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Dan Liu, Juan Tong, Erling Chen, Li Wang, Lei Xue, Xuhan Zhang, Na Zhao, Xing Hu, Changcheng Zheng Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, People’s Republic of ChinaCorrespondence: Changcheng Zheng, Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Road No. 17, Hefei, Anhui Province, 230001, People’s Republic of China, Email zhengchch1123@ustc.edu.cnBackground: The aim of the study was to evaluate the efficacy and safety of induction and consolidation with all-trans retinoic acid (ATRA) +arsenic trioxide (ATO) +anthracyclines and maintenance with ATRA +Realgar-Indigo naturalis formula (RIF) for high-risk APL.Methods: Twenty-one patients with high-risk APL treated with ATRA+ATO+ anthracyclines for induction and consolidation and ATRA+RIF for maintenance from 2012 to 2021 were analyzed. Endpoints include morphological complete remission (CR) and complete molecular remission (CMR), early death (ED) and relapse, survival and adverse events (AEs).Results: After induction treatment, all 21 patients (100%) achieved morphological CR and 14 people (66.7%) achieved CMR. Five of the 21 patients did not undergo immunological minimal residual disease (MRD) examination after induction; however, 14 of the remaining 16 patients were MRD negative (87.5%). The median time to achieve CR and CMR was 26 days (range: 16– 44) and 40 days (range: 22– 75), respectively. The cumulative probability of achieving CR and CMR in 45 days was 100% and 76.2% (95% CI: 56.9– 91.3%), respectively. All patients achieved CMR and MRD negativity after the three courses of consolidation treatment. The median follow-up was 66 months (25– 142), with no central nervous system relapse and bone marrow morphological or molecular relapse until now, and all patients survived with 100% overall survival and 100% event-free survival. Grade 4 adverse events (AEs) were observed in 3 patients (14.3%) during the induction period including arrhythmia (n = 1), pulmonary infection (n = 1) and respiratory failure (n = 1); and the most frequent grade 3 AEs were pulmonary infection, accounting for 62.0% and 28.6%, respectively, during induction and consolidation treatment, followed by neutropenia, accounting for 42.9% and 38.1%, respectively.Conclusion: For newly diagnosed high-risk APL patients, induction and consolidation with ATRA+ATO+anthracyclines and maintenance with ATRA+RIF is a highly curative treatment approach.Keywords: high-risk acute promyelocytic leukemia, all-trans retinoic acid, arsenic trioxide, realgar–Indigo naturalis formula, anthracyclines, event-free survival

Yanhong Liu,1 Qi Wang,1 Chuanlei Zheng,1,2 Zhengchun Huang,3 Jian Li,3 Ming Hao,1 Minghua Dong,1,2 Xiaoting Luo,2,4 Qingfeng Wu1,2 1School of Public Health & Healthcare Management, Gannan Medical University, Ganzhou, People’s Republic of China; 2Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of Basic Medicine Sciences, Gannan Medical University, Ganzhou, People’s Republic of China; 4School of General Practice Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Qingfeng Wu, Gannan Medical University, Rongjiang New District College Park, Ganzhou, Jiangxi, 341000, People’s Republic of China, Tel +86-797-8169713, Fax +86-797-8169600, Email wuqf2006@gmu.edu.cnPurpose: The prevalence of diabetes in China is increasing, influenced by economic and genetic factors, with varying rates across regions. The Hakka population in Ganzhou city has unique exposures compared to surrounding districts, while limited research reported the epidemiological characteristics of type 2 diabetes mellitus (T2DM) in this population. This study aims to investigate the prevalence and influencing factors of T2DM among the population, thereby establishing a robust foundation for disease prevention and control measures.Patients and Methods: In 2017, a multistage random sampling method selected 3028 individuals from Ganzhou City’s permanent resident population. Physical examinations, blood tests, and questionnaire surveys were conducted for data collection, with binary logistic regression analysis used to examine factors affecting T2DM prevalence.Results: A total of 2978 valid samples were included in this study. The average age of the surveyed population was 52.83± 7.88 years, comprising 966 males and 2012 females. The prevalence rates of T2DM were 11.8% and 12.9% in males and females, respectively, while the standardized prevalence rate was recorded as 9.1%. Logistic regression analysis revealed that age (Odds Ratio[OR]=1.05, 95% Confidence Interval [CI]:1.03– 1.06), hypertension (OR=2.22, 95% CI:1.71– 2.93), family history of diabetes (OR= 3.54, 95% CI: 2.58– 4.85), overweight (OR=1.73, 95% CI: 1.20– 2.48), high total cholesterol (OR=1.17, 95% CI:1.09– 1.27), elevated low-density lipoprotein cholesterol (OR=1.19, 95% CI:1.00– 1.40) and serum insulin (OR=1.05, 95% CI:1.03– 1.06) were identified as significant risk factors for T2DM, Conversely, a higher level of high-density lipoprotein cholesterol (OR=0.55, 95% CI:0.36– 0.84) was found to be inversely related to T2DM development.Conclusion: The prevalence of T2DM in Ganzhou city has significantly increased. The effective implementation of comprehensive management strategies aimed at addressing hypertension, overweight, dyslipidemia, and abnormal serum insulin level is essential for promoting overall well-being and efficiently controlling the prevalence of T2DM.Keywords: type 2 diabetes mellitus, cross-sectional studies, epidemiology, influence factors

Fei Zhou,1,2 Liyuan Liu,1,2 Fei Wang,1,2 Lixiang Yu,1,2 Yujuan Xiang,1,2 Chao Zheng,1,2 Shuya Huang,1,2 Zhen Yang,1 Zhigang Yu1,2 1Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of China; 2Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong, 250033, People’s Republic of ChinaCorrespondence: Zhigang Yu, Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of China, Tel +86-531-85875048, Email yzg@medmail.com.cnPurpose: Periductal mastitis (PDM) is a chronic inflammatory lesion of the breast with an unknown etiology, and it is difficult for clinicians to differentiate it from granulomatous lobular mastitis (GLM), although they have different treatment strategies and prognosis. This study aimed to investigate the differences in their clinicopathologic features to inform treatment strategies.Patients and Methods: Between 2011 and 2020, 121 patients diagnosed with PDM and 57 patients with GLM were retrospective analysis. Patient data were extracted on demographics, clinical presentation, pathologic characteristics, treatments and clinical response. Histopathological evaluations were performed on core needle biopsy specimens. Immunohistochemical stains using antibodies against CD3, CD4, CD8, CD20, and CD138 was performed to define immune cell infiltration.Results: PDM patients had a higher median age compared to GLM patients (38 vs 32, p< 0.001). PDM was primarily located in the areolar area, while GLM predominantly affected the peripheral quadrant of the breast (56.20% vs 75.44%, p< 0.001). Histopathologically, more ductal dilatation (90.08% vs 3.51%, p< 0.001), ductal wall thickening (47.93% vs 1.75%, p< 0.001), and ductal rupture (44.63% vs 5.26%, p< 0.001) were observed in PDM. GLM presented with significantly more granuloma (94.74% vs 10.74%, p< 0.001), microabscess (68.42% vs 28.93%, p< 0.001), and lipid vacuole (40.35% vs 8.26%, p< 0.001) formation than PDM. Immunohistochemical analysis revealed a significant presence of CD20+ B lymphocytes in PDM and a higher prevalence of CD8+ T lymphocytes in GLM, indicating differing immune responses. Treatment outcomes varied, with PDM patients responding well to surgery and anti-mycobacterial therapy, while GLM patients showed favorable responses to steroid therapy.Conclusion: PDM is a specific entity with a similar clinical presentation but distinct histopathological features and immune profiles to GLM. Further research is needed to elucidate the pathogenesis and optimize therapeutic approaches for these breast inflammatory conditions.Keywords: etiology, granulomatous lobular mastitis, immunology, pathology, periductal mastitis

