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Abstract Background Several inflammatory indicators have been reported to have predictive value in many types of malignant cancer. This research was aimed to explore the ability of the monocyte-to-lymphocyte ratio (MLR) to predict prognosis in patients with intrahepatic cholangiocarcinoma (ICC) who subjected to curative hepatectomy. Methods This retrospective analysis included 196 patients with ICC who underwent curative hepatectomy between May 2018 and April 2023. The predictive abilities of the preoperative MLR in assessing overall survival (OS) and disease-free survival (DFS) in those patients were compared with other inflammation-based scores, including monocyte-to-white ratio, neutrophil-to-lymphocyte ratio, neutrophil-to-white ratio, platelet-to-lymphocyte ratio, platelet-to-white ratio, and systemic immune-inflammation index, as well as tumor markers, like carcinoembryonic antigen (CEA) and carbohydrate antigen 19 − 9 (CA19-9). Results The area under the time-dependent receiver operating characteristic curve indicated that the preoperative MLR had higher predictive efficiency in contrast with other inflammation-based scores and tumor markers in assessing OS and DFS. Stratifying patients according to the optimal cut-off value for the preoperative MLR, the data showed that both OS and DFS in the high MLR group were significantly worse than those in the low MLR group (p

A new loach species, Oreonectes zhangi sp. nov., was identified from Xingye County, Yulin City, Guangxi, China. The species can be distinguished from all other congeners by a combination of the following characters: six branched pelvic-fin rays; a reduced posterior chamber of air-bladder; vertebrae 4 + 32; the tip of the male pelvic fin does not reach the anus. Molecular analyses using the Cyt b gene showed that the new species forms a monophyletic group and is closely related to O. damingshanensis.

Objectives: Combination therapy of lenvatinib and immune checkpoint inhibitors (CLICI) has emerged as a promising approach for managing unresectable hepatocellular carcinoma (HCC). However, the response to such treatment is observed in only a subset of patients, underscoring the pressing need for reliable methods to identify potential responders. Materials & methods: This was a retrospective analysis involving 120 patients with unresectable HCC. They were divided into training (n = 72) and validation (n = 48) cohorts. We developed an interpretable deep learning model using multiphase computed tomography (CT) images to predict whether patients will respond or not to CLICI treatment, based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). We evaluated the models' performance and analyzed the impact of each CT phase. Critical regions influencing predictions were identified and visualized through heatmaps. Results: The multiphase model outperformed the best biphase and uniphase models, achieving an area under the curve (AUC) of 0.802 (95% CI = 0.780–0.824). The portal phase images were found to significantly enhance the model's predictive accuracy. Heatmaps identified six critical features influencing treatment response, offering valuable insights to clinicians. Additionally, we have made this model accessible via a web server at http://uhccnet.com/ for ease of use. Conclusions: The integration of multiphase CT images with deep learning-generated heatmaps for predicting treatment response provides a robust and practical tool for guiding CLICI therapy in patients with unresectable HCC.

Abstract Introduction Small Cell Lung Cancer (SCLC) can be classified into transcriptional subtypes with distinct degrees of neuroendocrine (NE) differentiation. Recent evidence supports plasticity among subtypes with a bias toward adoption of low-NE states during disease progression or upon acquired chemotherapy resistance. Here, we identify a role for SMARCA4, the catalytic subunit of the SWI/SNF complex, as a regulator of subtype shift in SCLC. Methods ATACseq and RNAseq experiments were performed in SCLC cells after pharmacological inhibition of SMARCA4. DNA binding of SMARCA4 was characterized by ChIPseq in high-NE SCLC patient derived xenografts (PDXs). Enrichment analyses were applied to transcriptomic data. Combination of FHD-286 and afatinib was tested in vitro and in a set of chemo-resistant SCLC PDXs in vivo. Results SMARCA4 expression positively correlates with that of NE genes in both SCLC cell lines and patient tumors. Pharmacological inhibition of SMARCA4 with FHD-286 induces the loss of NE features and downregulates neuroendocrine and neuronal signaling pathways while activating non-NE factors. SMARCA4 binds to gene loci encoding NE-lineage transcription factors ASCL1 and NEUROD1 and alters chromatin accessibility, enhancing NE programs. Enrichment analysis applied to high-confidence SMARCA4 targets confirmed neuron related pathways as the top GO Biological processes regulated by SMARCA4 in SCLC. In parallel, SMARCA4 also controls REST, a known suppressor of the NE phenotype, by regulating SRRM4-dependent REST transcript splicing. Furthermore, SMARCA4 inhibition drives ERBB pathway activation in SCLC, rendering SCLC tumors sensitive to afatinib. Conclusions This study nominates SMARCA4 as a key regulator of the NE state plasticity and defines a novel therapeutic strategy for SCLC.

