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Yuanyuan Su,1,* Ning Lu,2,* Pei Wang,3,* Qian Li,2 Hua Wen,2 Jie Zhang,2 Ling Fan,2 Jie Li,2 Zhaoxiang Yu,4 Manli Cui,2 Mingxin Zhang2 1Department of General Medicine, the People’s Hospital of Yubei District of Chongqing, Chongqing, People’s Republic of China; 2Department of Gastroenterology, the First Affiliated Hospital of Xi’an Medical College, Xi’an, Shaanxi, People’s Republic of China; 3Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 4Department of General Surgery, the First Affiliated Hospital of Xi’an Medical College, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Manli Cui, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, Email cuiml1587@163.com; Mingxin Zhang, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, Email zmx3115@xiyi.edu.cn.Objective: This study aims to explore the nexus between students’ psychological well-being and the manifestation of gastrointestinal symptoms (GISs) amid the health lockdown enforced in Xi’an, focusing on the student populace of Xi’an Medical College and Shaanxi University of Traditional Chinese Medicine.Materials and methods: A survey encompassing psychological parameters and GISs was administered to a randomized cohort of 1327 college students drawn from Xi’an Medical College and Shaanxi University of Traditional Chinese Medicine. The survey instrument was developed utilizing the Questionnaire Star platform. Subsequent to data collection, analysis was performed using GraphPad Prism 9 and SPSS 22.0.Results: Comparative analysis revealed statistically significant disparities (P < 0.05) in various GISs between the periods during and preceding the health lockdown, encompassing symptoms such as nausea/vomiting, acid reflux, postprandial fullness/early satiety, anorexia, decreased appetite, bloating, abdominal discomfort, abdominal pain, diarrhea, and constipation. Notably, the mean score for Generalized Anxiety Disorder 7 (GAD-7) was 3.31± 3.92, indicating mild anxiety, while the mean score for Patient Health Questionnaire-2 (PHQ-2) was 1.15± 1.28, suggesting mild depression. Detailed evaluation of anxiety revealed prevalence rates of 34% among respondents, with 34.2% of these individuals reporting concurrent GISs, while among those evaluated for depression (38.8% of the sample), 44.2% reported concurrent GISs. Furthermore, multiple linear regression analysis unveiled a negative correlation between GISs during the health lockdown and lifestyle scores, while positive correlations were observed with GISs preceding the lockdown, anxiety, and depression. The formulated multiple linear regression equation for GISs during the health lockdown is delineated as follows: 14.693– 0.342 life style + 0.725GISs before health lockdown + 0.218anxiety + 0.564 depression.Conclusion: This investigation underscores the substantial impact of anxiety and depression on the student body, accentuating their role in precipitating GISs during health lockdown situations. The psychological well-being of medical students during exigent circumstances such as natural disasters warrants heightened attention, necessitating proactive measures aimed at emotional regulation to mitigate the onset of GISs.Keywords: COVID-19, health lockdown, gastrointestinal symptoms, anxiety, depression

Lu Zhu,1,&ast; Jing Li,1,&ast; Zhao-Qin Wang,1,2,&ast; Yun-Jia Gu,1 Guo-Na Li,3 Wen-Jia Wang,1 Guang-Bin Pen,1 Qi Li,1 Meng-Die Wu,1 Hui-Rong Liu,1,2 Yan Huang,1,2 Lu-Yi Wu1 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3School of Acupuncture, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu-Yi Wu, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai City, 200437, People’s Republic of China, Email luyitcm@163.com Yan Huang, Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, No. 650 Wanping South Road, Xuhui District, Shanghai City, 200030, People’s Republic of China, Email huangyan@shutcm.edu.cnObjective: Moderate-to-severe pain is the most common clinical symptom in patients with hepatocellular carcinoma (HCC).This trial aimed to analyze the clinical efficacy of Transcutaneous electrical acupoint stimulation (TEAS) in patients of HCC with severe pain and provide a reliable reference for optimizing the clinical diagnostic and therapeutic strategies of HCC.Methods: A total of 104 eligible patients were randomly allocated to experimental and control groups in a ratio of 1:1.The treatment was administered for 1 week continuously. Patients in both groups were followed up 1 week after the end of the treatment.The primary outcome measure was the Numerical Rating Scale (NRS) score, whereas the secondary outcome measures included Brief Pain Inventory BPI-Q3, Q4, Q5 scores, analgesic dose, frequency of opioid-induced gastrointestinal side effects, Karnofsky Performance Status (KPS), Quality of Life Scale - Liver Cancer (QOL-LC), and Brief Fatigue Inventory (BFI) scores.Results: The NRS scores of experimental group was significantly lower after treatment and at the follow-up than baseline (average P< 0.01), there were also statistical differences between the groups at the above time points (average P< 0.01). BPI-Q3, -Q4, and -Q5 scores in the experimental group were decreased after treatment when compared with those before treatment (average P< 0.01). Furthermore, there were significant improvements of gastrointestinal side effects, KPS, QOL-LC and BPI in the experimental group after treatment, and the above results were statistically significant compared to the control group.Conclusion: 7-day TEAS treatment can significantly enhance the analgesic effect and maintain for the following week, also reduce the incidence of gastrointestinal side effects caused by opioids, and improve the quality of life of patients with moderate-to-severe HCC-related pain, which has reliable safety and certain clinical promotion value.Keywords: hepatocellular carcinoma pain, transcutaneous electrical acupoint stimulation, cancer pain, randomized controlled trial

Haonan Guan,&ast; Guoyou Zhang,&ast; Qiqi Li, Jie Lian, Zhaoyang Dong, Lian Zhu, Kaiyan Xiao Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaiyan Xiao, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, People’s Republic of China, Tel +86 021 23271699, Fax +86 021 63136856, Email xky7026@163.comAbstract: Xanthomas are well-circumscribed skin lesions that are commonly seen in patients with familial hypercholesterolemia (FH). The aim of this report is to present a rare case of multiple large tuberous and tendinous xanthomas. A 17-year-old female patient in this report presented with multiple asymptomatic and papulo-nodular masses in both sides of palms, elbows, buttocks, knees, and Achilles tendons. Surgical removal of the masses was carried out in combination with lipid-lowering therapy. A following up of 3 months showed all wounds were healing well, and no recurrence of masses was observed. Therefore, for patients with xanthomas related with familial hypercholesterolaemia, lipid-lowering therapy has reportedly reduced the size of masses, but surgical treatment may be essential for large xanthomas caused pain or limitation of daily activities.Keywords: soft-tissue tumors, lipoprotein, atorvastatin, foam cells, lipid-lowering therapy