Mengjuan Sun,1,&ast; Jun Wei,1,&ast; Yanhui Su,1,&ast; Yangjingwan He,1 Liang Ge,1 Yan Shen,1 Bohui Xu,2 Yanlong Bi,3 Chunli Zheng1 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of China; 2School of Pharmacy, Nantong University, Nantong, People’s Republic of China; 3Pediatric Intensive Care Unit, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunli Zheng; Yanlong Bi, Email zhengchunli@cpu.edu.cn; pulong123@163.comPurpose: The purpose of this study is to address the high mortality and poor prognosis associated with Acute Respiratory Distress Syndrome (ARDS), conditions characterized by acute and progressive respiratory failure. The primary goal was to prolong drug circulation time, increase drug accumulation in the lungs, and minimize drug-related side effects.Methods: Simvastatin (SIM) was used as the model drug in this study. Employing a red blood cell surface-loaded nanoparticle drug delivery technique, pH-responsive cationic nanoparticles loaded with SIM were non-covalently adsorbed onto the surface of red blood cells (RBC), creating a novel drug delivery system (RBC@SIM-PEI-PPNPs).Results: The RBC@SIM-PEI-PPNPs delivery system effectively extended the drug’s circulation time, providing an extended therapeutic window. Additionally, this method substantially improved the targeted accumulation of SIM in lung tissues, thereby enhancing the drug’s efficacy in treating ARDS and impeding its progression to ARDS. Crucially, the system showed a reduced risk of adverse drug reactions.Conclusion: RBC@SIM-PEI-PPNPs demonstrates promise in ARDS and ARDS treatment. This innovative approach successfully overcomes the limitations associated with SIM’s poor solubility and low bioavailability, resulting in improved therapeutic outcomes and fewer drug-related side effects. This research holds significant clinical implications and highlights its potential for broader application in drug delivery and lung disease treatment.Keywords: acute lung injury, simvastatin, respiratory distress syndrome, pH response

Yi Yang,1 Jingxian Wang,1 Qing Su,1 Jinhuan Yang,2,3 Zhiyuan Bo,2,3 Chongming Zheng,2,3 Yitong Xie,2,3 Kaiwen Chen,2,3 Juejin Wang,1 Gang Chen,2,3 Yi Wang1 1Department of Epidemiology and Biostatistics, School of Public Health, Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 3Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yi Wang, Department of Epidemiology and Biostatistics, School of Public Health, Wenzhou Medical University, Nanliu Road, Chashan Street, Ouhai District, Wenzhou City, Zhejiang Province, 325035, People’s Republic of China, Fax +86(577)-86699-358, Email wang.yi@wmu.edu.cn Gang Chen, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, Nanbaixiang Street, Ouhai District, Wenzhou City, Zhejiang Province, 325035, People’s Republic of China, Fax +86(577)-55579-555, Email chen.gang@wmu.edu.cnBackground: Primary liver cancer (PLC) is a fatal malignancy, sleep quality and gut microbiota were shown to be associated with PLC. However, the mechanism of how sleep quality affects PLC is unclear. This study aims to investigate the mediation/moderation effects of gut microbiota on sleep quality and the occurrence of PLC.Methods: The causality of sleep quality and the occurrence of PLC was detected through the Mendelian randomization (MR) analysis based on the data including 305,359 individuals (Finland Database) and 456,348 participants (UK Biobank). The primary method used for MR analysis was inverse-variance weighted analysis. Gut microbiota’ mediation/moderation effects were uncovered in the case–control study including 254 patients with PLC and 193 people with benign liver diseases through the mediation/moderation effect analyses. People’s sleep quality was evaluated through the Pittsburgh sleep quality index (PSQI).Results: Poor sleep quality could lead to PLC through the MR analysis (P = 0.026). The case–control study uncovered that Actinobacteria had mediation effects on the relationship between PSQI score, self-sleep quality, and the occurrence of PLC (P = 0.048, P = 0.046). Actinobacteria and Bifidobacterium could inhibit the development of PLC caused by short night sleep duration (P = 0.021, P = 0.022). Erysipelotrichales could weaken the influence of daytime dysfunction on PLC (P = 0.033). Roseburia modulated the contribution of nocturnal insomnia and poor sleep quality to PLC (P = 0.009, P = 0.017).Conclusion: Poor sleep quality was associated with PLC. Gut microbiota’ mediation/moderation effects on poor sleep quality and the occurrence of PLC prompted an insightful idea for the prevention of PLC.Keywords: primary liver cancer, sleep quality, gut microbiota, Mendelian randomization, mediation/moderation effect

Jingping Sun,1,2,&ast; Jun Zhang,3,&ast; Bailong Xin,1 Zekang Ye,1,2 Yaozhuo Cai,2 Ke Lu,2 Yuzhen Wang,2 Xueyao Lei,2 Chanjuan Zheng,2 Xueli Cai3 1Department of Neurology, the Municipal Central Hospital of Lishui, Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, Zhejiang, People’s Republic of China; 2Lishui Clinical Research Center for Neurological Diseases, Lishui, Zhejiang, People’s Republic of China; 3Zhejiang University, School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueli Cai, Department of Neurology, the Municipal Central Hospital of Lishui, Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, Zhejiang, People’s Republic of China, Email xueli_cai_official@126.comPurpose: Lipid-lowering therapy is integral in acute ischemic stroke (AIS), yet the connection between lipid parameters and parenchymal hemorrhage (PH) after endovascular treatment (EVT) for AIS is not well-defined. This research aims to assess the association between various lipid parameters and the PH risk following EVT.Patients and Methods: We examined a database of patients who underwent EVT for AIS between September 2021 and May 2023 retrospectively. Traditional and non-traditional lipid parameters were documented. PH was identified on dual energy computed tomography images within 48 h. We employed logistic regression analysis and restricted cubic splines to examine the association between various lipid parameters and the risk of PH. The predictive capacity of the lipid parameters for PH was evaluated by comparing the area under the curve.Results: The study included 384 patients, 65 of whom (17.7%) developed PH. After adjusting for potential confounders, only triglyceride was associated with PH among the traditional lipid parameters, while all non-traditional lipid parameters were related to PH. Based on ROC curve, the ratio of remnant cholesterol to high-density lipoprotein cholesterol (RC/HDL-C) exhibited the highest predictive capability for PH. Furthermore, our analysis revealed a significant nonlinear correlation between triglyceride, non-high-density lipoprotein cholesterol, RC, RC/HDL-C and PH risk.Conclusion: In assessing the risk of PH after EVT, non-traditional lipid parameters are often superior to traditional lipid parameters. It is recommended that routine evaluation of non-traditional lipid parameters could also be conducted in clinical practice as well.Keywords: endovascular treatment, hemorrhagic transformation, serum lipids

