e16190 Background: The prognosis of advanced intrahepatic cholangiocarcinoma (ICC) remains unsatisfactory with current gemcitabine-based chemotherapy in combination with PD-1/PD-L1 inhibitors. This study aimed to investigate the efficacy and safety of aderbrelimab (PD-L1 inhibitor) and lenvatinib in combination with gemcitabine and cisplatin as first-line treatment in advanced and unresectable ICC patients. Methods: This prospective, single-arm, multicenter, phase II study included treatment-naive adult (≥18 years) patients with unresectable and advanced ICC. All patients received 1200mg aderbrelimab Q3W via intravenous (IV) infusion, 8mg lenvatinib QD orally, and 1g/m² gemcitabine plus 25 mg/m² cisplatin on Day 1 and Day 8, Q3W by IV for 6 cycles, followed by maintenance aderbrelimab and lenvatinib until disease progression (PD) or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). The secondary endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and safety. Results: Between April 2024 and November 2025, 26 pathologically-confirmed advanced ICC patients with a median age of 60.5 (range, 45-78) years, including 20 men (76.9%), were enrolled at five centers. At the end of last follow-up (January 20, 2026), the ORR was 46. 2% (12/26; 95% CI: 26.6%-66.6%), and disease control rate (DCR) was 92.3% (24/26; 95% CI:74.9%-99.1%). Median follow-up time was 8.1 months. 12 patients experienced disease progression and 4 patients have died. The median PFS was 8.5 months. The median OS have not been reached. The most common grade 3 or 4 treatment-related adverse events (TRAEs) were neutropenia and thrombocytopenia observed in 6 (23.1%) and 5 (19.2%) patients, respectively. No unacceptable toxicity or treatment-related deaths occurred. Conclusions: Aderbrelimab and lenvatinib in combination with gemcitabine and cisplatin showed promising efficacy with reasonable tolerability in advanced ICC patients. Survival data is immature and will be updated in the future. Clinical trial information: NCT06298968 .

This study aimed to evaluate the efficacy of thunder‑fire moxibustion (TFM) for cancer‑related fatigue (CRF) in patients with Qi stagnation and blood stasis syndrome undergoing chemotherapy for colorectal cancer. In this randomized controlled trial, 77 patients with colorectal cancer undergoing chemotherapy were randomly assigned to either a control group (conventional care) or an experimental group (conventional care plus thunder-fire moxibustion, TFM). Both groups received two treatment courses, with five intervention sessions per course. The primary outcome was the change in Revised Piper Fatigue Scale (RPFS) scores. Secondary outcomes included sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI), quality of life measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Traditional Chinese Medicine (TCM) syndrome scores, routine blood indicators, and inflammatory factor levels.Assessments were conducted before and after two intervention cycles and during a follow-up period. Thunder‑fire moxibustion may be an effective supportive intervention for reducing fatigue and improving sleep and quality of life in patients with colorectal cancer undergoing chemotherapy. This study was registered on February 11, 2025, at the International Traditional Medicine Clinical Trial Registry (Registration Number: ITMCTR2025000305).

