrosis (CF) is an autosomal genetic disorder caused by disrupted anion transport in epithelial cells lining tissues in the human airways and digestive system. While cystic fibrosis transmembrane conductance regulator (CFTR) modulator compounds have provided transformative improvement in CF respiratory function, certain patients exhibit marginal clinical benefit or detrimental effects or have a form of the disease not approved or unlikely to respond using CFTR modulation. We tested hit compounds from a 300,000-drug screen for their ability to augment CFTR transepithelial transport alone or in combination with the FDA-approved CFTR potentiator ivacaftor (VX-770). A subsequent SAR campaign led us to a class of 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines that in combination with VX-770 rescued function of G551D mutant CFTR channels to approximately 400% above the activity of VX-770 alone and to nearly wild-type CFTR levels in the same Fischer rat thyroid model system.

Clinical utility of preoperative pan-immune-inflammation value (PIV) for prognostication in patients with esophageal squamous cell carcinoma.

BACKGROUND: Several researches have shown that pan-immune-inflammation value (PIV) is related to cancer prognosis in recent years. In esophageal squamous cell carcinoma (ESCC), nevertheless, the prognostic impact of PIV remains unclear. The present study sought to investigate the prognostic impact of preoperative PIV in ESCC with radical resection. METHODS: The data of 294 ESCC patients who received radical resection were retrospectively analyzed. Based on analyzing the non-linear relationship between PIV and cancer-specific survival (CSS), the optimal cutoff value for PIV was calculated by the restricted cubic spline (RCS) model. Cox proportional hazards regression was carried out to identify the prognostic factors. A risk stratification model was established by recursive partitioning analysis (RPA). The performance of the RPA-based model was assessed by the decision curve analysis (DCA) and receiver operating characteristic (ROC). RESULTS: The RCS visualized the non-linear relationship between PIV and CSS (P < 0.0001). Then patients were then divided into high and low groups based on the optimal threshold of 308.2. The 5-year CSS (17.7 % vs. 48.3 %, P < 0.001) was significantly worse in patients with high PIV than those in the low group. Subgroup analyses confirmed that patients with low PIV also achieved better 5-year survival at different pathological tumor node metastasis (pTNM) stages (pTNM I: P = 0.022; pTNM II: P = 0.001; pTNM III: P = 0.011). PIV served as an independent prognostic factor of CSS (hazard ratio = 1.983, P < 0.001). A new staging involving three risk groups with significantly different CSS was developed using RPA algorithms based on pTNM and PIV. Compared with the pTNM classification, the RPA-based model exhibited significantly superior performance for prognostication. CONCLUSION: The present study confirmed the prognostic impact of PIV in ESCC who treated with radical resection. PIV was associated with the tumor stage and prognosis, which might be useful in the preoperative assessment of ESCC.

Comprehensive nutritional index predicts clinical outcomes for esophageal squamous cell carcinoma receiving neoadjuvant immunotherapy combined with chemotherapy.

OBJECTIVE: No study has reported the clinical outcomes of comprehensive nutritional index (CNI) in esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy combined with chemotherapy (nICT). METHODS: This retrospective study involved 233 ESCC patients who underwent nICT. Principal component analysis was performed to establish the CNI based on 5 indexes including body mass index, usual body weight percentage, total lymphocyte count, albumin and hemoglobin. The relationships between the CNI and therapeutic response, postoperative complications and prognosis were analyzed. RESULTS: One hundred and forty-nine and 84 patients were assigned to the high and low CNI group, respectively. The incidences of respiratory complications (33.3% vs. 18.8%, P = 0.013) and vocal cord paralysis (17.9% vs. 8.1%, P = 0.025) in low CNI were significantly higher than those in high group, respectively. Seventy (30.0%) patients achieved pathological complete response (pCR). High CNI patients achieved a better pCR rate than those with low CNI (41.6% vs. 9.5%, P < 0.001). The CNI served as an independent pCR predictor [odds ratio (OR) = 0.167, 95% confidence interval (CI) = 0.074-0.377, P < 0.001)]. High CNI patients had better 3-year disease-free survival (DFS) (85.4% vs. 52.6%, P < 0.001) and overall survival (OS) (85.5% vs. 64.5%, P < 0.001) than those with low CNI, respectively. The CNI served as an independent prognostic score regarding DFS [hazard ratio (HR) = 3.878, 95% CI = 2.214-6.792, P < 0.001)] and OS (HR = 4.386, 95% CI = 2.006-9.590, P < 0.001). CONCLUSION: Based on nutrition-related indicators, the pretreatment CNI serves as a sensitive and effective predictor of therapeutic response, postoperative complications and prognosis in ESCC receiving nICT.

X-ray inhibits FUT4-mediated proliferation in A549 cells by downregulating SP1 expression.

