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Rong Huang,1,&ast; Rui Zheng,2,&ast; Shui Fu,1 Zuo Jie Li3 1Clinical Laboratory Department, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Central Laboratory, Taizhou Hospital of Zhejiang Province, Taizhou, People’s Republic of China; 3Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, Wenzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuo Jie Li, Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, No. 2288 Yucang Road, Cangnan County, Wenzhou, Zhejiang Province, 325800, People’s Republic of China, Tel +86 577-64810162, Email 15088908102@163.comObjective: Pertussis is a highly contagious respiratory disease, and early diagnosis and timely treatment are crucial for reducing complications and transmission. In this study, we analyzed the prevalence of pertussis and assessed the value of the WBC and lymphocyte percentage in its screening.Methods: A retrospective analysis was conducted on global pertussis data from the past decade. Patients who recently underwent pertussis nucleic acid detection and complete blood count (CBC) in our hospital were selected. Based on the results, 538 patients were classified into the pertussis group, and 595 into the control group. White blood count (WBC) and lymphocyte percentages were compared, diagnostic efficacy was calculated, and evaluate their application value in the diagnosis of pertussis.Results: In the past decade, the global incidence of pertussis first decreased, then increased. In China and Zhejiang province, it fluctuated but showed an upward trend recently. In Zhejiang Province, pertussis was more prevalent in summer and winter and rose last year. Between 2018 and 2020, most pertussis cases in China were infants under 1 year old. Last year, only 1.12% of patients in our hospital were infants, with more patients over 5 years old. WBC, lymphocyte percentage, and platelet count (PLT) was higher in the pertussis group (P < 0.05). Logistic regression showed that WBC, lymphocyte percentage, and PLT were correlated with pertussis infection. Sequential analysis showed that the WBC, lymphocyte percentage, and Youden’s index for both combined were 0.124, 0.082, and 0.044, respectively.Conclusion: The global incidence of pertussis is rising, with significant increases among adolescents and adults. Improved prevention and control strategies are needed. WBC and lymphocyte percentage serve as auxiliary diagnostic indicators, but their efficacy is limited.Keywords: pertussis, epidemiology, WBC, lymphocyte percentage, diagnostic competence

Changhong Xu,1,&ast; Yun Deng,1,&ast; Xinyi Gong,2,&ast; Huabin Wang,1 Jiangwei Man,1 Hailong Wang,1 Kun Cheng,1 Huiming Gui,1 Shengjun Fu,1 Shenghu Wei,3 Xiaoling Zheng,4 Tuanjie Che,4 Liyun Ding,3 Li Yang1 1Department of Urology, Institute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China; 2The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, 730030, People’s Republic of China; 3School of Physical Science and Technology, Lanzhou University, Lanzhou, 730000, People’s Republic of China; 4Innovation Center of Functional Genomics and Molecular Diagnostics Technology of Gansu Province, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang; Liyun Ding, Email ery_yangli@lzu.edu.cn; dingly@lzu.edu.cnBackground: Renal ischemia-reperfusion injury (RIRI) is a significant cause of acute kidney injury, complicating clinical interventions such as kidney transplants and partial nephrectomy. Recent research has indicated the role of cuproptosis, a copper-dependent cell death pathway, in various pathologies, but its specific involvement in RIRI remains insufficiently understood. This study aims to investigate the role of cuproptosis-related genes in RIRI and establish robust diagnostic models.Methods: We analyzed transcriptomic data from 203 RIRI and 188 control samples using bioinformatics tools to identify cuproptosis-related differentially expressed genes (CRDEGs). The relationship between CRDEGs and immune cells was explored using immune infiltration analysis and correlation analysis. Gene Set Enrichment Analysis (GSEA) was conducted to identify pathways associated with CRDEGs. Machine learning models, including Least Absolute Shrinkage and Selection Operator(LASSO) logistic regression, Support Vector Machine Recursive Feature Elimination (SVM-RFE), Clustering analysis, and weighted gene co-expression network analysis (WGCNA), were used to construct diagnostic gene models. The models were validated using independent datasets. Experimental validation was conducted in vivo using a mouse bilateral RIRI model and in vitro using an HK-2 cell hypoxia-reoxygenation (HR) model with copper chelation intervention. HE, PAS, and TUNEL staining, along with plasma creatinine and blood urea nitrogen (BUN) measurements, were used to evaluate the protective effect of the copper chelator D-Penicillamine (D-PCA) on RIRI in mice. JC-1 and TUNEL staining were employed to assess apoptosis in HK-2 cells under hypoxia-reoxygenation conditions. Immunofluorescence and Western blot (WB) techniques were used to verify the expression levels of the SDHB and NDUFB6 genes.Results: A total of 18 CRDEGs were identified, many of which were significantly correlated with immune cell infiltration. GSEA revealed that these genes were involved in pathways related to oxidative phosphorylation and immune response regulation. Four key cuproptosis marker genes (LIPA, LIPT1, SDHB, and NDUFB6) were incorporated into a Cuproptosis Marker Gene Model(CMGM), achieving an area under the curve (AUC) of 0.741– 0.834 in validation datasets. In addition, a five-hub-gene SVM model (MOAP1, PPP2CA, SYL2, ZZZ3, and SFRS2) was developed, demonstrating promising diagnostic performance. Clustering analysis revealed two RIRI subtypes (C1 and C2) with distinct molecular profiles and pathway activities, particularly in oxidative phosphorylation and immune responses. Experimental results showed that copper chelation alleviated renal damage and cuproptosis in both in vivo and in vitro models.Conclusion: Our study reveals that cuproptosis-related genes are significantly involved in RIRI, particularly influencing mitochondrial dysfunction and immune responses. The diagnostic models developed showed promising predictive performance across independent datasets. Copper chelation demonstrated potential therapeutic effects, suggesting that cuproptosis regulation may be a viable therapeutic strategy for RIRI. This work provides a foundation for further exploration of copper metabolism in renal injury contexts.Keywords: cuproptosis, renal ischemia-reperfusion injury, RIRI, gene diagnostic models, copper chelators, bioinformatics analysis