Jia-Meng Shao,&ast; Bing Shen,&ast; Zhi-Xiang Zhou, Lucia D’Angelo, Shea Michaela James, Jia-Feng Lin, Cheng Zheng Department of Cardiology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng Zheng; Jia-Feng Lin, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, East Section of Wenzhou Avenue, No. 1111, Wenzhou, Zhejiang Province, 325000, People’s Republic of China, Tel +86-13587688177 ; +86-13806685498, Email zhengcheng_wzmufey@163.com; linjiafeng_wzmcfey@163.comBackground: The role of total bilirubin (TBIL) in cardiovascular disease has been increasingly recognized in recent decades. Studies have shown a correlation between total bilirubin levels and the prognosis of patients after heart surgery. This study aimed to investigate the clinical significance of bilirubin elevation in persistent atrial fibrillation (PAF) patients who received radiofrequency catheter ablation (RFCA).Methods and Results: A total of 184 patients with PAF who received RFCA were retrospectively studied. Laboratory examinations and demographic data were analyzed to identify independent predictors of TBIL elevation. The relationship between TBIL and prognosis was further investigated. Our results indicated that TBIL increased significantly after RFCA. Multiple linear regression analysis showed that TBIL elevation owned a negative correlation with the percentile of low voltage areas (LVAs) in left atria (β=− 0.490, P< 0.001). In contrast, a positive correlation was observed with the white blood cell (WBC) ratio (β=0.153, P=0.042) and left atrial diameter (LAD) (β=0.232, P=0.025). It was found that postoperative TBIL levels increased and then gradually decreased to baseline within 5 days without intervention. The bilirubin ratio < 1.211 indicated the possibility of 1-year AF recurrence after ablation with a predictive value of 0.743 (specificity = 75.00%, sensitivity = 66.67%).Conclusion: Bilirubin elevation post PAF RFCA was a common phenomenon and was associated with 1-year recurrence of AF in PAF patients after RFCA.Keywords: bilirubin, atrial fibrillation, radiofrequency catheter ablation, oxidative stress, prognosis

Xiaoyu Wang,&ast; Yingqiao Zhu,&ast; Dan Liu, Lijun Zhu, Juan Tong, Changcheng Zheng Department of Hematology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changcheng Zheng, Department of Hematology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China, Tel/Fax +86-551-62284476, Email zhengchch1123@ustc.edu.cnIntroduction: COVID-19 infection has brought new challenges to the treatment of adult patients with immune thrombocytopenia (ITP). In adult ITP patients, there have been no relevant reports exploring the incidence, clinical characteristics, and risk factors of platelet elevation after COVID-19 infection.Materials and Methods: A total of 66 patients with previously diagnosed ITP from December 2022 to February 2023 in a single-center were collected and analyzed for this real-world clinical retrospective observational study.Results: In the platelet count increased group (n = 19), 13 patients (68.4%) were using thrombopoietin receptor agonists (TPO-RA) treatment at the time of COVID-19 infection; the median platelet count was 52 (2– 207) × 109/L at the last visit before infection and 108 (19– 453) × 109/L at the first visit after infection. In the platelet count stable group (n = 19) and platelet count decreased group (n = 28), 9 (47.4%) and 8 (28.6%) patients were using TPO-RA at the time of infection, respectively. ITP patients treated with TPO-RA had a significantly higher risk of increased platelet count than those not treated with TPO-RA at the time of infection (platelet count increased group vs platelet count decreased group: OR: 5.745, p = 0.009; platelet count increased group vs the non-increased group: OR: 3.616, p = 0.031). In the platelet count increased group, the median platelet count at 6 months post-infection was 67 (14– 235) × 109/L, which was significantly higher than the platelet level at the last visit before infection (p = 0.040).Conclusion: This study showed that some adult ITP patients had an increase in platelet count after COVID-19 infection, and this phenomenon was strongly associated with the use of TPO-RA at the time of infection. Although no thrombotic events were observed in this study, it reminds clinicians that they should be alert to the possibility of thrombotic events in the long-term management of adult ITP patients during the COVID-19 pandemic.Keywords: immune thrombocytopenia, thrombopoietin receptor agonists, COVID-19, thrombosis

Runqian Huang,1,&ast; Chunling Zheng,1,2,&ast; Guixiao Xu,1 Xuanwei Chen,1 Jingxian Shen,1 Siyue Mao1 1Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingxian Shen; Siyue Mao, Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of China, Tel/Fax +86-20-87343217, Email shenjx@sysucc.org.cn; maosiy@sysucc.org.cnObjective: To identify imaging features that help distinguish between HCCs and non-HCC malignancies assigned to LI-RADS M (LR-M) and evaluate the diagnostic performance of a LI-RADS with targetoid criteria using thin-rim arterial phase hyperenhancement (APHE).Materials and Methods: This retrospective study included 381 patients (387 observations) at high-risk for HCC who underwent enhanced-MRI before surgery. Three radiologists reviewed images for LI-RADS categorization of hepatic observations. Univariate and multivariate analysis was conducted to determine reliable features to differentiate between HCC and non-HCC malignancies among the LR-M lesions. The thin-rim (< 30%) APHE was defined based on the thickest thickness of rim APHE compared with the tumor radius, and a modified LI-RADS emphasizing thin-rim APHE as a specific feature of LR-M was established. We compared the diagnostic performance of modified LR-M and LI-RADS 5 (LR-5) with the conventional one.Results: Thin-rim APHE and targetoid diffusion-weighted imaging (DWI) were found as independent predictive factors of non-HCC malignancies, while enhancing capsule, thick-rim APHE and peripheral washout were noted as independent variables significantly associated with HCC of LR-M (P< 0.05). The noticeable diagnostic performance of thin-rim APHE in distinguishing non-HCC malignancies from HCCs using the ROC curve. Emphasizing thin-rim APHE on targetoid features, the modified LR-M revealed significantly superior specificity and accuracy (89.4% vs 81.1%, P=0.004; and 87.9% vs 82.2%, P=0.027, respectively) while maintaining high sensitivity (82.2% vs 86.0%; P=0.529) compared with the LR-M. Meanwhile, the modified LR-5 achieved greater sensitivity and accuracy (88.6% vs 79.7%, P=0.004; and 85.8% vs 80.1%, P=0.036, respectively) for diagnosing HCC, without compromising specificity (78.3% vs.81.1%; P=0.608) compared with the LR-5.Conclusion: Thin-rim APHE may be the specific imaging feature for differentiating non-HCC malignancies from HCCs within LR-M. The modified targetoid criteria emphasizing thin-rim APHE can improve the diagnostic performance of LI-RADS for hepatic malignancies.Keywords: hepatic tumors, malignant, targetoid feature, Rim APHE, liver imaging reporting and data system