Objective: To evaluate the effectiveness and safety of Shenyi Capsule (SC) combined with conventional anticancer therapies through a comprehensive assessment of systematic reviews/meta-analyses (SRs/MAs), identify limitations in current evidence, and provide evidence-based guide for clinical practice and research. Methods: Registered in PROSPERO (CRD42024573610), this study searched 8 Databases from inception to November 10, 2024. Two separate reviewers were responsible for selecting studies, collecting data, assessing quality, and evaluating the potential for bias, with this research incorporating only SRs/MAs based on randomized controlled trials and utilizing 4 tools (AMSTAR-2, PRISMA 2020, ROBIS, GRADE) to evaluate methodological quality and risk of bias. Results: Thirteen SRs/MAs were included, focusing on 4 cancer types. AMSTAR-2 evaluations revealed no high quality studies. Compliance with PRISMA 2020 guidelines was below 50% for most items, with major deficiencies including lack of protocol registration, incomplete abstracts and search strategies, inappropriate or missing risk-of-bias assessments, insufficient descriptions of data transformation methods, absence of heterogeneity and sensitivity analyses, and failure to report funding sources. ROBIS indicated high bias risk in 11 studies. GRADE assessment of 109 outcomes showed evidence quality as moderate (40.37%), low (34.86%), or very low (24.77%). Discussion: SC may enhance efficacy and safety as an adjuvant cancer therapy. However, methodological flaws in existing SRs/MAs limit reliability. Future research should prioritize standardized SR/MA protocols and RCT designs to improve evidence quality, reduce bias, and strengthen clinical applicability.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, associated with high morbidity and mortality worldwide. Despite advancements in diagnostic methods and systemic treatments, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), the development of drug resistance remains a significant challenge in HCC management. Traditional treatments such as surgical resection and transarterial chemoembolization offer limited efficacy, especially in advanced stages. Although novel therapies like lenvatinib, sorafenib, regorafenib, and ICIs have shown promise, their effectiveness is often hindered by primary and acquired resistance, leading to poor long-term survival outcomes. This review focuses on the molecular mechanisms underlying resistance to targeted therapies and immunotherapies in HCC. Key factors contributing to resistance include alterations in the tumor microenvironment (TME), immune evasion, hypoxia, changes in cellular metabolism, and genetic mutations. Additionally, molecular players such as ferroptosis, autophagy, apoptosis, endoplasmic reticulum stress, ABC transporters, and non-coding RNAs(ncRNAs) are discussed as contributors to drug resistance. Understanding these mechanisms is critical for the development of novel therapeutic strategies aimed at overcoming resistance, improving patient outcomes, and ultimately enhancing survival rates in HCC patients.

Background Fuzheng Kang'ai Formula (FZKA) is a clinically effective traditional Chinese medicine compound with demonstrated efficacy against non-small cell lung cancer (NSCLC). This study systematically investigated its anti-tumor mechanisms, focusing on the interplay between autophagy and ferroptosis. Purpose We aimed to determine whether FZKA suppresses NSCLC through autophagy-ferroptosis crosstalk and to identify key epigenetic regulators involved in this process. Study Design The study combined in vitro assays using NSCLC cell lines with in vivo validation via subcutaneous xenograft models. Methods : An Agilent 6546 LC/Q-TOF liquid chromatography-mass spectrometry system was used to detect the stability of component contents in FZKA across different batches. Autophagy was assessed through mRFP-GFP-LC3 adenovirus assay, transmission electron microscopy, and LC3B-II/I conversion. Ferroptosis was evaluated by measuring lipid peroxidation and intracellular Fe²⁺ levels. Crosstalk was examined using autophagy and ferroptosis inhibitors to monitor reciprocal effects on SLC7A11 and p-mTOR. EZH2 was investigated as an upstream regulator of mTOR and SLC7A11. Protein and mRNA expression were analyzed by Western blot and qRT-PCR. EZH2-overexpressing cells were established to evaluate functional rescue, and lysine methylation label-free quantitative proteomics was employed to identify downstream effectors. A nude mouse xenograft model was used for in vivo validation, with tumor weight and volume measured, and key proteins analyzed. Results The composition of FZKA remains stable across different batches. FZKA induced autophagy via mTOR suppression and Beclin1 upregulation, while promoting ferroptosis through SLC7A11 and GPX4 inhibition. Functional crosstalk was confirmed through inhibitor experiments showing mTOR and SLC7A11 as key mediators. FZKA significantly reduced EZH2 expression, and EZH2 overexpression partially reversed the effects of FZKA on mTOR and SLC7A11. Proteomic analysis revealed DOT1L/H3K79me2 as a downstream pathway of FZKA-mediated EZH2 regulation. DOT1L expression correlated with EZH2 levels, and EZH2 overexpression rescued DOT1L/H3K79me2 suppression. These results were consistently verified in vivo. Conclusion FZKA suppresses NSCLC by regulating the EZH2/DOT1L/H3K79me2 signaling to induce crosstalk between mTOR-mediated autophagy and SLC7A11-dependent ferroptosis, leading to extensive cell death. This study reveals a novel epigenetic mechanism coordinating two cell death pathways and supports FZKA's clinical application.