Yihua Jin,1,&ast; Zhimin Geng,1,2,&ast; Kun Lin,1 Xinyu Gu,1 Xiwei Feng,1 Songling Fu,1 Wei Wang,1 Chunhong Xie,1 Yujia Wang,1 Fangqi Gong1 1Department of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 2Pediatric Cardiovascular Diseases Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fangqi Gong; Yujia Wang, Email gongfangqi@zju.edu.cn; wangyujia@zju.edu.cnPurpose: Kawasaki disease (KD) is an acute systemic vasculitis that is associated with dysregulated immune responses. Monocytes play a central role in innate immunity. Our previous single-cell RNA sequencing of peripheral blood mononuclear cells (PBMC) revealed a new subset of monocytes in children with KD called L-Selectin+ classical monocytes (SELL+ CM). Therefore, we aimed to investigate the correlation between KD and SELL+ CM.Patients and Methods: Peripheral blood samples were collected from 81 KD patients, 18 febrile patients and 36 healthy children before treatment. Among them, ten KD patients were followed up, and samples were obtained before and after intravenous immunoglobulin (IVIG) treatment. Analysis of SELL+ CM was performed using flow cytometry. Additionally, ROC curve analysis was conducted to assess the diagnostic value of SELL+ CM for KD.Results: Classical monocytes (CM) expressed the highest levels of L-selectin in children with KD. The ratio of SELL+ CM in CM was significantly higher in KD patients than in febrile and healthy children. Following IVIG treatment, the ratio of SELL+ CM in CM showed a downward trend. The receiver operating characteristic (ROC) curve analysis (the area under the curve, AUC = 0.71) indicated the potential diagnostic value of SELL+ CM in KD. The correlation analysis suggested that SELL+ CM may serve as a new clinical index for patients with KD.Conclusion: In KD, the ratio of SELL+ CM in CM significantly increases during the acute phase, which may become a potential biomarker and help facilitate KD diagnosis based on clinical features.Keywords: Kawasaki disease, monocyte subsets, L-Selectin, coronary artery lesions