Yingliang Wang,1,2,&ast; Shuguang Ju,1,2,&ast; Huimin Zhou,3,&ast; Yaowei Bai,1,2 Chen Zhou,1,2 Jiacheng Liu,1,2 Xiangjun Dong,1,2 Chuansheng Zheng1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China; 3Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangjun Dong; Chuansheng Zheng, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email dongxiangjun3100@163.com; hqzcsxh@sina.comPurpose: To explore the effect of calcium peroxide nanoparticles (CaO2 NPs) combined with programmed cell death protein 1 (PD-1) inhibitors in the treatment of liver cancer and its related mechanism.Methods: Hepa1-6 cells were cultured to construct the Hepa1-6 mouse liver cancer model. In vivo mechanism study, a unilateral tumor model was established. Eighteen tumor-bearing mice were randomly divided into the control group (intra-tumoral injection of PBS solution) and the experimental group (intra-tumoral injection of CaO2 NPs). A hypoxic probe, pH probe, and micro-CT were used to evaluate the effect of CaO2 NPs on improving hypoxia, neutralizing acidity, and inducing calcium overload within the tumor. To study the effect of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors, the bilateral tumor model was established. Forty tumor-bearing mice were randomly divided into the control group (intra-tumoral/intra-peritoneal injection of PBS solution), CaO2 NPs group (intra-tumoral injection of CaO2 NPs), PD-1 group (intra-peritoneal injection of PD-1 inhibitor), and the combination group (intra-tumoral injection of CaO2 NPs and intra-peritoneal injection of PD-1 inhibitors). The administered side was recorded as the proximal tumor. Tumor volume and body weight were measured every 2 days after treatment. On day 8, serum and tumor samples were collected. The immune factors in serum (Interferon-γ (IFN-γ), Tumour necrosis factor-α (TNF-α), Interleukin-2 (IL-2), and Interleukin-10 (IL-10)) and tumor tissue (IFN-γ and TNF-α) were detected by ELISA. H&E staining was used to detect tumor necrosis. Immunohistochemical staining was used to detect the amount of CD4+ and CD8+ T cells within the tumor. By analyzing the tumor volume, pathological indexes, and immune-related indexes, the effects of CaO2 NPs combined with PD-1 inhibitors on proximal and distal tumors were evaluated, and they mediated immunomodulatory effects (including local and systemic immunity), and their effects on tumor burden were studied. In addition, a unilateral tumor model was established to study the effect of CaO2 NPs combined with PD-1 inhibitors on survival time.Results: The results of in vivo mechanism study showed that CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors. The results of the study on the effect of CaO2 NPs combined with PD-1 inhibitor on proximal and distal tumors showed that, compared with the other three groups, the bilateral tumor burden of the combination group was significantly reduced, the intra-tumoral infiltration of CD8+ and CD4+ T cells were significantly increased, the secretion of anti-tumor immune factors in tumor and serum was increased, and the secretion of pro-tumor immune factors was decreased. Mice in the combination group showed the longest survival compared with the other groups.Conclusion: CaO2 NPs can improve hypoxia, neutralize acidity, and induce calcium overload within tumors, so as to reduce tumor burden and realize an immunosuppressive tumor transformation to a hot tumor, and play a synergistic role with PD-1 inhibitors in anti-liver cancer.Keywords: calcium peroxide nanoparticles, programmed cell death protein 1 inhibitor, Hepa1-6 model, tumor microenvironment, liver cancer

Junfeng Zhao,1,&ast; Shaoyu Hao,2,&ast; Ying Li,3 Xiaoman Liu,4 Zhaoxuan Liu,5 Chunhui Zheng,6 Dan Han1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 4Department of Oncology, BinZhou Medical University Affiliated Hospital, BinZhou Medical University, Binzhou, Shandong, People’s Republic of China; 5Department of Oncology, Zibo Centre Hospital, BinZhou Medical University, Zibo, Shandong, People’s Republic of China; 6Breast Cancer Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan Han, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Huayin District, Jinan, Shandong, People’s Republic of China, Tel +86-17862893373, Email echohandan@163.comPurpose: This study aimed to compare the efficacy and safety of neoadjuvant chemotherapy (NCT) and neoadjuvant immunotherapy combined with chemotherapy (NICT) combined with radical lung cancer resection for the treatment of patients with resectable non-small cell lung cancer (NSCLC). To adjust for confounding factors, we innovatively adopted two matching methods: propensity score (PS) and inverse probability of treatment weighting (IPTW).Patients and Methods: We conducted a retrospective analysis of the clinicopathological features and prognosis of patients with resectable NSCLC treated with NCT or NICT combined with radical lung cancer resection using propensity score matching (PSM) at a ratio of 1:1 and IPTW to balance potential bias.Results: After PSM, 116 pairs of patients who had undergone NCT or NICT were selected for the final analysis. The pathological complete remission (pCR) and major pathological remission (MPR) rates were significantly better in the NICT group than in the NCT group (pCR rate of 44.8% vs 2.6%, P< 0.001; MPR rate of 66.4% vs 20.7%, P< 0.001). No significant difference was seen between the NICT and NCT groups in terms of postoperative complications (12.1% vs 9.5%, P=0.182). Patients in the NICT group had significantly better disease-free survival (DFS) and overall survival(OS) than those in the NCT group ([3-year DFS: 75.2% vs 43.3%, P< 0.001] and [3-year OS: 91.5% vs 58.0%, P< 0.001]). Among all patients, those with postoperative pathology of pCR had better DFS (P< 0.001) and OS (P= 0.009). Patients with postoperative pathology of MPR had better DFS (P< 0.001) and OS (P< 0.001). The IPTW method yielded similar pathologic and prognostic results.Conclusion: Patients with resectable NSCLC treated with NICT had better pathological responses and prognosis, than those treated with NCT, and the safety profiles of NICT and NCT were similar.Keywords: neoadjuvant immunotherapy, neoadjuvant chemotherapy, non-small cell lung cancer, propensity score matching, inverse probability of treatment weighting, lung cancer resection, immune checkpoint inhibitor