Abstract Aim Compared to the conventional cardiopulmonary resuscitation (CCPR), potential benefits of extracorporeal cardiopulmonary resuscitation (ECPR) for patients with cardiac arrest (CA) are still controversial. We aimed to determine whether ECPR can improve the prognosis of CA patients compared with CCPR. Methods We systematically searched PubMed, EMBASE, and Cochrane Library from database’s inception to July 2023 to identify randomized controlled trials (RCTs) or cohort studies that compared ECPR with CCPR in adults (aged ≥ 16 years) with out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). This meta-analysis was performed using a random-effects model. Two researchers independently reviewed the relevance of the study, extracted data, and evaluated the quality of the included literature. The primary outcome was short-term (from hospital discharge to one month after cardiac arrest) and long-term (≥ 90 days after cardiac arrest) survival with favorable neurological status (defined as cerebral performance category scores 1 or 2). Secondary outcomes included survival at 1 months, 3–6 months, and 1 year after cardiac arrest. Results The meta-analysis included 3 RCTs and 14 cohort studies involving 167,728 patients. We found that ECPR can significantly improve good neurological prognosis (RR 1.82, 95%CI 1.42–2.34, I2 = 41%) and survival rate (RR 1.51, 95%CI 1.20–1.89, I2 = 62%). In addition, the results showed that ECPR had different effects on favorable neurological status in patients with OHCA (short-term: RR 1.50, 95%CI 0.98- 2.29, I2 = 55%; long-term: RR 1.95, 95% CI 1.06–3.59, I2 = 11%). However, ECPR had significantly better effects on neurological status than CCPR in patients with IHCA (short-term: RR 2.18, 95%CI 1.24- 3.81, I2 = 9%; long-term: RR 2.17, 95% CI 1.19–3.94, I2 = 0%). Conclusions This meta-analysis indicated that ECPR had significantly better effects on good neurological prognosis and survival rate than CCPR, especially in patients with IHCA. However, more high-quality studies are needed to explore the role of ECPR in patients with OHCA.

Abstract Neuroendocrine (NE) transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor prognosis. Up to date, even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53 (TP53) and Retinoblastoma Transcriptional Corepressor 1 (RB1) mutations in their tumors, no therapeutic strategies are available to prevent or delay histological transformation. Upregulation of the cell cycle kinase Cell Division Cycle 7 (CDC7) occurred in tumors during the initial steps of NE transformation, already after TP53/RB1 co-inactivation, leading to induced sensitivity to the CDC7 inhibitor simurosertib. CDC7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen (MYC), implicated in stemness and histological transformation. Ectopic overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy, even in the presence of simurosertib. CDC7 inhibition also markedly extended response to standard cytotoxics (cisplatin, irinotecan) in lung and prostate small cell carcinoma models. These results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity, as well as to effectively treat NE tumors de novo or after transformation. As simurosertib clinical efficacy trials are ongoing, this concept could be readily translated for patients at risk of transformation.

Background/Aims The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD). Methods This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity-specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD, and non-MAFLD HCC. Results 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% confidence interval [CI] 34.5–63.0%) and 12.4% (95% CI 8.3–17.3%), respectively. In HCC due to chronic hepatitis B, C, and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI 30.2–50.3%), 54.1% (95% CI 40.4–67.6%) and 64.3% (95% CI 52.7–75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC. Conclusions MAFLD is common as a sole aetiology, but more so as a co-factor in mixed-aetiology HCC, supporting the use of positive diagnostic criteria.

Abstract P-type Fe3CoSb12-based skutterudite thin films are successfully fabricated, exhibiting high thermoelectric performance, stability, and flexibility at medium-to-high temperatures, based on preparing custom target materials and employing advanced pulsed laser deposition techniques to address the bonding challenge between the thin films and high-temperature flexible polyimide substrates. Through the optimization of fabrication processing and nominal doping concentration of Ce, the thin films show a power factor of >100 μW m−1 K−2 and a ZT close to 0.6 at 653 K. After >2000 bending cycle tests at a radius of 4 mm, only a 6 % change in resistivity can be observed. Additionally, the assembled p-type Fe3CoSb12-based flexible device exhibits a power density of 135.7 µW cm−2 under a temperature difference of 100 K with the hot side at 623 K. This work fills a gap in the realization of flexible thermoelectric devices in the medium-to-high-temperature range and holds significant practical application value.

Abstract Aims This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. Methods Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. Results Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. Conclusion Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

AimComparing the safety, effectiveness, and mid-term survival rates of robot-assisted minimally invasive esophagectomy (RAMIE) and video-assisted minimally invasive esophagectomy (VAMIE).MethodsA total of 842 patients undergoing minimally invasive esophagectomy were analyzed, including 694 patients in VAMIE group and 148 in RAMIE group. PSM analysis was applied to generate matched pairs for further comparison. Operative outcomes, postoperative complications and Mid-term outcomes were compared between all patients in matched groups.ResultsAfter 1:4 PSM, 148 patients in the RAMIE and 592 patients in the VAMIE. Compared to VAMIE, RAMIE exhibited earlier removal of chest and neck drainage tubes, shorter postoperative hospital stays, and a higher number of lymph node dissections. However, the surgical duration of RAMIE was longer than that of VAMIE. Postoperative complications were no statistically significant between the RAMIE and VAMIE groups. There was no statistically significant difference in the 3-year OS and DFS between the two groups.ConclusionCompared to VAMIE, RAMIE emerges as a viable and safe surgical approach and suggests RAMIE as a potential alternative to minimally invasive esophagectomy.