Objective: To identify the mechanism of down-regulation of Lewis Y antigen caused by X-ray irradiation. METHODS: The present original research study was conducted at Zhejiang University City College, Hangzhou, Republic of China, from 2020 to 2022. Western blotting, Co-immunoprecipitation (CO-IP), electrophoretic mobility shift assay and Cell Counting Kit-8 (CCK8) were performed to confirm the effect of X-ray irradiation on A549 cell proliferation and its mechanism. Data was analysed using Statistical Package for Social Sciences (SPSS) 11.5. RESULTS: The expressions of fucosyltransferase IV and Lewis Y were decreased after X-ray irradiation, thus inhibiting the proliferation of A549 lung cancer cells. Deoxyribonucleic acid damage caused by the irradiation caused higher level of poly- adenosinediphosphate-ribosylated Specific Protein 1(SP1), and translocation of SP1 from the nucleus, decreasing the expression of fucosyltransferase IV and Lewis Y. Conclusion: There was a significant role of glycosylation in radiation therapy for lung cancer.

Prediction of pathologic complete response prediction in patients with locally advanced esophageal squamous cell carcinoma treated with neoadjuvant immunochemotherapy: A real-world study.

As an emerging hotspot for patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC), neoadjuvant immunochemotherapy (nICT) is safe and feasible. Pathological complete response (pCR) is considered to be an important therapeutic effect of neoadjuvant therapy. However, few studies have explored pCR predictors for nICT in LA-ESCC. The purpose of this study was to predict pCR after nICT in LA-ESCC by pretreatment clinical characteristics and hematological indexes. The primary endpoint was to explore the impacts on the predictors for pCR prediction. Clinical characteristics and hematological indexes including systemic immune-inflammation index (SII), neutrophil lymphocyte ratio (NLR), lymphocyte monocyte ratio (LMR), prognostic nutritional index (PNI) and platelet lymphocyte ratio (PLR) were conducted. A total of 150 LA-ESCC patients were enrolled in the current study. There were 14 (9.3%) female and 136 (90.7%) male patients. Fifty-two patients achieved pCR (34.7%). A higher pCR rate was found in low-NLR group (43.7% vs. 26.6%, P=0.028) and high-LMR group (43.8% vs. 21.3%, P=0.004), respectively. Differentiation [odds ratio (OR) =0.464, 95% confidence interval (CI)=0.259-0.830, P=0.010], LMR (OR=0.309, 95% CI=0.132-0.707, P=0.007) and cTNM (OR=0.225, 95% CI=0.115-0.441, P<0.001) were independent predictors for pCR. The nomogram for pCR prediction based on LMR, differentiation and cTNM stage had good discrimination performance and calibration coordination (C-index=0.779). The results of our study are of great significance for designing therapeutic strategies. Nomogram based on LMR, differentiation and cTNM may accurately and effectively predict pCR.

The usefulness of pretreatment controlling nutritional status score for predicting recurrence in patients with esophageal squamous cell carcinoma undergoing neoadjuvant immunochemotherapy: A real-world study.

Background: The controlling nutritional status (CONUT) score, as an immune-nutritional index, has been reported to be related to prognosis in several cancers. Neoadjuvant immunochemotherapy (nICT) is an emerging pattern for cancer treatment in recent years. However, the usefulness of CONUT in esophageal squamous cell carcinoma (ESCC) with nICT has not been reported so far. This study attempted to clarify the usefulness of CONUT in predicting disease-free survival (DFS) in ESCC with nICT. Methods: Two hundred sixteen ESCC patients receiving nICT between 2019 and 2021 were retrospectively enrolled. Based on CONUT, the patients were divided into two groups: low groups (score ≤ 2) and high (score ≥ 3) groups. The relationships between CONUT and clinical characteristics were estimated. Cox regression analyses with hazard ratios (HRs) and 95% confidence intervals (CIs) were also performed to evaluate the prognostic factors of DFS. Results: Fifty-nine (27.3%) patients achieved pathologic complete response (pCR), and 30 (13.9%) cases had a recurrence. There were 150 cases (69.4%) in low CONUT group and 66 cases (30.6%) in high CONUT group, respectively. The results revealed that vessel invasion (P = 0.037), postoperative pneumonia (P = 0.001), advanced ypT stage (P = 0.011), cTNM stage (P = 0.007), and ypTNM stage (P < 0.001) were significantly related to patients with a high CONUT score. A high pCR rate was found in patients with a low CONUT score (33.3% vs. 13.6%, P = 0.003), and a high recurrence rate was found in patients with a high CONUT score (24.2% vs. 9.3%, P = 0.004), respectively. Patients with a low CONUT score had a better 1-year DFS than those with a high CONUT score (90.7% vs. 75.8%, P = 0.004). Multivariate analyses indicated that the pretreatment CONUT score was an independent predictor regarding DFS (HR = 2.221, 95% CI: 1.067-4.625, P = 0.033). Conclusion: A better response and a lower recurrence were found in ESCC patients with a lower pretreatment CONUT. As a useful index for immune-nutritional status, the CONUT might be a reliable prognostic indicator in ESCC patients with nICT.