Jiqian Jiang,1 Yan Wang,1 Dan Liu,1 Xiaoyu Wang,1 Yingqiao Zhu,1 Juan Tong,1 Erling Chen,1 Lei Xue,1 Na Zhao,1 Tingting Liang,2 Changcheng Zheng1 1Department of Hematology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCorrespondence: Changcheng Zheng, Department of Hematology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Road No. 17, Hefei, 230001, People’s Republic of China, Tel/Fax +86-551-62284476, Email zhengchch1123@ustc.edu.cnIntroduction: The BCL-2 inhibitor venetoclax has been widely used in the treatment of acute myeloid leukemia (AML); however, AML patients treated with venetoclax gradually develop resistance. The exportin-1 (XPO1) inhibitor selinexor can synergistically promote the antileukemia activity of venetoclax, but the mechanism remains unclear.Methods and Results: Annexin V/7-aminoactinomycin D assays were used to examine the effects of a combination of venetoclax and selinexor (VEN+SEL) on AML cell lines and primary AML cells. RNA sequencing and oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) determinations by a Seahorse XF analyzer were employed to investigate the molecular mechanism of the toxicity of the VEN+SEL combination to AML cells. The cytotoxicity of NK cell combined with VEN+SEL combination was assessed in vitro using flow cytometry. VEN+SEL enhanced the apoptosis of AML cells (KG-1A and THP-1) and primary AML samples in vitro. The ECAR and OCR results demonstrated that the VEN+SEL combination significantly inhibited glycolytic function. RNA sequencing of THP-1 cells demonstrated that DNA replication-related genes were downregulated after treatment with the VEN+SEL combination.Conclusion: This study indicated that selinexor can synergistically enhance the antileukemia activity of venetoclax in AML cells in vitro by inhibiting glycolytic function and downregulating DNA replication-related genes. Based on our experimental data, combining selinexor with venetoclax is an appropriate advanced treatment option for AML patients.Keywords: venetoclax, selinexor, acute myeloid leukemia, glycolytic function, DNA replication-related genes

Lijie Zhang,1,2,&ast; Wei Hong,1,2,&ast; Zizhuo Wang,1,2 Chuansheng Zheng,1,2 Bin Liang,1,2 Heshui Shi1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; 2Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, Hubei, China&ast;These authors contributed equally to this workCorrespondence: Bin Liang; Heshui Shi, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, Tel +86 27 85726432, Fax +86 27 85727002, Email bliang@hust.edu.cn; heshuishi@hust.edu.cnBackground: Population aging has emerged as a pressing global concern and a significant medical challenge. The use of transarterial chemoembolization (TACE) has been extensively employed for managing unresectable hepatocellular carcinoma (HCC). However, there is limited evidence regarding the safety and effectiveness of TACE specifically in individuals aged 80 years and above.Aim: To examine the safety and effectiveness of TACE in elderly patients (≥ 80 years) compared to younger patients (< 80 years) with HCC, and the potential risk factors that may impact the progression-free survival (PFS) for TACE were also identified.Methods: A retrospective analysis was conducted on a consecutive cohort of unresectable HCC patients who were initially treated with TACE. The patients were categorized into two groups based on the age at which they underwent TACE, and the efficacy and safety of the treatment were evaluated. The PFS was investigated, and the prognostic factors were analyzed using the Kaplan-Meier method and Cox proportional hazard models.Results: A total of 198 patients were included in this study, with 44 patients aged 80 years or older and 154 patients younger than 80 years. The cumulative risk of PFS after TACE was similar between the two groups (P = 0.800). In the multivariate analysis, a lower ECOG score (P = 0.039) and an earlier BCLC stage (P = 0.004) were identified as independent predictors of better PFS. Patients in both groups tolerated the TACE treatment well.Conclusion: The impact of aging on poor PFS is not significant. In patients with HCC, TACE therapy is both safe and effective for octogenarians, similar to younger patients. Furthermore, the better PFS is associated with a low ECOG score and an early BCLC stage.Keywords: transarterial chemoembolization, hepatocellular carcinoma, elderly patients, octogenarians

Cuifen Zhang,1,&ast; Ke Wang,1,&ast; Hong Zhang,1 Jingjing Liu,1 Chuangjie Zheng,1 Jiahao Tao,1 Lizhu Lin,2 Linzhu Zhai3 1the First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Cancer Center, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Cancer Center, Departments of Radiation Oncology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linzhu Zhai, Cancer Center, Departments of Radiation Oncology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 16 Jichang Road, Baiyun District, Guangzhou, 510405, People’s Republic of China, Tel +86-20-36591419, Email linzhuzhai@163.comAbstract: Patients treated with immune checkpoint inhibitors (ICIS) are prone to immune related adverse events (irAEs), making it important to pay attention to these adverse events. Herein, we report a case of onychopathy after treatment of extensive small cell lung cancer (ES-SCLC) with durvalumab; this is the first report of onychopathy caused by durvalumab in a patient with lung cancer. The change in the patient’s nails mainly manifested in the form of pigmentation and the thickening of the nails. Antifungal ointment was ineffective, and these changes were unrelated to malnutrition or any other factors. In addition, this case shows that onychopathy may occur within 2 years after treatment, indicating that these patients need long-term follow-up.Keywords: onychopathy, durvalumab, ES-SCLC, immune checkpoint inhibitors, immune-related adverse events