Tumor-associated macrophages (TAMs) are crucial in hepatocellular carcinoma (HCC) development and invasion. This study explores monocyte/ macrophage-associated gene expression profiles in HCC, constructs a prognostic model based on these genes, and examines its relationship with drug resistance and immune therapy responses. Single-cell RNA sequencing(scRNA-seq) data from 10 HCC tissue biopsy samples, totaling 24,597 cells, were obtained from the GEO database to identify monocyte/macrophage-associated genes. A prognostic model was constructed and validated using external datasets and Western blot. Relationships between the model, clinical correlates, drug sensitivity, and immune therapy responses were investigated. From scRNA-seq data, 2,799 monocyte/macrophage marker genes were identified. Using the TCGA dataset, a prognostic model based on the single-gene UQCRH was constructed, stratifying patients into high-risk and low-risk groups based on overall survival rates. High-risk group patients showed reduced survival rates and higher UQCRH expression in tumor tissues. Western blot analysis further confirmed the elevated expression of UQCRH in HCC cell lines. Spatial transcriptomics analysis revealed that high UQCRH expression co-localized with malignant cells in the tumor tissue. Drug sensitivity analysis revealed that the high-risk group had lower sensitivity to sorafenib and axitinib. Immune therapy response analysis indicated poorer outcomes in the high-risk group, with more pronounced APC inhibition and a weaker IFN-II response. Clinical indicator analysis showed a positive correlation between high UQCRH expression and tumor invasion. Enrichment analysis of UQCRH and associated molecules indicated involvement in oxidative phosphorylation and mitochondrial electron transport. This study introduces a prognostic model for HCC patients based on monocyte/macrophage marker genes. The single-gene model predicts HCC patient survival and treatment outcomes, identifying high-risk individuals with varying drug sensitivities and immune suppression states.

Reprogramming of cancer metabolism has become increasingly concerned over the last decade, particularly the reprogramming of glucose metabolism, also known as the ''Warburg effect''. The reprogramming of glucose metabolism is considered a novel hallmark of human cancers. A growing number of studies have shown that reprogramming of glucose metabolism can regulate many biological processes of cancers, including carcinogenesis, progression, metastasis, and drug resistance. In this review, we summarize the major biological functions, clinical significance, potential targets and signaling pathways of glucose metabolic reprogramming in human cancers. Moreover, the applications of natural products and small molecule inhibitors targeting glucose metabolic reprogramming are analyzed, some clinical agents targeting glucose metabolic reprogramming and trial statuses are summarized, as well as the pros and cons of targeting glucose metabolic reprogramming for cancer therapy are analyzed. Overall, the reprogramming of glucose metabolism plays an important role in the prediction, prevention, diagnosis and treatment of human cancers. Glucose metabolic reprogramming-related targets have great potential to serve as biomarkers for improving individual outcomes and prognosis in cancer patients. The clinical innovations related to targeting the reprogramming of glucose metabolism will be a hotspot for cancer therapy research in the future. We suggest that more high-quality clinical trials with more abundant drug formulations and toxicology experiments would be beneficial for the development and clinical application of drugs targeting reprogramming of glucose metabolism.This review will provide the researchers with the broader perspective and comprehensive understanding about the important significance of glucose metabolic reprogramming in human cancers.