Xiaoguang Xiao,1 Jianhai Sun,2 Dongsheng Zhang,3 Linjun Li,4 Haibo Zhou,5 Yongjun Li,6 Quan Li,7 Zhongshi He,8 Yang Fu,9 Qiwen Duan,10 Guping Zheng,11 Ze Tang,12 Qian Chu,1,&ast; Yuan Chen1,&ast; 1Department of Oncology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Oncology, Hubei Zhongshan Hospital, Wuhan, Hubei, People’s Republic of China; 3Department of Oncology, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei, People’s Republic of China; 4Department of Oncology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, People’s Republic of China; 5Department of Oncology, Yichang Central People’s Hospital, Yichang, Hubei, People’s Republic of China; 6Department of Oncology, Yichang Second People’s Hospital, Yichang, Hubei, People’s Republic of China; 7Department of Oncology, Xiangyang Central Hospital, Xiangyang, Hubei, People’s Republic of China; 8Department of Oncology, Xiangyang No 1 People’s Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei, People’s Republic of China; 9Department of Oncology, Xiangyang Hospital of Traditional Chinese Medicine, Xiangyang, Hubei, People’s Republic of China; 10Department of Oncology, Taihe Hospital, Shiyan, Hubei, People’s Republic of China; 11Department of Oncology, Xiaogan Central Hospital, Xiaogan, Hubei, People’s Republic of China; 12Department of Oncology, Huangshi Central Hospital, Huangshi, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Chu; Yuan Chen, Email qianchu@tjh.tjmu.edu.cn; chenyuantj2023@126.comBackground: Studies have shown that oral oxycontin tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycontin tablets for opioid titration of cancer pain.Patients and Methods: Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST).Results: A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5[95% CI:2.5– 11.5] hours vs.16.0 [95% CI:11.5– 22.5] hours; p< 0.001). The frequency (median; interquartile) of breakthrough pain (Btp) over 24 hours was significantly lower in the PCSA group (2.5;2.0– 3.5) than in the oxycontin group.(3.0; 2.5– 4.5) (p=0.04). The pain was evaluated by numeric rating scale (NRS) score at 12 hours after the start of titration. The pain score (median; interquartile) was significantly lower in the PCSA versus the oxycontin group (2.5;1.5– 3.0) vs 4.5;3.0– 6.0) (p=0.02). The equivalent dose of oral morphine (EDOM) for a successful titration was similar in both groups (p=0.29), but there was a significant improvement in quality of life (QoL) in both groups (p=0.03). No between-group difference in the incidence of opioid-related adverse effects was observed (p=0.32).Conclusion: Compared with oral oxycontin tablet, the use of PCSA with hydromorphone achieved a shorter titration duration for patients with cancer pain (p< 0.001), without significantly increasing adverse events (p=0.32).Keywords: cancer pain, opioid titration, oxycontin tablets, hydromorphone, patient-controlled subcutaneous analgesia

Xiuying Li,1 Xin Wang,1 Xiuwu Qu,1 Ningning Shi,1 Qinqing Li,1 Zhifang Yan,1 Yandong Li,2 Yingli Wang3 1Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of China; 2Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China; 3Shanxi Modern Traditional Chinese Medicine Engineering Laboratory, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of ChinaCorrespondence: Yandong Li; Yingli Wang, Email liyandongzhongnan@163.com; wyl@sxtcm.edu.cnPurpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease involving synovial inflammation and joint destruction. Although therapeutic drugs for RA have some efficacy, they usually cause severe side effects and are expensive. RA is characterized by synovial hyperplasia, intra-articular hypoxia, upregulated expression of matrix metalloproteinases, and excessive accumulation of reactive oxygen species. The adverse microenvironment further aggravates activated macrophage infiltration. Therefore, controlling the microenvironment of diseased tissues and targeting the activated macrophages have become new therapeutic targets in RA patients.Methods: Here, microenvironment-targeting micelles (PVGLIG-MTX-Que-Ms) were synthesized using the thin film hydration method. In the inflammatory microenvironment, PVGLIG was cleaved by the highly expressed MMP-2, PEG5000 was eliminated, MTX was exposed, macrophage activation was targeted, and Que enrichment was enhanced. The cytotoxicity, targeting, antioxidant, and anti-inflammatory properties of drug-loaded micelles were tested in vitro. The drug-loaded micelles were used to treat CIA rats. In vivo targeting, expression of serum inflammatory factors, immunohistochemistry of the articular cartilage, and changes in immunofluorescence staining were observed.Results: The developed micelles had a particle size of (89.62 ± 1.33) nm and a zeta potential of (− 4.9 ± 0.53) mV. The IC50 value of PVGLIG-MTX-Que-Ms (185.90 ± 6.98) μmol/L was significantly lower than that of free Que (141.10 ± 6.39) μmol/L. The synthesized micelles exhibited slow-release properties, low cytotoxicity, strong targeting abilities, and significant anti-inflammatory effects in vitro. In vivo, the drug-loaded micelles accumulated at the joint site for a long time. PVGLIG-MTX-Que-Ms significantly reduced joint swelling, improved bone destruction, and decreased the expression of serum inflammatory factors in CIA rats.Conclusion: The smart-targeting micelles PVGLIG-MTX-Que-Ms with strong targeting, anti-inflammatory, cartilage-protective, and other multiple positive effects are a promising new tool for RA treatment.Keywords: matrix metalloproteinases, quercetin, macrophages, methotrexate, anti-inflammatory

Yufei Wang,1,&ast; Xiaoteng Ma,1,&ast; Zhiqiang Yang,1,2 Qiuxuan Li,1 Yujie Zhou,1,3 Fei Gao,1,3 Zhijian Wang1,3 1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Ministry of Education, Beijing, People’s Republic of China; 2Cardio-Metabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3The Key Laboratory of Remodeling-Related Cardiovascular Disease, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Wang; Fei Gao, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, the Key Laboratory of Remodeling-related Cardiovascular Disease, Beijing Institute of Heart Lung and Blood Vessel Disease, Anzhen Avenue &num;2, Chaoyang District, Beijing, 100029, People’s Republic of China, Email zjwang1975@hotmail.com; fgaomd@163.comBackground and Aims: Elevated eosinophils typically indicate hypersensitive inflammation; however, their involvement in cardiovascular events remains incompletely understood. We investigated the association between the absolute eosinophil count (AEC) and major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Additionally, we determine whether the integration of AEC with the SYNTAX II score could improve predictive ability.Methods and Results: The AECs of 1711 patients with ACS undergoing PCI from June 2016 to November 2017 were analyzed on admission. All recruitments were splitted into three groups based on AEC tertiles and 101 participants underwent one or more noteworthy outcomings. The association between AEC and MACCEs (defined as a composite of cardiovascular death, myocardial infarction [MI], and stroke) was tested by Cox proportional-hazards regression analysis. After adjusting for confounders, AEC was independently associated with MACCEs (HR 11.555, 95% CI: 3.318– 40.239). Patients in the lowest AEC tertile (T1) as a reference, those in the higher tertiles had an incrementally higher risk of MACCEs (T3: HR 1.848 95% CI: 1.157– 2.952; P for trend=0.008). Inclusion of AEC enhanced the predictive accuracy of the SYNTAX II score for MACCEs (AUC: from 0.701 [95% CI: 0.646– 0.756] to 0.728 [95% CI: 0.677– 0.780]; DeLong’s test, P = 0.020).Conclusion: AEC is independently linked to MACCEs in ACS patients who underwent PCI, and adds incremental predictive information to the SYNTAX II score.Keywords: absolute eosinophil count, SYNTAX I score, SYNTAX II score, cardiovascular and cerebrovascular events, acute coronary syndrome, percutaneous coronary intervention