Wenlu Li,1,2,&ast; Yaolin Gong,1,2,&ast; Jing Zhang,1,2 Jiong Liu,1,2 Jiali Li,1,2 Shaozhi Fu,3 Wen Xiu Ren,1,2 Jian Shu1,2 1Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Xiu Ren; Jian Shu, Department of Radiology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of China, Email xrenwenxiux@swmu.edu.cn; shujiannc@swmu.edu.cnIntroduction: Targeting, imaging, and treating tumors represent major clinical challenges. Developing effective theranostic agents to address these issues is an urgent need.Methods: We introduce an “all-in-one” tumor-targeted theranostic platform using CuFeSe2-based composite nanoparticles (CuFeSe2@PA) for magnetic resonance (MR) and computed tomography (CT) dual model imaging-guided hyperthermia tumor ablation. Plerixafor (AMD3100) is bonded to the surface of CuFeSe2 as a targeting unit. Due to the robust interaction between AMD3100 and the overexpressed Chemokine CXC type receptor 4 (CXCR4) on the membrane of 4T1 cancer cells, CuFeSe2@PA specifically recognizes 4T1 cancer cells, enriching the tumor region.Results: CuFeSe2@PA serves as a contrast agent for T2-weighted MR imaging (relaxivity value of 1.61 mM− 1 s− 1) and CT imaging. Moreover, it effectively suppresses tumor growth through photothermal therapy (PTT) owing to its high photothermal conversion capability and stability, with minimized side effects demonstrated both in vitro and in vivo.Discussion: CuFeSe2@PA nanoparticles show potential as dual-mode imaging contrast agents for MR and CT and provide an effective means of tumor treatment through photothermal therapy. The surface modification with Plerixafor enhances the targeting ability of the nanoparticles, performing more significant efficacy and biocompatibility in the 4T1 cancer cell model. The study demonstrates that CuFeSe2@PA is a promising multifunctional theranostic platform with clinical application potential. Keywords: tumor targeting, photothermal therapy, dual model imaging, theranostic platform, chemokine cxc type receptor 4

Roumei Wang,1,&ast; Shien Fu,2,&ast; Rui Huang,3,&ast; Chengcheng Qiu,1 Yunxia Tang,1 Yaoli Liu1 1Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3College of Public Hygiene of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaoli Liu, Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-771-5356706, Email 100youngly@163.comObjective: This study aimed to evaluate the quadriceps femoris in patients with chronic thyrotoxic myopathy (CTM) using musculoskeletal ultrasound and to explore its practical clinical value for the diagnosis of CTM.Methods: A total of 241 subjects recruited from the First Affiliated Hospital of Guangxi Medical University were surveyed for detailed medical history and underwent grip strength tests, fixed-distance walking, and quadriceps femoris ultrasound examinations. Differences in muscle parameters between the CTM, non-CTM, and healthy groups were analyzed. An Receiver operating characteristic (ROC) curve was established to analyze the predictive value of various ultrasound measurements for CTM, and Spearman correlation analysis and binary logistic regression were applied to explore the factors associated CTM.Results: The quadriceps femoris contraction index, muscle thickness, muscle cross-sectional area, and pennation angle in the CTM group were significantly lower than those in the non-CTM and healthy groups (p< 0.01). The ROC curve prediction showed that the pennation angle had the best sensitivity and specificity for diagnosing myogenesis, with an area under the curve of 89%. Moreover, the pennation angle of the CTM group was positively correlated with step speed (r=0.245, p=0.031) and body surface area (r=0.276, p=0.014), but negatively correlated with age (r=− 0.306, p=0.007). Regression analysis showed that the quadriceps femoris contraction index, muscle thickness, pennation angle, and cross-sectional area were factors that related the CTM. After adjusting for potential confounding factors, the association between Muscle Bundle Length and CTM became significant (OR=1.99, 95% CI: 1.22, 3.35, p=0.007). Muscular echo in patients was observed to varying degrees of enhancement.Conclusion: Musculoskeletal ultrasonography in the quantitative analysis of muscle parameters and muscle echo of the quadriceps femoris can provide essential imaging evidence for predicting CTM.Keywords: chronic thyrotoxic myopathy, musculoskeletal ultrasound, muscle echo intensity, Heckmatt Scale

Tao Chen,1– 3,&ast; Yumeng Wei,1– 3,&ast; Suyu Yin,1– 3,&ast; Wen Li,1– 3 Yuxiang Wang,1– 3 Chao Pi,1– 3 Mingtang Zeng,3,4 Xiaodong Wang,5 Ligang Chen,6 Furong Liu,7 Shaozhi Fu,8 Ling Zhao2,3 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University; Luzhou, Sichuan, 646000, People’s Republic of China; 3Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 4Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 5Department of Hepatobiliary Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 6Department of neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 7Department of Oncology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 8Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaozhi Fu, Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86 830-3165698, Fax +86 830-3165690, Email shaozhifu513@163.com Ling Zhao, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, China, Tel +86 830 2681630, Email zhaoling@swmu.edu.cnPurpose: The present study aimed to develop a lipid nanoplatform, denoted as “BAL-PTX-LN”, co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs.Methods: BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining.Results: BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 μg/mL vs 31.722 μg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration.Conclusion: BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications. Keywords: baicalin derivative, paclitaxel, chemotherapy, lung cancer, lipid nano platform, combination therapy