Yu-Bin Liu,1,2 Yun Liu,1,3 Lin Zhang,1 Xing-Chen Zhou,1 Bo-Yuan Ren,1 Can Zheng,1 Chun-Hua Hao,4 Wei-Ting Wang,4 Xia Xia,5 Gang-Qiao Zhou,1,3 Chu-Tse Wu,1 Ji-De Jin1 1Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 2Division of (Bio) Pharmaceutics, Institute of Zhejiang University - Quzhou, Zhejiang, People’s Republic of China; 3School of Medicine, Guizhou University, Guiyang, People’s Republic of China; 4Center for Pharmacodynamic Research, Tianjin Institute of Pharmaceutical Research, Tianjin, People’s Republic of China; 5Beijing SH Biotechnology Co., Ltd., Beijing, People’s Republic of ChinaCorrespondence: Chu-Tse Wu; Ji-de Jin, Email wuct@bmi.ac.cn; jinjide505@163.comBackground: Whether anticoagulant therapy should be used after spinal-cord injury (SCI) surgery was controversial. The anticoagulation characteristics of a newly developed anticoagulant, recombinant neorudin (EPR-hirudin (EH)), were explored using a rat model of SCI to provide a basis for clinical anticoagulation therapy of SCI.Methods: A rat model of SCI was developed by Allen’s method. Then, thrombosis in the inferior vena cava was induced by ligation. The low-bleeding characteristics of EH were explored by investigating dose–response and time–effect relationships, as well as multiple administration of EH, on thrombus formation complicated with SCI.Results: EH inhibited thrombosis in a dose-dependent manner by reducing the wet weight and dry weight of the thrombus. An inhibiting action of EH on thrombosis was most evident in the group given EH 2 h after SCI. After multiple intravenous doses of EH, thrombosis inhibition was improved to that observed with low molecular weight heparin (LMWH) (87% vs 90%). EH administration after SCI neither increased bleeding in the injured spine nor damaged to nerve function. Bleeding duration and activated partial thromboplastin time were increased in the high-dose EH group compared with that in the normal-saline group, but were lower than those in the LMWH group.Conclusion: EH can reduce thrombus formation in a rat model of SCI, and bleeding is decreased significantly compared with that using LMWH. EH may prevent thrombosis after SCI or spinal surgery.Keywords: recombinant neorudin, rat model, thrombosis, spinal-cord injury, low-bleeding anticoagulation

Haibin Shi,1 Minmin Chen,2 Caihong Zheng,2 Bian Yinglin,2 Bin Zhu2 1Department of Anesthesiology, the Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, Hangzhou Women’s Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Bin Zhu, Department of Anesthesiology, Hangzhou Women’s Hospital, 369 Kunpeng, Shangcheng District, Hangzhou City, Zhejiang Province, 310000, People’s Republic of China, Tel +86 13758136317, Email zhubinhfy@163.comPurpose: Paclitaxel-induced peripheral neuropathy (PIPN) constitutes a refractory and progressive adverse consequence of paclitaxel treatment, causing pain and sensory anomalies in cancer survivors. Although the gut-brain axis is involved in multiple disorders including cancer, its impact on peripheral pain conditions remains elusive. Thus, we assessed the importance of gut microbiota and related mechanisms in PIPN.Methods: By implementing fecal microbiota transplantation (FMT) in a rat PIPN model (ie, rats treated with paclitaxel; hereafter as PIPN rats), we explored the effect of gut microbiota on PIPN rats using multiple methods, including different behavioral tests, 16S ribosomal DNA (rDNA) sequencing, and biochemical techniques.Results: Sequencing of 16S rDNA revealed that the abundance of genera Bacteroides and UCG-005 increased, while that of genera Turicibacter, Clostridium sensu stricto 1 and Corynebacterium decreased in the PIPN rats. However, when treated with FMT using fecal from normal rats, the mechanical allodynia and thermal hyperalgesia in PIPN rats were significantly alleviated. In addition, FMT treatment reduced the expression of toll-like receptor 4 (TLR4), phospho-p38 mitogen-activated protein kinase (p-p38MAPK), and the astrocytic marker glial fibrillary acidic protein in the colon and spinal dorsal horn. TAK242 (a TLR4 inhibitor) significantly alleviated the behavioral hypersensitivity of PIPN rats and inhibited the TLR4/p38MAPK pathway in astrocytes in these rats.Conclusion: The gut microbiota played a critical role in PIPN. Future therapies treating PIPN should consider microbe-based treatment as an option.Keywords: astrocyte, gut microbiota, paclitaxel, p38, peripheral neuropathy, TLR4

Congying Zheng,&ast; Chengliang Mao,&ast; Kai Tang, Hang Shu Department of Neurosurgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou City, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hang Shu, Department of Neurosurgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106, Zhongshan Er Road, Guangzhou City, Guangdong Province, 510080, People’s Republic of China, Tel +86- 13902204543, Email zhengcongying@gdph.org.cnBackground: Glioblastoma (GBM) is the most common malignant primary brain tumour in adults. VSIG4 has been identified to be associated with GBM. We aimed to determine the downstream regulatory mechanisms of VSIG4 in GBM.Methods: Differential expression of VSIG4 was analysed using GEPIA. The expression of VSIG4 was assessed by RT-qPCR and its downstream genes were screened by transcriptome sequencing. The expression of pyroptosis-related proteins and the JAK2/STAT3 pathway was measured by Western blotting. GBM cell viability, migration, and invasion were detected using CCK-8, scratch, and Transwell assays. The levels of pyroptosis-related factors were measured using ELISA. The effect of VSIG4 on GBM tumour growth in vivo was explored by constructing a xenograft tumour model.Results: VSIG4 expression was upregulated in GBM. Functionally, silencing of VSIG4 inhibited proliferation, invasion, and migration of U251 and LN229 cells, and promoted pyroptosis. Mechanically, transcriptome sequencing revealed that the JAK2/STAT3 pathway might be a downstream regulator of VSIG4. Further studies proved that silencing of VSIG4 enhanced the expression of p-JAK2 and p-STAT3, and the JAK2/STAT3 pathway inhibitor relieved the suppression of VSIG4 silencing on GBM cell viability, invasion, and migration. Furthermore, in vivo experiments further validated that knockdown of VSIG4 inhibited the growth of GBM tumors.Conclusion: In GBM, silencing VSIG4 promoted pyroptosis and inhibited tumor progression by regulating the JAK2/STAT3 signaling pathway.Keywords: glioblastoma, VSIG4, JAK2/STAT3 pathway, pyroptosis

Jun Zhang, Li Zheng, Chenyao Zheng, Peihong Sun Department of Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Jun Zhang, Email zhangjun@mskyk.onaliyun.comPurpose: This study was designed to compare the clinical outcomes of three cylindrical treatment strategies using manifest, topographic, and Zhang & Zheng vector-compensated refraction (ZZ VR) cylinders, for topography-guided laser-assisted in situ keratomileusis (LASIK) and to identify the laser programming strategy that optimizes refractive astigmatism outcomes and visual acuity.Methods: Consecutive patients referred for therapeutic refractive surgery between March and September 2018 at a single center were prospectively analyzed. Using double-masked simple randomization, patients were randomly assigned to undergo treatment based on manifest cylinder, topographic cylinder, and ZZ VR cylinder strategies. Uncorrected distance visual acuity and astigmatic refraction were analyzed preoperatively and 6 months postoperatively.Results: A total of 138 eyes from 71 patients met the inclusion criteria. The manifest group consisted of 46 eyes in 24 patients, the topographic group consisted of 43 eyes in 22 patients, and the ZZ VR group consisted of 49 eyes in 25 patients. The absolute residual cylindrical refractions at 6 months postoperatively in these three groups were 0.69 ± 0.32 D, 0.58 ± 0.31 D, and 0.42 ± 0.19 D, respectively (P < 0.001; adjusted P < 0.01 for manifest vs ZZ VR, adjusted P = 0.08 for topographic vs ZZ VR). The percentages of postoperative absolute residual cylindrical power within 0.50 D in the manifest, topographic, and ZZ VR groups were 30.4%, 55.8%, and 59.2%, respectively (P = 0.01; adjusted P = 0.06 for manifest vs topographic, adjusted P = 0.02 for manifest vs ZZ VR).Conclusion: The ZZ VR strategy may achieve better outcomes, as determined by cylindrical correction and visual activity, during topography-guided LASIK.Clinical Trial Registration Number: ChiCTR1900025779.Keywords: astigmatism, corneal wavefront aberration, keratomileusis, laser in situ, refraction