Qi Li,1,&ast; Cong Gao,1 Xinrui Zhao,1 Jiahui Li,1 Qinghong Shen,1 Li Chen2,&ast; 1Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Li, Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email 1589898345@qq.com Li Chen, Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China, Email cswtth@163.comObjective: The study was aimed to investigate the influence factor between preoperative inflammatory indicators and drainage tube retention time in patients with breast cancer.Methods: This retrospective study enrolled 121 patients with breast cancer who were undergoing surgery between October 2020 and June 2021. The enumeration data were used the Chi-square test, and the measurement data were used the t-test analysis. The univariate and multivariate logistic regression models were performed to access the risk factors for affecting drainage tube retention time in patients with breast cancer. The receiver operating characteristic curve (ROC) was performed to test the prediction effect of the model.Results: Through the median extraction time of postoperative drainage tube retention time, all patients were divided into two groups: drainage tube retention time (DTRT) < 13 (d) and drainage tube retention time (DTRT) ≥ 13 (d). The results showed that type of surgery, total lymph nodes (TLN), pathological T stage, NLR were related to the drainage tube retention time (P< 0.05). Moreover, the univariate and multivariate logistic regression analysis performed that Hb, type of surgery, pathological T stage, chest wall drainage tube, NRI were the independent risk predictors of affecting drainage tube retention time. Furthermore, a significant correlation existed between NRI and drainage tube retention at different times (P < 0.05).Conclusion: NRI is an independent risk factor for postoperative drainage tube extraction time and can effectively predict the probability of drainage tube retention time. Thus, it can also provide personalized nursing intervention for patients with breast cancer after drainage tube retention time and the rehabilitation process.Keywords: breast cancer, inflammatory indicator, drainage tube, operation, nutritional indicator

Yue Zhang,1,&ast; Qi Li,1,&ast; Jiang-Lin Xiang,2 Xing-Hua Li,1 Jing Li3 1Department of Radiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Infectious Disease, Chongqing University Three Gorges Hospital, Chongqing, 404000, People’s Republic of China; 3Medical Department, Liangjiang New Area Renhe Community Health Service Center, Chongqing, 401147, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Li, Medical Department, Liangjiang New Area Renhe Community Health Service center, Chongqing, 401147, People’s Republic of China, Tel +86 18716469389, Email lijing_345678@163.com Xing-Hua Li, Tel +86 18584603726, Email 595904844@qq.comPurpose: To investigate potential differences in clinical and computed tomography (CT) features between patients with the SARS‐CoV‐2 Omicron variant and the original strain.Patients and Methods: This retrospective study included 69 hospitalized patients infected with Omicron variant from November to December 2022, and 96 hospitalized patients infected with the original strain from February to March 2020 in Chongqing, China. The clinical features, CT manifestations, degrees of lung involvement in different stages on CT, and imaging changes after the reverse-transcription polymerase chain reaction (RT-PCR) results turned negative were compared between the two groups.Results: For clinical features, patients with Omicron were predominantly old people and females, without manifestation of any clinical symptoms, who had low serum levels of C-reactive protein and procalcitonin. Shorter interval from symptoms onset to initial CT scan was observed in Omicron patients compared to patients with the original strain (all P < 0.05). For CT features, patients with Omicron were more likely to present with round-like opacities and tree-in-bud pattern (all P < 0.05), but less likely to exhibit a diffuse distribution, patchy and linear opacities, as well as vascular enlargement pattern (all P < 0.05). The Omicron group was more susceptible to exhibiting lower CT involvement scores in each stage (all P < 0.05) and imaging progression after the RT-PCR results turned negative (P < 0.001).Conclusion: Patients infected with the Omicron variant exhibited less severe changes on chest CT compared to those infected with the original strain. Furthermore, imaging progression under low viral load conditions was more common in patients with Omicron than in those with the original strain.Keywords: severe acute respiratory syndrome coronavirus-2, pneumonia, computed tomography

Qingchen Li,1– 3,&ast; Xiaolin Xie,1,2,&ast; Jiasong Yang,1,2,4 Peng Gao,5 Wensheng Li1,2,4 1Shanghai Aier Eye Hospital, Aier Eye Hospital Group Co. Ltd, Shanghai, 201103, People’s Republic of China; 2Shanghai Aier Eye Institute, Aier Eye Hospital Group Co. Ltd, Shanghai, 201103, People’s Republic of China; 3Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, 410011, People’s Republic of China; 4Aier School of Ophthalmology, Central South University, Changsha, Hunan Province, 410015, People’s Republic of China; 5Department of Ophthalmology, Shanghai Tenth People’s Hospital of Tongji University, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Li, Shanghai Aier Eye Hospital, Aier Eye Hospital Group Co. Ltd, No. 83 Wuzhong Road, Xuhui District, Shanghai, 201103, People’s Republic of China, Email drlws@qq.comPurpose: To observe the outcome of bilateral femtosecond laser-assisted clear lens extraction with trifocal intraocular lens (IOL) implantation for presbyopia correction and evaluate its feasibility in early presbyopic adults.Methods: Prospective case series of eyes with clear crystalline lenses that underwent femtosecond laser-assisted lens extraction and trifocal IOL (Acrysof IQ PanOptix, Model TFNT00, Alcon) implantation between 2021 and 2023 were followed up for at least 3 months after surgery. Outcome measures included monocular uncorrected visual acuity at near (UNVA, 40 cm), intermediate (UIVA, 60 cm), and distance (UDVA, 5 m), monocular manifest refraction, corrected distance visual acuity (CDVA), defocus curve assessment, and spectacle independence at both near and distance.Results: A total of 60 eyes from 30 consecutive patients were included, and their mean age was 50.4± 6.5 years. After surgery, the mean UNVA (LogMAR) increased from 0.28± 0.16 to 0.08± 0.07, UIVA increased from 0.25± 0.12 to 0.09± 0.06, and UDVA increased from 0.27± 0.21 to 0.01± 0.08. The enhancements of UNVA, UIVA and UDVA were all significant (P < 0.05). The optometric results showed that the mean postoperative spherical equivalent (SE) was − 0.21± 0.24 D, and the mean postoperative CDVA (LogMAR) was − 0.00± 0.06. The preoperative spectacle independences at near and distance were 46.7% (14/30) and 56.7% (17/30), respectively, and both increased to 100% at 3 months after surgery.Conclusion: Satisfactory visual outcomes and safe surgical procedures were observed in this study, which demonstrate that bilateral femtosecond laser-assisted clear lens extraction with PanOptix IOL implantation could be a feasible approach for presbyopia correction in working-age Chinese patients.Keywords: presbyopia-correcting, clear lens extraction, refractive lens exchange, trifocal intraocular lens, refractive surgery

Qiwei Li,1 Zhiyun Zhang,1,2 Jiajia Fang1 1Department of Neurology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang Province, 322000, People’s Republic of China; 2Department of Neurology, The Mianyang Central Hospital, Mianyang, Sichuan Province, 621000, People’s Republic of ChinaCorrespondence: Jiajia Fang, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, People’s Republic of China, Email fangjjiaj@zju.edu.cnAbstract: Epilepsy is a prevalent neurological disorder among women globally, often requiring long-term treatment. Hormonal fluctuations in women with epilepsy (WWE) can have reciprocal effects on epilepsy and antiseizure medications (ASMs), posing significant challenges for WWE. Notably, WWE commonly experience endocrine alterations such as thyroid dysfunctions, low bone metabolism, and reproductive hormone irregularities. On the one hand, the presence of hormones in women with epilepsy affects their susceptibility to epilepsy as well as the metabolism of antiseizure medications in various ways. On the other hand, epilepsy itself and the use of antiseizure medications impact the production, secretion, and metabolism of hormones, resulting in low fertility, increased risk of pregnancy complications, negative offspring outcomes, and so on. In order to develop more precise treatment strategies in the future, it is necessary to comprehend the explicit relationships between hormones, epilepsy, and antiseizure medications, as well as to elucidate the currently known mechanisms underlying these interactions.Keywords: women with epilepsy, antiseizure medications, endocrine, hormonal changes