CUPID is a next-generation bolometric experiment aiming at searching for neutrinoless double-beta decay with ∼250 kg of isotopic mass of 100Mo. It will operate at ∼10 mK in a cryostat currently hosting a similar-scale bolometric array for the CUORE experiment at the Gran Sasso National Laboratory (Italy). CUPID will be based on large-volume scintillating bolometers consisting of 100Mo-enriched Li2MoO4 crystals, facing thin Ge-wafer-based bolometric light detectors. In the CUPID design, the detector structure is novel and needs to be validated. In particular, the CUORE cryostat presents a high level of mechanical vibrations due to the use of pulse tubes and the effect of vibrations on the detector performance must be investigated. In this paper we report the first test of the CUPID-design bolometric light detectors with NTD-Ge sensors in a dilution refrigerator equipped with a pulse tube in an above-ground lab. Light detectors are characterized in terms of sensitivity, energy resolution, pulse time constants, and noise power spectrum. Despite the challenging noisy environment due to pulse-tube-induced vibrations, we demonstrate that all the four tested light detectors comply with the CUPID goal in terms of intrinsic energy resolution of 100 eV RMS baseline noise. Indeed, we have measured 70-90 eV RMS for the four devices, which show an excellent reproducibility. We have also obtained high energy resolutions at the 356 keV line from a 133Ba source, as good as Ge semiconductor γ detectors in this energy range.

An array of twelve 0.28 kg lithium molybdate (LMO) low-temperature bolometers equipped with 16 bolometric Ge light detectors, aiming at optimization of detector structure for CROSS and CUPID double-beta decay experiments, was constructed and tested in a low-background pulse-tube-based cryostat at the Canfranc underground laboratory in Spain. Performance of the scintillating bolometers was studied depending on the size of phonon NTD-Ge sensors glued to both LMO and Ge absorbers, shape of the Ge light detectors (circular vs. square, from two suppliers), in different light collection conditions (with and without reflector, with aluminum coated LMO crystal surface). The scintillating bolometer array was operated over 8 months in the low-background conditions that allowed to probe a very low, μBq/kg, level of the LMO crystals radioactive contamination by 228Th and 226Ra.

CUPID is a next-generation tonne-scale bolometric neutrinoless double beta decay experiment that will probe the Majorana nature of neutrinos and discover lepton number violation in case of observation of this singular process. CUPID will be built on experience, expertise and lessons learned in CUORE and will be installed in the current CUORE infra-structure in the Gran Sasso underground laboratory. The CUPID detector technology, successfully tested in the CUPID-Mo experiment, is based on scintillating bolometers of Li2MoO4 enriched in the isotope of interest 100Mo. In order to achieve its ambitious science goals, the CUPID collaboration aims to reduce the backgrounds in the region of interest by a factor 100 with respect to CUORE. This performance will be achieved by introducing the high efficient α/β discrimination demonstrated by the CUPID-0 and CUPID-Mo experiments, and using a high transition energy double beta decay nucleus such as 100Mo to minimize the impact of the gamma background. CUPID will consist of about 1500 hybrid heat-light detectors for a total isotope mass of 250 kg. The CUPID scientific reach is supported by a detailed and safe background model based on CUORE, CUPID-Mo and CUPID-0 results. The required performances have already been demonstrated and will be presented.