BackgroundGestational diabetes mellitus (GDM) significantly affects the fetal metabolic environment, elevating risks of neonatal hypoglycemia and macrosomia. Metabolomics offers promising avenues for early prediction and diagnosis of GDM and associated adverse offspring outcomes.MethodsThis study analyzed serum samples from pregnant women diagnosed with GDM at 24 to 28 weeks of gestation using untargeted metabolomics. We monitored the health outcomes of their offspring to explore the correlation between initial serum metabolite profiles and subsequent health outcomes, to uncover the predictive markers for hypoglycemia and macrosomia in these offspring.ResultsOut of 200 participants, 154 had normal newborns, 33 had offspring with hypoglycemia, and 19 had offspring with macrosomia. From 448 identified metabolites, 66 showed significant differences in cases of hypoglycemia, and 45 in macrosomia. A panel of serum metabolite biomarkers achieved Area Under the Curve (AUC) values of 0.8712 for predicting hypoglycemia and 0.9434 for macrosomia.ConclusionThe study delineated metabolic disruptions in GDM during 24–28 weeks of gestation and pinpointed biomarkers capable of forecasting adverse neonatal outcomes. These findings could inform GDM management strategies and minimize the incidence of such outcomes.

IntroductionImmune-related epidermal necrolysis (irEN), including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), represents a potentially lethal reaction to immune checkpoint inhibitors. An optimal treatment strategy remains undefined. This study evaluates the effectiveness and safety of combination therapy with corticosteroids and tumor necrosis factor inhibitors (TNFi) in treating irEN patients.MethodsIn this single-center, prospective, observational study, patients with irEN received either corticosteroid monotherapy or a combination therapy of corticosteroids and TNFi (etanercept for SJS, infliximab for TEN). The primary endpoint was re-epithelization time, with secondary endpoints including corticosteroid exposure, major adverse event incidence, acute mortality rates, and biomarkers indicating disease activity and prognosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100051052).ResultsThirty-two patients were enrolled (21 SJS, 11 TEN); 14 received combination therapy and 18 received corticosteroid monotherapy. IrEN typically occurred after 1 cycle of ICI administration, with a median latency of 16 days. Despite higher SCORTEN scores in the combination group (3 vs. 2, p = 0.008), these patients experienced faster re-epithelization (14 vs. 21 days; p < 0.001), shorter corticosteroid treatment duration (22 vs. 32 days; p = 0.005), and lower prednisone cumulative dose (1177 mg vs. 1594 mg; p = 0.073). Major adverse event rates were similar between groups. Three deaths occurred due to lung infection or disseminated intravascular coagulation, with mortality rates for both groups lower than predicted. Potential risk factors for increased mortality included continuous reduction in lymphocyte subset counts (CD4+ T cells, CD8+ T cells, natural killer cells) and consistent rises in inflammatory markers (serum ferritin, interleukin-6, TNF-α). Re-epithelization time negatively correlated with body mass index and positively correlated with epidermal detachment area and serum levels of interleukin-6 and TNF-α.ConclusionsCorticosteroids combined with TNFi markedly promote re-epithelization, reduce corticosteroid use, and decrease acute mortality in irEN patients without increasing major adverse events, offering a superior alternative to corticosteroid monotherapy. Inflammatory markers and lymphocyte subsets are valuable for assessing disease activity and prognosis.

Abstract Introduction The necessity for tuberculosis preventive treatment (TPT) and routine T-SPOT.TB monitoring in patients with psoriasis and tuberculosis infection (TBI) undergoing interleukin (IL)-17A inhibitor therapy remains uncertain. This study aims to evaluate the long-term safety of IL-17A inhibitors administered without TPT and analyze changes in T-SPOT.TB among these patients. It also identifies risk factors for TBI in patients with psoriasis. Methods This single-center prospective study enrolled adult patients with plaque psoriasis and TBI receiving IL-17A inhibitors. TBI was defined as positive T-SPOT.TB results (≥ 6 spots) without symptoms or evidence of active tuberculosis (ATB). TPT administration was based on contraindications, tuberculosis risk factors, and patient preferences. The primary endpoint was the incidence of ATB over 2 years. Secondary outcomes included T-SPOT.TB changes and TBI risk factors. Results Of the 129 patients with psoriasis and TBI enrolled in the study, 97 (75.2%) did not receive TPT, while 32 (24.8%) did. Among them, 109 patients (84.5%) completed the 2-year follow-up. During the 235 person-years of observation, no ATB cases were identified. Median T-SPOT.TB values showed no significant changes from baseline to year 2 in both the non-TPT (20 vs. 17 spots, p = 0.975) and TPT groups (55 vs. 58 spots, p = 0.830). T-SPOT.TB reversed in 14 patients (12.8%), mostly in the non-TPT group. Moreover, for TBI risk factor analysis, a cohort of 212 patients with psoriasis with negative baseline T-SPOT.TB was evaluated, revealing a TBI prevalence of 37.8%. Logistic regression analysis highlighted age ≥ 45 years (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.50–3.99, p