Yuting Kang,1,&ast; Qiujie Li,2,&ast; Yao Yao,3 Chao Xu,2 Zhuoran Qiu,2 Wei Jia,1,3 Gang Li,1,3 Pengtao Wang1 1Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3Center of Medical Laboratory, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang Li; Pengtao Wang, General Hospital of Ningxia Medical University, Technology Building 601, 804 Shengli Road, Yinchuan, People’s Republic of China, Tel +86-0951-6744462 ; +86-0951-6743330, Email gone.lee@163.com; wangpengtao2021@163.comPurpose: The objective of this study was to determine the clinical distribution, in vitro antifungal susceptibility and underlying resistance mechanisms of Aspergillus fumigatus (A. fumigatus) isolates from the General Hospital of Ningxia Medical University between November 2021 and May 2023.Methods: Antifungal susceptibility testing was performed using the Sensititre YeastOne YO10, and isolates with high minimal inhibitory concentrations (MICs) were further confirmed using the standard broth microdilution assays established by the Clinical and Laboratory Standards Institute (CLSI) M38-third edition. Whole-Genome Resequencing and RT-qPCR in azole-resistant A. fumigatus strains were performed to investigate the underlying resistance mechanisms.Results: Overall, a total of 276 A. fumigatus isolates were identified from various clinical departments, showing an increasing trend in the number of isolates over the past 3 years. Two azole-resistant A. fumigatus strains (0.72%) were observed, one of which showed overexpression of cyp51A, cyp51B, cdr1B, MDR1/2, artR, srbA, erg24A, and erg4B, but no cyp51A mutation. However, the other strain harbored two alterations in the cyp51A sequences (L98H/S297T). Therefore, we first described two azole-resistant clinical A. fumigatus strains in Ningxia, China, and reported one azole-resistant strain that has the L98H/S297T mutations in the cyp51A gene without any tandem repeat (TR) sequences in the promoter region.Conclusions: This study emphasizes the importance of enhancing attention and surveillance of azole-resistant A. fumigatus, particularly those with non-TR point mutations of cyp51A or non-cyp51A mutations, in order to gain a better understanding of their prevalence and spread in the region.Keywords: Aspergillus fumigatus, azole resistance, cyp51A mutation, tandem repeat sequences

Yuye Chen,1 Yue Liu,2 Hong Lv,1 Qian Li,1 Jingjia Shen,1 Weiyun Chen,2 Jia Shi,1 Chenghui Zhou3 1Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College/National Center for Cardiovascular Diseases, Beijing, 100037, People’s Republic of China; 2Department of Anesthesiology, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 3Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of ChinaCorrespondence: Chenghui Zhou, Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-137-1889-4919, Email chenghuizhou@vip.163.com Jia Shi, Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College/National Center for Cardiovascular Diseases, No. 167 North Lishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email shijia@fuwai.comBackground: The potential myocardial protective effect of nicorandil (NICD) in patients undergoing percutaneous coronary intervention has been established. However, its efficacy in the context of cardiac surgery remains controversial. The present study aimed to evaluate the myocardial protective effect of perioperative NICD use in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).Methods: We retrospectively gathered data from patients undergoing cardiac bypass surgery between 12/2018 and 04/2021 in Fuwai Hospital. Subsequently, the patients were divided into two groups, NICD group and non-nicorandil (non-NICD) group. A 1, 3 propensity score matching (PSM) was conducted. The primary outcome was the incidence of myocardial injury. The secondary outcomes included the mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, duration of chest drainage, the drainage volume, the total cost, the incidence of acute kidney injury (AKI), and the incidence of acute liver injury (ALI). Subsequently, we divided the entire population into two distinct subgroups based on their administration of NICD, and performed a comprehensive subgroup analysis.Results: A total of 2406 patients were ultimately included in the study. After PSM, 250 patients in NICD group and 750 patients in non-NICD group were included in the analysis. Perioperative NICD reduced the incidence of myocardial injury (47.2% versus 38.8%, P=0.025). Our subgroup analysis revealed that preoperative NICD administration not only provided myocardial protection benefits (45.7% vs 35.8%, OR 0.66, 95% CI [0.45– 0.97], P=0.041), but also demonstrated statistically significant reduction in ALI, the ICU and hospital LOS, and the duration of chest drainage (all P< 0.05).Conclusion: The perioperative NICD administration may confer myocardial protection in patients undergoing cardiac surgery with CPB. Furthermore, the preoperative utilization of NICD has the potential to mitigate the incidence of postoperative ALI, a reduction in the ICU and hospital LOS, and the duration of chest drainage.Keywords: nicorandil, cardiopulmonary bypass, perioperative myocardial injury, acute kidney injury, acute liver injury

Xiaoming Yang,&ast; Zhongda Liu,&ast; Xiaojing Liu, Quan Li, Hui Huang, Zunjing Zhang Department of Respiratory and Critical Care Medicine, Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui, 323000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zunjing Zhang, No. 800 Zhongshan Road, Liandu District, Lishui, Zhejiang Province, People’s Republic of China, Tel +8613884387661, Email 382149034@qq.comPurpose: Sangju-Yin, supplemented with some drugs, has frequently demonstrated therapeutic efficacy against colds, albeit its effect on Mycoplasma pneumoniae (MP) infection remains unknown. Therefore, we aimed to elucidate the treatment efficacy and influencing factors of a Sangju cough mixture on MP infection in adults.Patients and Methods: Between January 2021 and December 2022, 150 adult patients with MP infection at the Lishui Hospital of Traditional Chinese Medicine Affiliated with Zhejiang University of Traditional Chinese Medicine were assigned to the treatment (administered Sangju cough mixture and moxifloxacin tablets) or the control (administered moxifloxacin tablets) groups.Results: When compared with the control group, the treatment group exhibited significantly improved traditional Chinese medicine syndrome scores, increased CD4+ T cell levels, and decreased CD8+ T cell levels (all P < 0.05). After 7 days of treatment, the negative conversion rate of the MP-specific immunoglobulin M (MP-IgM) antibody of the treatment group was not significantly different from that of the control group (P > 0.05); however, after 14 days of treatment, the rate was significantly higher in the treatment group (P < 0.05). The univariate regression analysis revealed that combined chronic respiratory disease, failure to take Sangju cough mixture, combined pneumonia, Nutritional Risk Screening 2002 (NRS 2002) score of at least 3 points, and age were associated with the negative conversion of the MP-IgM antibody (all P < 0.05). Nevertheless, the multivariate regression model revealed that the NRS 2002 score of at least 3 points was not an independent risk factor (P > 0.05).Conclusion: Sangju cough mixture can improve symptoms, accelerate the negative conversion time of MP-IgM antibody, and promote rehabilitation of the patients.Keywords: Mycoplasma pneumoniae infection, Sangju cough mixture, moxifloxacin, negative conversion time, influencing factors