Dan Lv,1 Yuling Liu,1 Ruying Tang,1 Sai Fu,1 Shasha Kong,1 Qian Liao,1 Hui Li,1,2 Longfei Lin1 1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China; 2Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Hui Li; Longfei Lin, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Nanxiaojie 16, 8 Dongzhimennei Ave, Beijing, 100700, People’s Republic of China, Tel +86-10-64032658, Email hli1967@icmm.ac; lflin@icmm.ac.cnAbstract: The potential anti-cancer effect of traditional Chinese medicine (TCM) monomers has been widely studied due to their advantages of well-defined structure, clear therapeutic effects, and easy quality control during the manufacturing process. However, clinical trial information on these monomers is scarce, resulting in a lack of knowledge regarding the research progress, efficacy, and adverse reactions at the clinical stage. Therefore, this study systematically reviewed the clinical trials on the anti-cancer effect of TCM monomers registered in the Clinicaltrials.gov website before 2023.4.30, paying special attention to the trials on tumors, aiming to explore the research results and development prospects in this field. A total of 1982 trials were started using 69 of the 131 TCM monomers. The number of clinical trials performed each year showed an overall upward trend. However, only 26 monomers entered into 519 interventional anti-tumor trials, with vinblastine (194, 37.38%) and camptothecin (146, 28.13%) being the most used. A total of 45 tumors were studied in these 519 trials, with lymphoma (112, 21.58%) being the most frequently studied. Clinical trials are also unevenly distributed across locations and sponsors/collaborators. The location and the sponsor/collaborator with the highest number of performed trials were the United States (651,32.85%) and NIH (77). Therefore, China and its institutions still have large room for progress in promoting TCM monomers in anti-tumor clinical trials. In the next step, priority should be given to the improvement of the research and development ability of domestic enterprises, universities and other institutions, using modern scientific and technological means to solve the problems of poor water solubility and strong toxic and side effects of monomers, so as to promote the clinical research of TCM monomers.Keywords: traditional Chinese medicine monomers, anti-cancer, interventional clinical trials, research progress, adverse reactions

Weijian Zhu,1 Ying He,1 Mufang Huang,1 Shezhu Fu,1 Ziyi Liu,1 Xiaoqi Wang,1 Zhixin Li,1 Xiaoliang Li,1 Jiangming Chen,2 Yangqiu Li3 1Department of Hematology, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital), Zhuahai, 519050, People’s Republic of China; 2Department of Haematology, Wuzhou Gongren Hospital, Wuzhou, 543001, People’s Republic of China; 3Institute of Hematology, School of Medicine, Jinan University, Guangzhou, 10632, People’s Republic of ChinaCorrespondence: Yangqiu Li, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, 510632, People’s Republic of China, Email yangqiuli@hotmail.comObjective: We evaluated the long-term safety and efficacy of thalidomide in the treatment of transfusion-dependent β-thalassemia (TDT).Methods: Fifty patients with TDT were treated with thalidomide and followed-up for 5 years. Thalidomide at a 50 mg dose was administered once a day after dinner. The dose was increased to 150 mg/d after 3 d if well tolerated. After 1 year of treatment, the hemoglobin (Hb) level was stabilized at its maximum, and thalidomide was gradually reduced and maintained at the minimum dose. The hematological response, transfusion dependence, and haemolytic indicators were assessed.Results: At 9 month of follow-up, 38 (76%) patients achieved an excellent response, 1 (2%) a good response, 4(8%) a minor response, and 7(14%) did not show a response. The overall response rate was 86%. At 9 months, the Hb level increased from 79.0 ± 13.2 g/L at baseline to 99.0 ± 13.7g/L (P< 0.001). Patients who achieved excellent response continued to show an increase in Hb levels during follow-up. At 48 months, the mean Hb level was 98.99 ± 10.3g/L; 21 patients (84.0%) became transfusion independent. Thalidomide was reduced and maintained to 25 mg/d in three of these patients. Moreover, five patients completed 60 months of follow-up, and with a mean Hb level of 99.8 ± 6.7g/L. During follow-up, grade 1– 2 adverse drug reactions were noted; however, no grade 3 or higher adverse event was reported. However, no decrease in hemolytic indicators was observed.Conclusion: Thalidomide was well tolerated in the long term, while it significantly improved Hb levels and reduced the transfusion burden.Keywords: β-thalassemia, transfusion-dependent, thalassemia, thalidomide, foetal hemoglobin

