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Quan-Ai Zhang,1,* Wang-Sheng Luo,2,* Ji Li,3,* Qi-Wen Zhang,1 Qin Guo,1 Jian Chen,3– 5 Zhi-Qiang Liang3 1The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Cardiology, the First Affiliated Hospital of University of South China, Hengyang, People’s Republic of China; 3Department of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Anhui Province Rural Revitalization Collaborative Technical Service Center, Huangshan University, Huangshan, People’s Republic of China; 5Department of Public Health, International College, Krirk University, Bangkok, Thailand*These authors contributed equally to this workCorrespondence: Jian Chen; Zhi-Qiang Liang, Department of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200082, People’s Republic of China, Email alexandercj@126.com; liangzhiqiang006@163.comIntroduction: Acupuncture may help treat diabetes mellitus (DM), diabetic peripheral neuropathy (DPN), and adjunct therapy for cancer, but the biological mechanisms and immune-related genes involved are unclear; this study aims to clarify these aspects.Methods: Comprehensive gene expression analysis revealed differentially expressed genes (DEGs) among DM, DPN, and control samples. Key genes from WGCNA were intersected with DEGs and acupuncture targets. Inflammatory responses, immune processes, signaling pathways, immune cell infiltration, and microRNA–gene interactions were studied. Hub immune-related genes’ dysregulation was analyzed for copy number variation and gene methylation. A pan-cancer nomogram model was created to predict survival based on various factors, linking hub genes to cancer properties.Results: Our analysis found 3,217 and 2,191 DEGs in DM/control and DPN/DM comparisons, respectively, and identified 1,830 potential acupuncture targets. We pinpointed 21 key genes in DM and 43 in DPN, involved in inflammatory responses, immune processes, CAMKK2, and cAMP signaling pathways. Distinct immune cell infiltration patterns, including M0 and M2 macrophages, neutrophils, and follicular helper T cells, were noted. Further analysis revealed microRNAs and TF genes interacting with immune hub genes in both conditions. Dysregulation of eight hub immune-related genes was linked to copy number variation and gene methylation, correlating with cancer prognosis. Co-occurrence of single nucleotide variations and oncogenic mutations was observed in these genes. The pan-cancer nomogram model showed strong prognostic capabilities, and a significant association was found between the eight genes and cancer properties like angiogenesis, EMT, and cell cycle progression.Discussion: Our findings underscore the pivotal roles of MAPK3, IL1RN, SOD2, CTSD, ESR1, SLC1A1, NPY, and CCR2 in the immune response mediated by acupuncture in the context of DM, DPN, and adjunct therapy for cancer. Keywords: acupuncture, text mining, network pharmacology, immune, diabetic peripheral neuropathy, cancer

Bi-Lan Wang,1,* Yong-mei Shen,1,3,* Qiong-wen Zhang,1,* Yu-li Li,1 Min Luo,1 Ze Liu,1,2 Yan Li,1 Zhi-yong Qian,1 Xiang Gao,1 Hua-shan Shi1,2 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, 2State Key Laboratory of Biotherapy and Department of Head and Neck Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, 3Sichuang Haoyisheng Pharmacy, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Systemic administration of chemotherapy for cancer often has toxic side effects, limiting the doses that can be used in its treatment. In this study, we developed methoxy poly(ethylene glycol)-poly(caprolactone) (MPEG-PCL) micelles loaded with curcumin and doxorubicin (Cur-Dox/MPEG-PCL) that were tolerated by recipient mice and had enhanced antitumor effects and fewer side effects. It was shown that these Cur-Dox/MPEG-PCL micelles could release curcumin and doxorubicin slowly in vitro. The long circulation time of MPEG-PCL micelles and the slow rate of release of curcumin and doxorubicin in vivo may help to maintain plasma concentrations of active drug. We also demonstrated that Cur-Dox/MPEG-PCL had improved antitumor effects both in vivo and in vitro. The mechanism by which Cur-Dox/MPEG-PCL micelles inhibit lung cancer might involve increased apoptosis of tumor cells and inhibition of tumor angiogenesis. We found advantages using Cur-Dox/MPEG-PCL micelles in the treatment of cancer, with Cur-Dox/MPEG-PCL achieving better inhibition of LL/2 lung cancer growth in vivo and in vitro. Our study indicates that Cur-Dox/MPEG-PCL micelles may be an effective treatment strategy for cancer in the future. Keywords: methoxy poly(ethylene glycol), poly(caprolactone), curcumin, doxorubicin, micelles, cancer, treatment

Hua-shan Shi1,* Xiang Gao,1,3,* Dan Li,1,* Qiong-wen Zhang,1 Yong-sheng Wang,2 Yu Zheng,1 Lu-Lu Cai,1 Ren-ming Zhong,2 Ao Rui,1 Zhi-yong Li,1 Hao Zheng,1 Xian-cheng Chen,1 Li-juan Chen,11State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China; 2State Key Laboratory of Biotherapy and Department of Thoracic Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China; 3Deparment of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, People's Republic of China*These authors contributed equally to this workAbstract: Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.Keywords: liposomes, curcumin, lung cancer