Huanhuan Zhu, Chen Chen, Luhan Geng, Qing Li, Chengning Zhang, Lin Wu, Bo Zhang, Suyan Duan,&ast; Changying Xing,&ast; Yanggang Yuan&ast; Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanggang Yuan, Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Tel/Fax +86-25-6813-6462, Email ygyuan@njmu.edu.cnBackground: Mounting evidence suggests that mitochondrial dysfunction contributes to lupus nephritis (LN) pathogenesis. Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) mediating pyruvate transport from the cytoplasm to the mitochondrial matrix, determines the cell survival and cellular energy supply. Here, we aimed to investigate the association of mitochondrial pyruvate carrier expression with the clinical and histological features in LN.Methods: Patients with biopsy-proven proliferative LN (class III and class IV, n=18) and membranous LN (class V, n=18) were included. Expression of MPC1 and MPC2 were examined by immunohistochemistry. MPC protein levels in the two groups were evaluated by the Student’s t-test. Correlation analysis between MPC levels and clinicopathological features was performed by Spearman’s rank correlation.Results: Both MPC1 and MPC2 were exclusively expressed in renal tubules of enrolled LN. Significantly lower MPC1 and MPC2 were observed in patients with proliferative LN compared to membranous LN. In addition, the MPC1 and MPC2 were negatively correlated with SLEDAI-2K score, renal function, and renal pathology activity index.Conclusion: Both MPC1 and MPC2 were localized in renal tubules, and decreased MPC content was more pronounced in proliferative LN than membranous LN. MPC levels were significantly correlated with renal functions and renal pathology activity.Keywords: lupus nephritis, mitochondrial pyruvate carrier, proliferative, membranous, tubulointerstitial lesions

Qiyu Wang,1,&ast; Ying Gao,2,&ast; Qiang Li,1,&ast; Ao He,1 Qinglin Xu,1 Yongbin Mou1 1Department of Oral Implantology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, 210008, People’s Republic of China; 2Department of Stomatology, the 964 Hospital, Changchun, Jilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Li; Yongbin Mou, Department of Oral Implantology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, &num;30 Zhongyang Road, Nanjing, 210008, People’s Republic of China, Tel +86 25 83620236, Fax +86 25 83620202, Email njuliqiang@smail.nju.edu.cn; yongbinmou@163.comBackground: Nanovaccines have emerged as a promising vaccination strategy, exhibiting their capacity to deliver antigens and adjuvants to elicit specific immune responses. Despite this potential, optimizing the design and delivery of nanovaccines remains a challenge.Methods: In this study, we engineered a dendritic mesoporous silica-based nanocarrier enveloped in a metal-phenolic network (MPN) layer containing divalent manganese ions and tannic acid (MSN@MT). This nanocarrier was tailored for antigen loading to serve as a nanovaccine, aiming to activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in dendritic cells (DCs). Our experimental approach encompassed both cellular assays and mouse immunizations, allowing a comprehensive evaluation of the nanovaccine’s impact on DC activation and its influence on the generation of antigen-specific T-cell responses.Results: MSN@MT demonstrated a remarkable enhancement in humoral and cellular immune responses in mice compared to control groups. This highlights the potential of MSN@MT to effectively trigger the cGAS-STING pathway in DCs, resulting in robust immune responses.Conclusion: Our study introduces MSN@MT, a unique nanocarrier incorporating divalent manganese ions and tannic acid, showcasing its exceptional ability to amplify immune responses by activating the cGAS-STING pathway in DCs. This innovation signifies a stride in refining nanovaccine design for potent immune activation.Keywords: nanocarrier, metal-phenolic network, manganese ions, tannic acid

Songli Ruan,1,&ast; Xin Wang,2,&ast; Chengjia Zhao,3,&ast; Qian Li,2 Wing Ming Li,2 Guohua Zhang,4,5 Jianshe Pan,4 Xue Yang2 1Mental Health Education and Guidance Center of College Students, Henan University of Urban Construction, Pingdingshan, People’s Republic of China; 2JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 3School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Psychiatry, The Affiliated Kangning Hospital, Wenzhou, People’s Republic of China; 5Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Yang, JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China, Email sherryxueyang@cuhk.edu.hkBackground: Enhancing abstinence motivation of drugs is an effective strategy for the rehabilitation of people who used drugs and prevention of drug use relapse. However, little is known about its risk and protective factors. This study aimed to examine the potential intrapersonal (ie, impulsivity, depression, anxiety, sleep quality) and interpersonal factors (ie, perceived social support) of abstinence motivation among people who completed the community rehabilitation treatment.Methods: A total of 222 participants (mean age = 43; male = 89.2%) were recruited from eleven communities located in Wenzhou, China. Data were collected using a self-reported questionnaire in counselling room settings between April and June 2021.Results: The proportions of participants with depression, anxiety, and poor sleep quality were 38.8%, 19.5%, and 21.2%, respectively. Age and family history of physical disease were significant background factors of abstinence motivation. Impulsivity, depressive symptoms, anxiety symptoms, and poor quality of sleep were negatively associated with abstinence motivation. Perceived social support from family and important others was positively associated with abstinence motivation. Structural equation modeling fitted the data well in which impulsivity and perceived social support were both associated with abstinence motivation indirectly through mental health problems.Conclusion: The identified psychosocial factors should be addressed in community rehabilitation treatment and follow-up service to enhance abstinence motivation and the long-term effectiveness of the treatment.Keywords: abstinence motivation to drugs, mental health problems, personality, social support, community-based rehabilitation treatment, Chinese people who used drugs

Ruijie Wang,1,2 Quan Li,1 Pengxin Wu,3 Ke Ren,3 Yan Li,1 Yang Wang,3 Huadong Zhu,1 Chuanzhu Lv2– 4 1Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences (No. 2019RU013), Hainan Medical University, Haikou, People’s Republic of China; 3Emergency Medicine Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, People’s Republic of ChinaCorrespondence: Chuanzhu Lv; Huadong Zhu, Email Lvchuanzhu677@126.com; zhuhuadong1970@126.comBackground: In sepsis, the lungs are one of the most severely affected organs, usually resulting in acute lung injury (ALI). Capsaicin (CAP) is a natural compound found in chili peppers that has pain-relieving and anti-inflammatory properties. Here, we report that nanoparticles containing capsaicin and iron (Fe-CAP NPs) exhibited anti-inflammatory effects in the treatment of ALI.Methods: The morphological characteristics of nanozymes were detected. RAW 264.7 cells were divided into four groups: control, lipopolysaccharide (LPS), CAP+LPS and Fe-CAP+LPS groups. The expression of inducible nitric oxide synthase (iNOS), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) was assessed by immunofluorescence, Western blot, and enzyme-linked immunosorbent assay (ELISA). Nuclear factor kappa-B (NF-κB) expression was determined by Western blot. C57 mice were divided into control, LPS, CAP+LPS and Fe-CAP+LPS groups. Interleukin-6 (IL-6) and iNOS expression in the lung was detected by Western Blot. IL-6 and TNF-α expression in serum was detected by ELISA. Extravasated Evans blue, histopathological evaluation and wet-to-dry (W/D) weight ratio were used to assess pulmonary capillary permeability. The blood and major organs (heart, liver, spleen, lung and kidney) of mice were tested for the toxicity of Fe-CAP NPs.Results: In the LPS group, TNF-α, iNOS, p-NF-κB and p-IKBα expression increased. However, their expression was significantly decreased in the Fe-CAP+LPS group. TGF-β expression showed the opposite trend. In vivo, IL-6 and iNOS expression was notably increased in the lungs of LPS group of mice but decreased with Fe-CAP pretreatment. Fe-CAP significantly ameliorated lung EB leakage, improved the histopathology of lung tissue and reduced the W/D weight ratio. The nanoparticles showed non-cytotoxicity, when studying these biological activities.Conclusion: Fe-CAP NPs could alleviated inflammation by inhibiting the expression of pro-inflammatory factors in macrophages, increasing the expression of anti-inflammatory factors, and alleviating lung tissue damage.Keywords: capsaicin, sepsis, macrophage, nanoparticles, iron