Canhao Lai,1,&ast; Ruichen Li,1,&ast; Weili Tang,1 Jinyu Liu,1 Xinfang DXF Duan,1 Dingsu Bao,1,2 Huan Liu,1 Shijie Fu1 1Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China; 2Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shijie Fu; Huan Liu, Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 13882759783, Email fushijieggj@126.com; 20016040@163.comAbstract: Metabolic syndrome (MS) is a multifaceted pathological condition characterized by the atypical accumulation of various metabolic components such as central obesity or excess weight, hyperlipidemia, low-density lipoprotein (LDL), hypertension, and insulin resistance. Recently, MS has been recognized as a notable contributor to heart and circulatory diseases. In addition, with increasing research, the impact of MS on tendon repair and disease has gradually emerged. Recent studies have investigated the relationship between tendon healing and diseases such as diabetes, dyslipidemia, obesity, and other metabolic disorders. However, diabetes mellitus (DM), hypercholesterolemia, obesity, and various metabolic disorders often coexist and together constitute MS. At present, insulin resistance is considered the major pathological mechanism underlying MS, central obesity is regarded as the predominant factor responsible for it, and dyslipidemia and other metabolic diseases are known as secondary contributors to MS. This review aims to evaluate the current literature regarding the impact of various pathological conditions in MS on tendon recovery and illness, and to present a comprehensive overview of the effects of MS on tendon recovery and diseases, along with the accompanying molecular mechanisms.Keywords: metabolic syndrome, tendon, diabetes mellitus, hyperlipidemia, obesity, hypertension

CUORE Upgrade with Particle IDentification (CUPID) is a foreseen ton-scale array of Li2MoO4 (LMO) cryogenic calorimeters with double readout of heat and light signals. Its scientific goal is to fully explore the inverted hierarchy of neutrino masses in the search for neutrinoless double beta decay of 100Mo. Pile-up of standard double beta decay of the candidate isotope is a relevant background. We generate pile-up heat events via injection of Joule heater pulses with a programmable waveform generator in a small array of LMO crystals operated underground in the Laboratori Nazionali del Gran Sasso, Italy. This allows to label pile-up pulses and control both time difference and underlying amplitudes of individual heat pulses in the data. We present the performance of supervised learning classifiers on data and the attained pile-up rejection efficiency.

Tianrui Zhang,1,&ast; Sha Fu,1,&ast; Xiaofeng Cao,2 Yangjingyi Xia,1 Manyan Hu,1 Qinghua Feng,1 Yujun Cong,1 Yuan Zhu,1 Xiaogang Tang,1 Minghua Wu1 1Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Neurology, Jiangyan Hospital of Chinese Medicine, Taizhou, Jiangsu, 225500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minghua Wu; Xiaogang Tang, Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of China, Tel +8613951786719, Email yfy0069@njucm.edu.cn; zhongyiTXG@163.comPurpose: According to many previous studies, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and hypersensitive C-reactive protein (CRP) are commonly used as important indicators to assess the prognosis of intravenous thrombolysis in AIS patients. Based on this, we used two novel biomarkers C-NLR (CRP/neutrophil-to-lymphocyte ratio) and C-LMR (CRP×lymphocyte-to-monocyte ratio) to investigate their correlation with 90-day outcomes in AIS patients after intravenous thrombolysis.Patients and Methods: A total of 204 AIS patients who received intravenous thrombolysis at the Stroke Center of Jiangsu Province Hospital of Chinese Medicine from January 2021 to December 2022 were retrospectively included. All patients were followed up 90 days after thrombolysis to assess their prognosis. Patients with a modified Rankin scale score (mRS) of 3– 6 were included in the unfavorable outcome group, and those with a score of 0– 2 were included in the favorable outcome group. Logistic regression analysis, receiver operating characteristic (ROC) curve, and Kaplan–Meier survival curve were used to investigate the association between C-NLR, C-LMR, and 90-day prognosis in AIS patients treated with early intravenous thrombolysis.Results: C-NLR (OR=1.586, 95% CI=1.098~2.291, P=0.014) and C-LMR (OR=1.099, 95% CI=1.025~1.179, P=0.008) were independent risk factors for 90-day prognosis of AIS patients treated with early intravenous thrombolysis. The higher C-NLR and C-LMR were associated with unfavorable prognosis.Conclusion: C-NLR and C-LMR can be used as biomarkers to predict prognosis of AIS patients treated with early intravenous thrombolysis.Keywords: modified rankin scale, reperfusion therapy, inflammatory reaction, cerebral vascular disease, clinical prognosis