Moutan cortex has demonstrated antitumor properties attributed to its bioactive compound Paeoniflorigenone (PA). Nevertheless, there is limited research on the efficacy of PA in the prevention and treatment of hepatocellular carcinoma (HCC). We aimed to investigate the potential pharmacological mechanisms of PA in the treatment of Aflatoxin B1 (AFB1)-induced hepatocarcinogenesis using network pharmacology and bioinformatics analysis approaches. Through various databases and bioinformatics analysis approaches, 34 shared targets were identified as potential candidate genes for PA in fighting liver cancer caused by AFB1. Pathway analysis revealed involvement in cell cycle, HIF-1, and Rap1 pathways. A risk assessment model was developed using LASSO regression, showing an association between the identified genes and the tumor immune microenvironment. The genes within the risk model were found to be linked to the immune response in liver cancer. Molecular docking studies indicated that PA interacts with its targets through hydrogen bonding and hydrophobic interactions. This study provides insights into the possible mechanisms of PA in liver cancer treatment and offers a predictive model for assessing the risk level of individuals with liver cancer. These findings have significant implications for the therapeutic strategies in managing liver cancer patients.

OBJECTIVE:The purpose of this overview is to assess systematic reviews (SRs)/ meta-analyses (MAs) of Huachansu (HCS) combination chemotherapy for treating non-small cell lung cancer (NSCLC) and provide summarized evidence for clinical decision making.METHODS:From the creation of the database to JUNE 2023, 8 databases in English and Chinese were searched. SRs/MAs that met the inclusion and exclusion criteria were included. Two reviewers independently screened research, extracted data and assessed methodological quality, risk of bias, report quality and evidence quality by using relevant criteria from AMSTAR-2, ROBIS scale, PRISMA, and GRADE system.RESULTS:The short-term effect, long-term effect, quality of life improvement, safety and pain relief effect in 8 included SRs/MAs were assessed in this overview according to quantitative synthesis. Results assessed by AMSTAR-2, PRISMA, and ROBIS were generally unsatisfactory, with the results of the AMSTAR-2 assessment showing that all of them were of low or critically low quality; the number of items in the included research that were fully reported (compliance was 100%) by the PRISMA checklist was only 50%, while there were 38.10% of the research reporting less than 60% completeness; the ROBIS assessment showed a small number of systems to be low risk of bias. In addition, 26 items were rated as moderate quality, while 50.94% of items were rated as low or critically low quality by GRADE.CONCLUSION:HCS may be a promising adjuvant therapy for NSCLC. However, high-quality SRs/MAs and randomized control trials (RCTs) should be conducted to provide sufficient evidence so as to draw a definitive conclusion.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is an uncommon subtype of lung cancer with bleak prognosis. Its optimal treatment remains undetermined due to its malignancy. A 66-year-old man diagnosed with unresectable locally advanced LCNEC exhibited partial radiographic response to chemo-immunotherapy. He underwent salvage surgery after 4 rounds of docetaxel/nedaplatin (DP) regimen plus sintilimab, a highly selective monoclonal antibody which targets human anti-programmed death-ligand 1 (PD-L1). In addition, the pathologic examination of the excision demonstrated that there were no viable residuary tumor cells. This case indicates that neoadjuvant chemo-immunotherapy might benefit patients with locally advanced LCNEC, which deserves further investigation.