Wenbo Wu,1,&ast; Xiaoli Yu,2,&ast; Jiaxiang Sun,3 Yuanyuan Han,3 Yuanye Ma,1 Guoqing Zhang,1 Qingming Ma,4 Qiang Li,3 Hongfei Xiang1 1Department of Orthopedics, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Department of Anesthesiology, the Affiliated Hospital of Qingdao University, Qingdao, 266100, People’s Republic of China; 3College of Physics, Center for Marine Observation and Communications, Qingdao University, Qingdao, 266021, People’s Republic of China; 4Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao, 266021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfei Xiang; Qingming Ma, Tel +86-532-61807860, Email xianghf@qdu.edu.cn; qma@qdu.edu.cnBackground: As a broad-spectrum antitumorigenic agent, doxorubicin (DOX) is commonly used as a chemotherapeutic drug for treating osteosarcoma (OS). Still, it is associated with significant cell toxicity and ineffective drug delivery, whereas the zeolite imidazolate framework is extensively applied in the biomedical field as a carrier owing to its favorable biocompatibility, high porosity, and pH-responsiveness. Therefore, we need to develop a drug delivery platform that can effectively increase the antitumorigenic effect of the loaded drug and concurrently minimize drug toxicity.Methods: In this study, a Fe3O4@ZIF-8 nanocomposite carrier was prepared with ZIF-8 as the shell and encapsulated with Fe3O4 by loading DOX to form DOX- Fe3O4@ZIF-8 (DFZ) drug-loaded magnetic nanoparticles. Then, we characterized and analyzed the morphology, particle size, and characteristics of Fe3O4@ZIF-8 and DFZ by TEM, SEM, and Malvern. Moreover, we examined the inhibitory effects of DFZ in vitro and in vivo. Meanwhile, we established a tumor-bearing mouse model, evaluating its tumor-targeting by external magnetic field guidance.Results: DFZ nanoparticles possessed have a size of ~110 nm, with an encapsulation rate of 21% and pH responsiveness. DFZ exerted a superior cytostatic effect and apoptosis rate on K7M2 cells in vitro compared to DOX(p< 0.01). In animal experiments, DFZ offers up to 67% tumor inhibition and has shown a superior ability to induce apoptosis than DOX alone in TUNEL results(p< 0.01). Tumor-targeting experiments have validated that DFZ can be effectively accumulated in the tumor tissue and enhance anticancer performance.Conclusion: In summary, the DFZ nano-delivery system exhibited a more substantial anti-tumorigenic effect as well as superior active tumor targeting of DOX- Fe3O4@ZIF-8 compared to that of DOX alone in terms of biocompatibility, drug loading capacity, pH-responsiveness, tumor-targeting, and anti-tumorigenic effect, indicating its chemotherapeutic application potential.Keywords: osteosarcoma chemotherapy, zeolite imidazolate framework, PH-responsive, nanocarriers, tumor targeting

Boyi Yu,1– 4 Xuanyi Lu,5 Xianglong Feng,1– 4 Ting Zhao,1– 4 Jiaxin Li,1– 4 Yudie Lu,5 Fei Ye,1– 4 Xiongxiong Liu,1– 4 Xiaogang Zheng,1– 4 Zheyu Shen,5 Xiaodong Jin,1– 4 Weiqiang Chen,1– 4 Qiang Li1– 4 1Biomedical Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, People’s Republic of China; 2Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, People’s Republic of China; 3Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, Gansu Province, People’s Republic of China; 4College of Life Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 5School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Xiaodong Jin; Weiqiang Chen, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou, Gansu Province, 730000, People’s Republic of China, Tel +86-931-4969316, Fax +86-931-8272100, Email jinxd@impcas.ac.cn; chenwq7315@impcas.ac.cnIntroduction: Radiotherapy is a widely recognized first-line clinical treatment for cancer, but its efficacy may be impeded by the radioresistance of advanced tumors. It is urgent to improve the sensitivity of radioresistant tumors to radiotherapy. In this work, gadolinium oxide nanocrystals (GONs) were utilized as radiosensitizers to enhance the killing effect and reinforce the immune activation of X-ray irradiation on 4T1 breast cancer cells in vitro and in vivo.Methods: 1.0 T small animal MR imaging (MRI) system was employed to trace GONs in vivo, while 225 kVp X-ray irradiation equipment was utilized for investigating the radiosensitization of GONs in 4T1 breast cancer cells in vitro and in vivo. Western blot, quantitative real-time PCR (RT-qPCR), immunohistochemistry, immunofluorescence, clonal survival assay, flow cytometry and reactive oxygen species assay were used to explore the biological mechanism of GON sensitization.Results: GONs exhibited exceptional utility as contrast agents for both in vivo and in vitro MRI imaging. Interestingly, a single dose of 8.0 Gy X-rays together with GONs failed to confer superior therapeutic effects in tumor-bearing mice, while only 3.0 Gy × 3 fractions X-rays combined with GONs exhibited effective tumor growth inhibition. Moreover, fractionated X-ray irradiation with GONs demonstrated a superior capacity to activate the cGAS-STING pathway.Discussion: Fractionated X-ray irradiation in the presence of GONs has demonstrated the most significant activation of the anti-tumor immune response by boosting the cGAS-STING pathway. Keywords: gadolinium oxide nanoparticles, magnetic resonance imaging, radiosensitization, cGAS-STING pathway, 4T1 breast cancer cells