Xiaoyu Lv,1 Hui Wang,1 Chongyang Chen,1 Yangting Zhao,1 Kai Li,1 Yawen Wang,1 Liting Wang,1,2 Songbo Fu,1,2 Jingfang Liu1,2 1The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Jingfang Liu, Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of China, Tel +86 0931-8356242, Email ljf824168@126.comAim: To explore the effects of Tirzepatide (TZP), a new hypoglycemic drug, on weight, blood lipids and blood pressure in overweight/obese patients with type 2 diabetes mellitus (T2DM).Methods: Relevant studies investigating the influence of TZP therapy on weight, lipid profiles and blood pressure in overweight/obese T2DM patients were selected from the PubMed, Embase, Web of Science and Cochrane databases from establishment until November 2022. A systematic review and meta-analysis were conducted to evaluate the effect of TZP on weight, blood lipids and blood pressure in overweight/obese patients with T2DM.Results: Eight randomized controlled trials (RCTs), comprising 7491 patients with T2DM, were included in the meta-analysis. Results showed that compared with the glucagon-like peptide-1 receptor agonist (GLP-1RA), insulin, and placebo groups, body weight, triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) levels were significantly decreased in the TZP-treated groups, while high-density lipoprotein cholesterol (HDL-C) levels increased. With the gradual increase of TZP doses, the proportions of T2DM patients with weight loss > 5% gradually increased. The 10 mg and 15 mg TZP doses had a stronger effect on the levels of TG, VLDL-C, and HDL-C. Moreover, the reduction in SBP levels in the 15 mg TZP-treated group was more pronounced than those in the 10 mg and 5 mg TZP-treated groups [MD=− 2.07, 95% CI (− 2.52, − 1.63) and MD=− 3.14, 95% CI (− 4.42, − 1.87)]. Compared with GLP-1RA, insulin, and placebo groups, the proportions of patients with HbA1c< 7% in 10mg and 15mg TZP-treated groups were significantly higher than in the 5mg TZP-treated group [OR=1.53, 95% CI (1.25, 1.8)], OR=1.7, 95% CI (1.15, 2.50)].There was no significant difference regarding the risk of adverse reactions.Keywords: tirzepatide, T2DM, weight, lipid metabolism, meta-analysis

Yongkang Xu, Shumin Fu, Kan Liu, Ye Mao, Jianbing Wu Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Jianbing Wu, Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China, Email hhgwjb@163.comPurpose: To evaluate the clinical outcomes of lenvatinib plus PD-1 inhibitors (LP) and regorafenib (R) in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure.Methods: From June 2018 to September 2021, 68 patients from a single center who received lenvatinib combined with PD-1 inhibitors or regorafenib after sorafenib treatment failure were analyzed. The tumor response and survival outcomes were compared between the LP group and R group. Prognostic factors for OS and PFS were determined using Cox proportional hazard regression models.Results: The ORR increased in the LP group (19.5% vs 7.4%, p =0.294), and the DCR was better in the R group (73.2% vs 44.4%, p =0.017). Additionally, median PFS and OS were not significantly different between the LP group and R two groups in survival analysis (PFS: 5.3 months vs 3.0 months, p =0.633; OS: 11.8 months vs 8.0 months, p =0.699). The common adverse events (≥grade 3) were hand-foot skin reactions (13.1%). In multivariate analyses, AFP≥ 400 ng/mL and ECOG PS 2 were independent risk factors for poor prognosis.Conclusion: The LP group appeared to have a trend of greater tumor response and a higher disease control rate than the R group among patients with sorafenib-resistant HCC, although PFS and OS did not differ significantly between the two groups.Keywords: hepatocellular carcinoma, lenvatinib, PD-1 inhibitors, regorafenib, sorafenib, overall survival

CUPID will be a next generation experiment searching for the neutrinolessdouble $\beta$ decay, whose discovery would establish the Majorana nature ofthe neutrino. Based on the experience achieved with the CUORE experiment,presently taking data at LNGS, CUPID aims to reach a background freeenvironment by means of scintillating Li$_{2}$$^{100}$MoO$_4$ crystals coupledto light detectors. Indeed, the simultaneous heat and light detection allows usto reject the dominant background of $\alpha$ particles, as proven by theCUPID-0 and CUPID-Mo demonstrators. In this work we present the results of thefirst test of the CUPID baseline module. In particular, we propose a newoptimized detector structure and light sensors design to enhance theengineering and the light collection, respectively. We characterized the heatdetectors, achieving an energy resolution of (5.9 $\pm$ 0.2) keV FWHM at the$Q$-value of $^{100}$Mo (about 3034 keV). We studied the light collection ofthe baseline CUPID design with respect to an alternative configuration whichfeatures gravity-assisted light detectors' mounting. In both cases we obtainedan improvement in the light collection with respect to past measures and wevalidated the particle identification capability of the detector, which ensuresan $\alpha$ particle rejection higher than 99.9%, fully satisfying therequirements for CUPID.