Shan Jiang,1,2 Zhaolei Cui,3 Jianfeng Zheng,1 Qiaoling Wu,1 Haijuan Yu,1 Yiqing You,3 Chaoqiang Zheng,3 Yang Sun1 1Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, People’s Republic of China; 2College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China; 3Laboratory of Biochemistry and Molecular Biology Research, Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, People’s Republic of ChinaCorrespondence: Yang Sun, Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No. 420 Fuma Road, Fuzhou, Fujian, 350014, People’s Republic of China, Email sunyang@fjzlhospital.comBackground: Immunogenic cell death (ICD) can reshape the immune microenvironment of tumors. Driven by stressful pressure, by directly destroying tumor cells and activating the body’s adaptive immunity, ICD acts as a modulator of cell death, enabling the body to generate an anti-tumor immune response that produces a more effective therapeutic effect, while tumor cells are driven to kill. Hence, this research aimed to find and evaluate ICD-related genetic signatures as cervical cancer (CC) prognostic factors.Methods: Data of CC patients from the Tumor Genome Atlas (TCGA) were used as the basis to obtain immunogenic cell-death-related prognostic genes (IPGs) in patients with CC, using the least absolute shrinkage and selection operator and Cox regression screening, and the IPGs scoring system was constructed to classify patients into high- and low-risk groups, with the Gene Expression Omnibus (GEO) dataset as the validation group. Finally, the difference analysis of single-sample gene set enrichment analysis, tumor microenvironment (TME), immune cells, tumor mutational burden, and chemotherapeutic drug sensitivity between the high-risk and low-risk groups was investigated.Results: A prognostic model with four IPGs (PDIA3, CASP8, IL1, and LY96) was developed, and it was found that the group of CC patients with a higher risk score of IPGs expression had a lower survival rate. Single and multifactor Cox regression analysis also showed that this risk score was a reliable predictor of overall survival. In comparison to the low-risk group, the high-risk group had lower TME scores and immune cell infiltration, and gene set variation analysis showed that immune-related pathways were more enriched in the high-risk group.Conclusion: A risk model constructed from four IPGs can independently predict the prognosis of CC patients and recommend more appropriate immunotherapy strategies for patients.Keywords: ICD, cervical cancer, immunity, prognosis, immunotherapy response

Chunjiao Zheng, Ying Zou Skin and Cosmetic Research Department, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Ying Zou, Skin and Cosmetic Research Department, Shanghai Skin Disease Hospital, Tongji University School of Medicine, 1278 Baode Road, Jingan District, Shanghai, 200443, People’s Republic of China, Tel +86-18017336869, Fax +86-21-36803062, Email zouyingsh@163.comIntroduction: Allergen distribution has obvious geographical characteristics. Understanding local epidemiological data may provide evidence-based strategies for the prevention and management of disease. We investigated the distribution of allergen sensitization in patients with skin diseases in Shanghai, China.Methods: Data from tests for serum-specific immunoglobulin E were collected from 714 patients with three skin diseases who visited the Shanghai Skin Disease Hospital from January 2020 to February 2022. The prevalence of 16 allergen species, as well as age, sex, and disease-group differences in allergen sensitization, were investigated.Results: Dermatophagoides farinae and Dermatophagoides pteronyssinus were the most common aeroallergen species to cause allergic sensitization in patients with skin diseases, whereas shrimp and crab were the most common food-allergen species. Children were more susceptible to various allergen species. With regard to sex differences, males were sensitized to more allergen species than females. Patients suffering from atopic dermatitis were sensitized to more allergenic species than patients with non-atopic eczema or urticaria.Conclusion: Allergen sensitization in patients with skin diseases in Shanghai differed by age, sex, and disease type. Knowing the prevalence of allergen sensitization across age, sex, and disease type may help facilitate diagnostic and intervention efforts, and guide the treatment and management of skin diseases in Shanghai.Keywords: atopic dermatitis, non-atopic eczema, urticaria, specific immunoglobulin E, sensitization

Tao Sun,1,2,&ast; Yanqiao Ren,1,2,&ast; Bo Sun,1,2,&ast; Lei Chen,1,2 Licheng Zhu,1,2 Lijie Zhang,1– 3 Chuansheng Zheng1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei, People’s Republic of China; 3Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuansheng Zheng, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Tel +86-13329702158, Email hqzcsxh@sina.com Lijie Zhang, Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, People’s Republic of China, Email zlj_1226@163.comObjective: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs: sorafenib, lenvatinib, and apatinib) plus camrelizumab (TACE-TKIs-C) vs TACE combined with TKIs (TACE-TKIs) for advanced hepatocellular carcinoma (HCC).Methods: In this two-center retrospective study, patients with advanced HCC treated with TACE-TKIs-C or TACE-TKIs were enrolled between January 1, 2018, to October 1, 2020. A total of 260 eligible patients received TACE-TKIs-C (N=70) or TACE-TKIs (N=190). The differences in overall survival (OS), progression-free survival (PFS) and tumor response were compared between two groups. Propensity score matching (PSM) analysis was applied to reduce patient selection bias. The risk factors affecting OS or PFS were analyzed.Results: Fifty-three pairs of patients were matched after PSM analysis. Before PSM analysis, the median OS and PFS of TACE-TKIs-C were significantly longer than those of the TACE-TKIs (OS: not reached vs 12.0 months, P< 0.0001; PFS: 10.0 months vs 6.0 months, P< 0.0001). After PSM analysis, the median OS and PFS of TACE-TKIs-C were significantly longer than those of the TACE-TKIs (OS: Not reached vs 13.0 months, P< 0.0001; PFS: 9.0 months vs 6.0 months, P< 0.0001); the uni- and multivariate analysis revealed that TACE-TKIs-C treatment was a protective factor of OS and PFS. Grade 3 or 4 hypertension occurred in 14.3% of patients in the TACE-TKIs-C group and other high-grade toxic effects were infrequent.Conclusion: In patients with advanced HCC, TACE-TKIs-C may improve overall and progression-free survival outcomes over TACE-TKIs with manageable safety profile.Keywords: hepatocellular carcinoma, transarterial chemoembolization, tyrosine kinase inhibitors, camrelizumab, propensity score matching