Min Jiang,1,&ast; NanNan Pang,2,&ast; Jing Wang,1 Zheng Li,1 Dan Xu,1 Jing Jing,1 Dan Chen,3 Fengsen Li,1 Jianbing Ding,4 Qifeng Li5 1Xinjiang Key Laboratory of Respiratory Disease Research, Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830011, Xinjiang, People’s Republic of China; 2CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, People’s Republic of China; 3School of Public Health, Xinjiang Medical University, Urumqi, 830017, Xinjiang, People’s Republic of China; 4Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, 830011, Xinjiang, People’s Republic of China; 5Xinjiang Institute of Pediatrics, Xinjiang Hospital of Beijing Children’s Hospital, Children’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830011, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qifeng Li, Xinjiang Institute of Pediatrics, Xinjiang Hospital of Beijing Children’s Hospital, Children’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830054, People’s Republic of China, Tel +86-991 3056239, Fax +86-991 3056237, Email liqiqi521@sina.comBackground: Studying the potential etiology and pathogenesis of tuberculosis-associated chronic obstructive pulmonary disease (TOPD) from an autoimmunity perspective may provide insights into peripheral blood autoantibodies and immune cells, as well as their interactions.Methods: This study examined the serum autoantibody repertoire in healthy individuals, patients with chronic obstructive pulmonary disease (COPD), patients with pulmonary tuberculosis (TB), and TOPD patients using the HuProtTM protein chip. Autoantigens in the peripheral blood of TOPD patients were verified using ELISA assay. Various epitopes and immune simulation were predicted using bioinformatic methods. Flow cytometry was employed to detect macrophages(M&phis;), T cells, and innate lymphoid cells (ILCs) in the peripheral blood.Results: COPD patients displayed distinct alterations in their IgG and IgM autoantibodies compared to the other groups. GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses revealed that these autoantibodies were associated with regulating macrophages, T cells, and B cells. ELISA results confirmed the upregulation of expression of proliferating cell nuclear antigen (PCNA), Mitogen-Activated Protein Kinase 3 antigen (MAPK3), and threonine protein kinase 1 antigen (AKT1) proteins in the peripheral blood of TOPD patients. Bioinformatic analysis predicted multiple potential epitopes in Th, CTL, and B cells. Immune simulation results demonstrated that PCNA, MAPK3, and AKT1 can activate innate and adaptive immune responses and induce the expression of different cytokines, such as IFN-g and IL-2. Furthermore, data obtained from flow cytometry assay revealed an upregulation in the face of Th1 cells in the peripheral blood of TOPD patients.Conclusion: Tuberculosis infection can effectively induce autoimmune responses, contributing to increased expression of Th1 cells and associated cytokines, ultimately leading to immune dysregulation. Furthermore, the accumulation of pulmonary inflammatory response facilitates the progression of TOPD and is helpful for the clinical diagnosis and the development of targeted therapeutic drugs for this disease.Keywords: chronic obstructive pulmonary disease, COPD, autoantibody, autoimmunity, inflammatory phenotype

Zhitao Chen,1,&ast; Yahui He,2,&ast; Chenchen Ding,3 Jun Chen,2 Yangjun Gu,1 Min Xiao,1 Qiyong Li1 1Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, 310003, People’s Republic of China; 2School of Medicine, Zhejiang Chinese Medical University Zhejiang Shuren College, Hangzhou, 310003, People’s Republic of China; 3Child and Adolescent Psychology, Affiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiyong Li, Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, 848&num; Dongxin Road, Hangzhou, Zhejiang Province, 310003, People’s Republic of China, Tel +86-0571-56757021, Email liqiyong@zju.edu.cnBackground: Pancreatic cancer is a deadly disease with a low five years survival rate, and chemotherapy remains the standard treatment for advanced cases. However, the efficacy of chemotherapy alone is limited, and there is a need for new treatment options. Recently, immune checkpoint inhibitors (ICIs), particularly programmed death-1 (PD-1) inhibitors, have shown promising results in various cancers, including pancreatic cancer. In this study, we explore the safety and efficacy of PD-1 inhibitors in combination with chemotherapy for advanced pancreatic cancer.Materials and Methods: A retrospective analysis was conducted on clinical data from 27 patients with advanced pancreatic cancer who were administered a combination of anti-PD-1 antibody and gemcitabine plus nab-paclitaxel (GnP) regimen. The study evaluated the safety of the treatment as well as the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).Results: In this study, treatment with a combination of anti-PD-1 antibody and GnP regimen for pancreatic cancer resulted in partial response (PR) for 10 out of 27 (37.04%) patients, stable disease (SD) for 10 (37.04%) patients, and progressive disease (PD) for 7 (25.92%) patients. The study found that the median OS (mOS) for these patients was 16.4 months [standard error (SE) = 1.117, 95% confidence interval (CI) 14.211– 18.589], while the median PFS (mPFS) was 6.4 months (SE = 1.217, 95% CI 3.981– 8.752). Subgroup analysis revealed that pancreatic cancer patients’ Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0 vs 1) and treatment cycles (≤ 6 cycles vs > 6 cycles) significantly affected OS and PFS. Patients experienced mostly grade 1– 2 adverse events (AEs), which were relieved through clinical treatment.Conclusion: The combination of GnP with anti-PD-1 antibodies shows promise as a potential treatment option for advanced pancreatic cancer.Keywords: pancreatic cancer, immune checkpoint inhibitors, PD-1, gemcitabine, nab-paclitaxel, chemotherapy

Deyong Tan,1– 4 Jianfeng Han,5 Qingzhi Sun,5 Xing Cheng,5 Juan Liu,5 Jia Liu,5 Qing Li,1– 4 Lizhong Dai5 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008 People’s Republic of China; 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078 People’s Republic of China; 3Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410078 People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, 410008 People’s Republic of China; 5Sansure Biotech Inc, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Qing Li, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, People’s Republic of China, Tel +86 731 84805380, Fax +86 731-82354476, Email liqing9251026@csu.edu.cn Lizhong Dai, Sansure Biotech Inc, No. 680 Lusong Road, Changsha, Hunan, People’s Republic of China, Tel +86 73188883176, Email lizhongd@sansure.com.cnObjective: In this study, we conducted a multi-center research on six common lower respiratory tract pathogens using novel multiplex fluorescence quantitative polymerase chain reaction (PCR), and investigated the additional diagnostic value of this method, to provide a molecular diagnostic basis for clinical practice.Methods: From March 2019 to October 2021, a total of 2047 respiratory sputum samples were collected from Hunan Provincial People’s Hospital (the First Affiliated Hospital of Hunan Normal University), Hunan Provincial Children’s Hospital, Jiangxi Provincial Children’s Hospital, and Wuhan Infectious Disease Hospital. The samples were analyzed using a novel multiplex fluorescence quantitative PCR method for Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Legionella pneumophila, and Staphylococcus aureus. The results were compared to the results of bacterial culture and sequencing, as well as the results of third-party kits.Results: Compared to the bacterial culture method, 2047 samples were detected with a sensitivity of 100%, a specificity of 72.22%, and an overall compliance rate of 81.91%. Compared to the sequencing method, the positive agreement percentage was 99.88%, the negative agreement percentage was 97.72%, and the overall agreement rate was 98.84%. Compared to similar control reagents, the positive agreement percentage was 100%, negative agreement percentage was 79.79%, and overall compliance rate was 96.19%.Conclusion: The multiplex fluorescence PCR method has the advantages of simultaneously detecting multiple pathogenic bacteria and reducing the duration of pathogen culture identification. Combined detection can increase the detection rate, which has favorable performance and application prospects.Keywords: bacterial infection, lower respiratory tract, melting curve, multiplex PCR, rapid diagnosis