BACKGROUND:Conflicting results about the effect of concomitant medications on immunotherapy in non-small cell lung cancer (NSCLC) were reported by many meta-analyses (MAs), and the certainty of evidence linking concomitant medications with immunotherapy efficacy has not been quantified, which may cause some evidence to be misinterpreted. METHODS:Four databases including Embase, Cochrane Library, PubMed, and Web of Science were searched from inception to January 2023 in English. Based on prospective or retrospective clinical controlled trials including immunotherapy with concomitant medications or not in NSCLC, quantitative MAs reporting the efficacy of immunotherapy with binary direct comparison and enough extractable data were collected. The methodological quality, reporting quality, and risk of bias of included MAs were evaluated respectively. New meta-analyses were conducted and their evidence certainty was classified as nonsignificant, weak, suggestive, highly suggestive, or convincing. RESULTS:Fifteen MAs with 5 medications were included. After being assessed by AMSTAR-2, PRISMA, and ROBIS, the major shortcomings were focused on the registration of protocol, literature retrieval or data extraction, implementation of sensitivity analysis or evidence certainty assessment, and incomplete reporting in the section of method and result. New pooled analyses indicated that antibiotics (HR = 1.545[1.318-1.811]), steroids (HR = 1.784[1.520-2.093]), proton pump inhibitors (PPIs) (HR = 1.303[1.048-1.621]) and opioids (HR = 1.910[1.213-3.006]) could shorten overall survival (OS) in patients with NSCLC receiving immunotherapy. Besides, antibiotics (HR = 1.285[1.129-1.462]) and steroids (HR = 1.613[1.315-1.979]) were harmful to progression-free survival (PFS) in these patients significantly. No negative effect was found in nonsteroidal anti-inflammatory drugs and the objective response rate of all medications. High-level evidence suggested that using PPIs before or after the initiation of immunotherapy and using steroids during the first-course immunotherapy could weaken the OS of patients with NSCLC. Meanwhile, the negative effects of antibiotics and opioids on OS or PFS were only supported by moderate or low-level evidence. CONCLUSIONS:The concurrent usage of PPIs or steroids adversely affects the survival of patients with NSCLC receiving immunotherapy. Future investigations are required to ascertain whether these adverse effects are primarily attributed to the comorbidities or the concurrent medications.

Abstract Background: Fuzheng Kang-Ai decoction (FZKA), which consists of twelve Chinese herbal medicines (CHM), has been extensively used in the treatment of Non-Small Cell Lung Cancer (NSCLC) patients. It was reported in our preceding study that the progression-free survival (PFS) could be prolonged and the toxic effect was reduced after the combination of FZKA and Gefitinib (GFTN) comparing to GFTN alone. Recent studies have shown that FZKA could promote ferroptosis in NSCLC cells. Hence, we assumed that FZKA might strengthen the effect of GFTN by regulating cell ferroptosis in NSCLC. Results: First of all, according to our results, FZKA increased the inhibition effect of NSCLC by GFTN in vitro. Next, we found that FZKA increased the sensitivity of GFTN on cell ferroptosis by testing lipid peroxidation and intracellular-free iron. Interestingly, the effect of FZKA on increasing sensitivity of GFTN in NSCLC cells could be reversed by blocking ferroptosis. Additionally, the results demonstrated that the expression of AMPKα was increased and SLC7A11 reduced in the combined treatment group, at both mRNA and protein levels. Notably, the inhibition of AMPKα reversed the effect of FZKA on increasing GFTN sensitivity. Finally, in vivoexperiments validated that FZKA strengthened the effect of GFTN by inducing NSCLC cell ferroptosis. Conclusions: Based on our findings, we conclude that FZKA increases the sensitivity of GFTN via inducing NSCLC ferroptosis through AMPK/SLC7A11 pathway, providing the solid evidences to the treatment of FZKA together with GFTN in NSCLC patients.