Gaili Wang,1 Huizi Tian,2 Kai Kang,2 Shixian Feng,2 Weihao Shao,1 Xiaorui Chen,1 Caifang Zheng,1 Bowen Zhang,1 Pei Pei,3 Weidong Zhang1 1Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 2Henan Provincial Center for Disease Control and Prevention, Zhengzhou, Henan, 450016, People’s Republic of China; 3Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, 100191, People’s Republic of ChinaCorrespondence: Weidong Zhang, Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China, Tel +86-0371-67781964, Email imooni@163.comObjective: Little is known about the effect of age at first childbirth on lung function. We aimed to investigate the association between age at first childbirth and lung function in Chinese women and further test whether this association is mediated by body mass index (BMI).Methods: This cross-sectional study is a partial survey of the China Kadoorie Biobank (CKB) which was conducted in Xinxiang City, Henan Province between 2004 and 2008. A total of 16,584 postmenopausal women aged 30– 79 years were enrolled. Multiple linear and logistic regression were used to investigate the association between age at first childbirth and lung function and overweight/obesity. The mediation analysis was performed using the PROCESS procedure for SPSS.Results: The mean (SD) age at first childbirth was 23.1 (2.7) years. Women with first childbirth aged ≤ 19 years and 20– 22 years had lower lung function than women who gave first childbirth aged 23– 25 years. Per 1-year increase in the age at first childbirth was associated with a 3.31 mL increase in FEV1 (95% CI = 1.27– 5.35), 3.91 mL increase in FVC (95% CI = 1.63– 6.18), 0.15% increase in FEV1, % predicted (95% CI = 0.05– 0.24) and 0.14% increase in FVC, % predicted (95% CI = 0.05– 0.22). There was no clear association between age at first childbirth and FEV1/FVC ratio. BMI played a contribution to the association between age at first childbirth and FEV1 and the proportion was 16.4% (indirect effect: β = 0.65, 95% CI = 0.46– 0.89; total effect: β = 3.96, 95% CI = 1.92– 5.99). Similarly, the proportion to FVC, FEV1, % predicted, and FVC, % predicted was 25.0%, 16.6%, and 25.0%, respectively.Conclusion: Early age at first childbirth was associated with lower lung function and BMI mediated the association. It is important to test lung function and popularize the knowledge of weight control in women who gave first childbirth at an early age.Keywords: first childbirth, lung function, body mass index, mediation, postmenopausal women

Jiamiao Yang,&ast; Chao Zheng,&ast; Yan Wang, Ling Yang, Lianyong Liu Department of Endocrinology, Shanghai Punan Hospital of Pudong New District, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianyong Liu; Ling Yang, Department of Endocrinology, Shanghai Punan Hospital of Pudong New District, No. 279, Linyi Road, Pudong New District, Shanghai, 200125, People’s Republic of China, Tel +86-18930502267 ; Tel +86-18930502267, Email chinallu@163.com; yangjiamiao0719@163.comObjective: The present study explores the relationship between glycemic excursion and bone turnover markers.Methods: A total of 250 patients with type 2 diabetes mellitus (T2DM) (142 female and 108 male patients) were enrolled in this study. All participants underwent 72 hours of continuous glycemic monitoring to evaluate the mean amplitude of glycemic excursions (MAGE) of each person. Bone turnover markers and other biochemical data were measured for each patient. Linear regression was performed to explore the relationship between bone turnover markers and glycemic excursion. A value of P < 0.05 was considered statistically significant.Results: MAGE was negatively correlated to N-terminal propeptide of type 1 collagen (P1NP) female: [odds ratios (95% confidence interval) (OR (95% CI)), − 2.516 (− 5.389, 0.356)]; male: [− 2.895, (− 6.521, − 0.731)] and C-terminal telopeptide fragments of type-I collagen (β-CTX) female [− 0.025, (− 0.036, 0.005)]; male [− 0.043, (− 0.082, 0.003)]. MAGE was still negatively correlated with β-CTX female [− 0.036, (− 0.198, − 0.030)]; male [− 0.048, (− 0.089, − 0.007)] after adjusting for clinical data and biochemical indices.Conclusion: An independent negative relationship between glycemic excursion and bone turnover markers in patients with T2DM was identified in this study.Keywords: bone turnover markers, continuous glucose monitoring, glycemic variability, mean amplitude of glycemic excursions, type 2 diabetes mellitus

Chunlan Zheng,1,2,&ast; Yanan Peng,1,2,&ast; Haizhou Wang,1,2 Youwei Wang,1,2 Lan Liu,1,2,&ast; Qiu Zhao1,2,&ast; 1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 2Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan Liu; Qiu Zhao, Tel +86-027-67812888, Fax +86 027-67812892, Email lliugi@whu.edu.cn; qiuzhao@whu.edu.cnBackground: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with an immunosuppressive Tumor microenvironment (TME). Ferroptosis plays an essential role in tumor proliferation, invasion, and metastasis. However, the relationship between ferroptosis and TME of HCC has remained elusive.Methods: Differentially expressed ferroptosis-related genes (DE FRGs) between normal liver tissues and HCC tissues were obtained from The Cancer Genome Atlas (TCGA). On this basis, we identified the molecular subtypes mediated by DE FRGs and TME cell infiltration. Next, a predictive signature was established to quantity the ferroptosis-related characteristics by performing the least absolute shrinkage and selection operator Cox regression analyses. Univariate and multivariate COX analyses determined the independent prognostic factors. Finally, the expression stability of 3 ferroptosis-related signature genes was verified in cancer and paracancerous normal tissues of HCC.Results: We identified three different molecular subtypes and found that the subtype with the better prognosis was associated with high enrichment of immune- and metabolic-related hallmark signaling pathways and high infiltration of immune cells in TME. The signature was considered to be an independent prognostic factor. We also found that the signature can reflect the infiltration characteristics of different immune cells in TME. Immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), regulatory T cells, and type 17 T helper cells were significantly enriched in the high-risk group. The analysis data of immune checkpoints and tumor mutation load indicated that the signature had great potential in predicting Immunotherapy response and chemotherapeutic sensitivity. In addition, the overexpression of 3 ferroptosis-related signature genes was confirmed in HCC tissues and HCC cell lines. Ferroptosis inducer RSL3 inhibited the proliferation of HCC cells and was a potential cancer immunotherapy agent.Conclusion: These findings enhanced our understanding of the regulatory mechanism of ferroptosis in HCC and provided new insights into evaluating prognosis and developing more effective Immunotherapy and chemotherapy strategies.Keywords: hepatocellular carcinoma, ferroptosis, prognosis, immunotherapy, tumor mutational burden