Lung cancer is the leading cause of cancer-related deaths worldwide. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) showed great therapeutic efficacy for non-small cell lung cancer (NSCLC) patients. However, acquired resistance severely limits the clinical application and efficacy of EGFR-TKIs. In the current study, we found that solamargine (SM), a natural alkaloid derived from the fruit of Lycium tomato lobelia, has been found to inhibit the progression of NSCLC and enhance the anticancer effect of EGFR-TKIs. In brief, SM significantly inhibited the cell viability of NSCLC cells and enhanced the anticancer effect of gefitinib (GFTN) and erlotinib (ERL). Mechanistically, SM decreased the expression of MALAT1 and induced miR-141-3p, whereas reduced SP1 protein levels. Interestingly, both MALAT1 and Sp1 have classical and conservative binding sites of miR-141-3p in their 3'-UTR regions. Silence of MALAT1 and overexpression of miR-141-3p both decreased the protein expression of Sp1. Subsequently, promoter activity and protein expression of IGFBP1 were upregulated by SM, which was not observed in cells with SP1 overexpression. Moreover, the inhibitory effect of SM on cell growth was significantly blocked by knockdown of IGFBP1 expression. More importantly, the combination of SM and GFTN synergistically inhibited the progression of lung cancer. Similar results were observed in experiments in vivo. Finally, the clinical relevance of MALAT1, Sp1 and IGFBP1 was further validated using bioinformatics analysis. Taken together, we confirmed that SM significantly enhanced the anticancer effect of EGFR-TKIs by regulating the MALAT1/miR-141-3p/Sp1/IGFBP1 signaling pathway. This study unravels a novel mechanism and suggests a new potential NSCLC-associated therapy.

Background: Current treatments for lung cancer have their own deficiencies, such as severe adverse effect. Therefore, more safe and effective drugs are needed. Purpose: Fuzheng Kang-Ai (FZKA for short) has been applied as an adjuvant treatment in advanced Non-Small Cell Lung Cancer (NSCLC) patients for decades in China, showing a definitive effect with minimal toxicities. However, the underlying mechanism is yet to be identified. Study design: Both in vitro and in vivo experiments were performed in this study to identify the exact mechanism by which FZKA inhibits NSCLC cell proliferation. Methods: MTT and CCK-8 assays were used to detect cell viability. Xenograft model was performed for in vivo experiments. CircRNA and miRNA sequencing were used to find the differentially expressed circRNAs and miRNAs, respectively. qRT-PCR was performed to check the expression levels of circRNA, miRNA and mRNA. BaseScope was carried out to observe the expression of circRNA in situ. Actinomycin D and RNase R experiments were done to show the stability of circRNA. Nuclear-cytoplasmic fractionation and FISH were used to identify the localization of circRNA and miRNA. Pull-down, RIP, and luciferase activity assays were performed to show the biding ability of circRNA, miRNA and target proteins. Flow cytometry was done to observe cell apoptosis. Western blot and IHC were done to detect the protein expression. TCGA database was used to analyze the survival rate. Results: FZKA inhibits NSCLC cell proliferation both in vitro and in vivo. Hsa_circ_0048091 and hsa-miR-378g were the most differentially expressed circRNA and miRNA, respectively, after FZKA treatment. Silencing hsa_circ_0048091 and overexpressing hsa-miR-378g promoted cell proliferation and reversed the inhibition effect of FZKA on NSCLC, respectively. Hsa-miR-378g was sponged by hsa_circ_0048091, and the overexpression of miR378g reversed the inhibition effect of hsa_ circ_0048091 on NSCLC. ARRDC3, as a target of hsa-miR-378g, was increased by FZKA treatment. Silencing ARRDC3 reversed both the inhibition effect of FZKA and miR-378g inhibitor on NSCLC. Conclusion: This study, for the first time, has established the function of hsa_circ_0048091, hsa- miR-378g, and ARRDC3 in lung cancer. It also shows that FZKA inhibits NSCLC cell proliferation through hsa_circ_0048091/hsamiR-378g/ARRDC3 pathway, uncovering a novel mechanism by which FZKA controls human NSCLC cell growth.

BACKGROUND:Kaempferol is extracted from Hedyotis diffusa, exerting an obvious anti-cancer effect. Here in the present study, we explored the anti-cancer effects and mechanism of kaempferol in non-small cell lung cancer cell (NSCLC).PURPOSE:Our objective is to figure out the molecular mechanism by which kaempferol promotes autophagy in NSCLC cells.STUDY DESIGN:A549 and H1299 NSCLC cell lines were used for in vitro experiments. And BALB/c nude mice of NSCLC were used to perform in vivo experiments.METHODS:For in vitro experiments, CCK-8 and EdU assay was used to observe the effect of kaempferol on NSCLC cell proliferation. Confocal microscopy of mCherry-EGFR-LC3 assay and electron microscopy assay were used to detect NSCLC cell autophagy. Protein expression was determined using Western blot, and mRNA expression was determined using qRT-PCR. Flow cytometry was performed to detect the cell apoptosis. For in vivo experiments, a subcutaneously implanted tumor model in BALB/C nude mice was performed using human NSCLC cell line A549-Luc. The kaempferol effect on NSCLC mice model was detected by measuring the tumor weight and bioluminescence intensity. Immunohistochemistry was done to measure the key protein expression from mice tumor tissues.RESULTS:Our results confirmed that kaempferol inhibited NSCLC cell proliferation significantly. And it promoted NSCLC cell autophagy, leading to NSCLC cell death. Interestingly, Met-was greatly inhibited at both protein and mRNA levels. Meanwhile, PI3K/AKT/mTOR signaling pathway was inhibited accordingly. Furthermore, overexpressing Met-reversed the effect of kaempferol on NSCLC cell viability and cell autophagy with significance. Finally, the above effect and pathway were validated using the xenograft model.CONCLUSION:Kaempferol may exert its anti-NSCLC effect by promoting NSCLC cell autophagy. Mechanistically, Met-and its downstream PI3K/AKT/mTOR signaling pathway were involved in the process, which provides a novel mechanism how kaempferol functions in inhibiting NSCLC.

Background: While laparoscopic adrenalectomy (LA) represents a gold standard for treating most adrenal lesions, no effective visual model for the prediction of perioperative complications of retroperitoneal laparoscopic adrenalectomy (RLA) exists.Methods: A retrospectively study was conducted involving all consecutive patients underwent unilateral RLA for adrenal disease from January 2012 to December 2021. The entire cohort was randomly divided into 2 subsets (70% of the data for training, 30% for validation). Subsequently, a Least Absolute Shrinkage Selection Operator (LASSO) regression was performed to select the predictor variables, which were further consolidated via random forest (RF) and Boruta algorithm. Then the nomogram was established using the bivariate logistic regression analysis. Eventually, the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were employed to evaluate discrimination, calibration and clinical usefulness of the model, respectively.Results: A total of 610 patients underwent unilateral RLA for adrenal diseases were enrolled. After machine learning analyses, a weighted nomogram was established with 7 factors associated with complications including operative time, lesion laterality, intraoperative blood loss, pheochromocytoma, body mass index (BMI) and 2 preoperative comorbidities (respiratory diseases, cardiovascular diseases (CVD)). The model displayed a fine calibration curve for perioperative complications evaluation in both the training dataset (P=0.847) and validation dataset (P=0.248). ROC with AUC revealed an excellent discrimination in the training dataset (0.817, 95% CI: 0.758-0.875) and validation dataset (0.794, 95% CI: 0.686-0.901). DCA curves showed that using this nomogram provided a more net benefit where threshold probabilities lay in the range of 0.1 to 0.9.Conclusions: An effective nomogram that incorporating 7 predictors was established in this study to identify patients at high risk of perioperative complications for RLA. It would contribute to the improvement of perioperative strategy due to its accuracy and convenience.

The study aimed to investigate the anti-tumor effects and underlying mechanisms of Enzalutamide (ENZ) and Arsenic trioxide (ATO) co-treatment on castration-resistant prostate cancer (CRPC). The effects on C4-2B cells were initially evaluated by colony formation assay, FACS analysis, and DNA fragmentation detection. Bioinformatics methods including mRNA-sequencing and gene enrichment analysis were used to screen the underlying target genes and pathways related to their actions. Western blot was employed to assess the expression levels of protein-related angiogenesis, apoptosis, DNA repair, and the screened genes. Finally, the effects were further verified in subcutaneous tumor models and tissue sections from the xenografts. It was found that not only could ENZ combination with ATO significantly inhibit cell proliferation and angiogenesis, but also induce cell arrest and apoptosis in C4-2B cells. In addition, interruption of the DNA damage repair-related pathways also occurred as a result of their combined effects. Western blot analysis further suggested that proteins involved in these pathways, especially P-ATR and P-CHEK1 were significantly reduced. In addition, their combination also inhibited the tumor growth of xenografts. Altogether, ENZ combination with ATO synergistically improved the therapeutic effects and suppressed CRPC progression through regulation of the ATR-CHEK1-CDC25C pathway.

癌性发热是晚期恶性肿瘤的常见合并症.吴万垠教授认为癌性发热的根本病因是癌毒内伏,病位在里或半表半里,发病阶段属于温病的气、营、血分,采用经方治疗收到较好的疗效.本文对吴万垠教授用经方治疗癌性发热的经验进行阐述,并附医案,以供临床参考.

Background: In China, Brucea javanica oil emulsion injection (BJOEI) has been used as adjuvant therapy to treat cancer for many years. Many systematic reviews (SRs) or meta-analyses (MAs) were published to evaluate its efficacy and safety. Nevertheless, uneven quality made it difficult to reach a consensus and there has been no specific review to integrate the evidence of BJOEI for cancer at present. Therefore, a comprehensive evidence map is needed to guide clinicians. Purpose: We, for the first time, conducted an overview to assess the SRs/MAs of BJOEI, and provided a comprehensive evidence map to guide clinicians. Besides, this study provided a promising direction for future research to promote the generation of advanced evidence. Study design: An overview of SRs or MAs. Methods: The pre-defined search strategies were applied to 8 databases. Suitable SRs/MAs were included according to the inclusion and exclusion criteria. Methodological quality, reporting quality, and risk of bias were assessed. An evidence map was conducted to show the situation of clinical evidence. Results: 27 SRs/MAs in 7 cancer types were included in this overview. The main problems of SRs/MAs were concentrated on the following aspects: without registration or protocol, lacking gray literature retrieval and a list of excluded studies, incomplete description in the literature retrieval strategy or the methods of merging results, the bias of each synthetic result, less exploration in heterogeneity or publication bias, deficiencies in assessing evidence quality and less description in conflict, funding or access to relevant information. Based on the rules of GRADE, the evidence quality of 154 items in 27 SRs/MAs was defined as moderate quality (103 items), low quality (44 items), and very low-quality (7 items). Especially, risk of bias (154 items), imprecision (27 items), inconsistency (20 items), and publication bias (9 items) were the main downgrading factors. Conclusion: BJOEI may be a promising adjuvant therapy for treating cancer, especially in the digestive system. However, high-quality SRs/MAs are expected to be carried out to improve the reliability of the above conclusion in the future.

肿瘤免疫编辑假说认为免疫系统在肿瘤发生发展过程中具有双重作用,分为免疫清除、免疫平衡以及免疫逃逸三个序贯的阶段.中医理论认为阴阳失衡是导致肿瘤发生发展的关键.中医药治疗肿瘤强调通过调整阴阳达到阴平阳秘的平衡状态,从而实现控制肿瘤生长、改善患者临床症状、提高患者生活质量等目的.本文应用肿瘤免疫编辑假说,将机体阴阳平衡与机体免疫清除、阴阳失衡与肿瘤细胞免疫逃逸联系起来,并结合目前中医药治疗肿瘤实践,尝试探讨中医基本病机中的"阴阳平衡"与肿瘤免疫编辑假说间的相关性,以为肿瘤免疫治疗中充分发挥中医药多靶点、多层次、多因素的作用提供借鉴.