Qi Li,1 Yongli Wang,2,&ast; Huawen Liu,3 Hailang Peng,4 Jianglin Xiang,2,&ast; Shuliang Guo4,&ast; 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Infectious Disease, Chongqing University Three Gorges Hospital, Chongqing, 404000, People’s Republic of China; 3Department of Oncology, Chongqing University Three Gorges Hospital, Chongqing, 404000, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuliang Guo, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Tel +86-23-89012097, Email GUOSL_999@163.com Jianglin Xiang; Yongli Wang, Tel +86 13896328822; +86 15213571077, Email 1448026879@qq.com; wyl068@foxmail.comPurpose: To investigate the computed tomography (CT) findings of SARs-CoV-2 Omicron variant in relation to respiratory viral loads determined by cycle threshold values in reverse-transcription polymerase chain reaction (RT-PCR).Materials and Methods: From October 2022 to November 2022, 74 hospitalized patients with Omicron were included in this retrospective study. The radiological features, CT involvement scores in relation to the respiratory viral load, and factors associated with imaging progression (IP) after the RT-PCR results turned negative were analyzed.Results: The most common CT patterns of Omicron were multiple round-like or patchy ground-glass opacity (GGO) or mixed GGO in the peripheral or diffuse areas. The grading of CT involvement scores exhibited an inverse pattern compared to viral loads from day 1 to day 8 and from day 13 to day 20 after diagnosis. Among the 65 patients with complete imaging data, 45 (69.23%) showed IP with clinical warning indicators of disease exacerbation negative in 34 and positive in 11. Patients with IP were older than those with non-IP (NIP); the erythrocyte sedimentation rates, procalcitonin levels, and D-dimer levels on admission of patients with IP were significantly higher than those of patients with NIP, whereas the immunoglobulin (Ig) G antibody level on admission and CT involvement score on initial CT of patients with IP were significantly lower than those of patients with NIP (all P < 0.05).Conclusion: For patients with Omicron, the IP of lung abnormalities is common when the viral load decreases. Under these circumstances, paying attention to clinical warming indicators of disease progression may contribute to better patient management and the mitigation of severe pneumonia.Keywords: severe acute respiratory syndrome coronavirus-2, Omicron, pneumonia, computed tomography, viral load

Chen Yang,1 Jiaxing Lei,1 Ximeng Kang,1 Peipei Zhang,1 Shaohua Zheng,2 Qingqing Li,1 Jiye Zhang1 1School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Qingqing Li; Jiye Zhang, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76 Yanta Westroad, Xi’an, People’s Republic of China, Email liqingqing0217@mail.xjtu.edu.cn; zjy2011@mail.xjtu.edu.cnIntroduction: The effect of traditional treatment for melanoma is quite limited, especially for its recurrence. As the major components of yeast cell wall, chitin and β-glucan exhibit good immune activation effect and are promising candidates for adjuvant. Therefore, melanoma cell membrane (CM) and indocyanine green (ICG) was loaded in a chitin and β-glucan hybrid hydrogel to achieve an enhanced anti-melanoma therapy.Methods: The novel hybrid hydrogel was prepared, and its physicochemical properties were examined. Its effect towards melanoma prevention and treatment was evaluated via a melanoma-bearing mice model.Results: The CM-ICG-hybrid hydrogel was successfully prepared with excellent injectability, self-healing, drug loading, rheological, in vitro and in vivo photothermal stability, and retention properties. It also exhibited good cellular and in vivo safety profiles. In the primary melanoma mice model, it quickly ablated the in-situ melanoma, effectively inhibited the tumor growth, increased the survival rate of melanoma-bearing mice, and increased the level of IFN-γ and TNF-α. In the distal secondary melanoma model, it efficiently prevented the reoccurrence of melanoma and activated the memory T cells. In both models, a synergistic effect of photothermal therapy and immune therapy was found. The hydrogel effectively recruited CD3+ CD4+ T cells and CD3+ CD8+ T cells, inhibited the proliferation of melanoma cells, and induced the apoptosis of melanoma cells.Conclusion: The hybrid hydrogel was successfully prepared, and it showed excellent efficacy towards melanoma prevention and treatment due to its efficient tumor ablation and immune activation capability.Graphical Abstract: Keywords: chitin, β-glucan, hybrid hydrogel, melanoma cell membrane, photo thermotherapy, immunotherapy

Jun Wang,1 Wenjuan Nie,1 Liping Ma,1 Qiang Li,1 Ruixue Geng,2 Wenhui Shi,1 Naihui Chu1 1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 2Tuberculosis Department, The Second Hospital of Hohhot, Hohhot, People’s Republic of ChinaCorrespondence: Naihui Chu; Jun Wang, Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel/Fax +86 108 950 9301, Email chunaihui1994@sina.com; wangjunzt@126.comObjective: Linezolid is increasingly used in the treatment of multidrug-resistant (MDR) M. tuberculosis (TB) with good efficacy; however, its clinical use is limited by intolerable adverse events (AEs). This usually results in dose adjustment or even discontinuation. Contezolid is a new oxazolidinone antibiotic with in vitro antibacterial activity against MDR TB equivalent to linezolid, but its safety and efficacy in MDB TB treatment has not been established.Methods: We conducted a retrospective study on 25 TB patients who received both linezolid and contezolid in Beijing Chest Hospital from January 1, 2022, to January 31, 2023. All patients received linezolid-containing anti-TB regimen first and then switched to contezolid-containing regimens due to the intolerable linezolid-related AEs.Results: Most (68%, 17/25) of the patients were diagnosed with RR-TB or MDR-TB. A total of 30 AEs were reported in these patients. About 26.7% (8/30) of the AEs were Grade 3 (severe) in severity. After switching to contezolid-containing anti-TB regimens for at least 1 month, the linezolid-related AEs were resolved or improved in 90% of the cases. Clinical improvement was observed in all patients after treatment with contezolid-containing regimen, with negative results of sputum culture and/or smear for M. tuberculosis in 84% of the patients.Conclusion: Contezolid can be the first choice instead of linezolid to combine with other anti-TB drugs if necessary. Well-designed clinical trials are required to further confirm the safety and efficacy of contezolid in the treatment of TB patients.Keywords: contezolid, safety, outcome, tuberculosis, linezolid

Jingzhong Ouyang,1,&ast; Zhengzheng Wang,1,&ast; Kun Yuan,2,&ast; Yi Yang,3,4 Yanzhao Zhou,1 Qingjun Li,1 Nanmu Yang,1 Haitao Zhao,5 Hong Zhao,3,4 Jinxue Zhou1 1Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 2School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 3Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Zhao, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100020, People’s Republic of China, Email zhaohong@cicams.ac.cn Jinxue Zhou, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, 450003, People’s Republic of China, Email zhoujx888@126.comPurpose: To evaluate the efficacy and safety of lenvatinib plus programmed death-1 (PD-1) antibody as postoperative adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risks of recurrence.Patients and Methods: A series of 137 patients with HCC at high risks of recurrence who underwent hepatectomy at our hospital between October 2019 and January 2022 were retrospectively analyzed. Recurrence-free survival (RFS), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. Landmark analysis was used to compare short- and long-term RFS. Univariable and multivariable analyses were used to identify prognostic factors, and subgroup analyses were performed according to high risks of recurrence.Results: A total of 85 patients underwent hepatectomy alone and 52 patients received postoperative adjuvant therapy. Compared with the hepatectomy group (HG), RFS was significantly improved in the adjuvant therapy group (ATG) (P < 0.001), but OS was not (P = 0.098). Landmark analysis revealed that RFS within 6 months of the HG was significantly different from that of the ATG (P < 0.001) but not after 6 months (P = 0.486). Multivariable analysis showed that without adjuvant therapy, high Child-Pugh classification, high alpha-fetoprotein levels, microvascular invasion, and satellite lesions were independent risk factors for recurrence within 6 months after hepatectomy. Subgroup analysis revealed that patients with MVI significantly benefited from adjuvant therapy in RFS. But for OS, adjuvant therapy was only significantly effective in patients with single tumor. The most common treatment-related adverse events during adjuvant therapy were hypertension (36.5%), rash or itching (28.8%), diarrhea (23.1%), and fatigue (21.2%).Conclusion: Postoperative adjuvant lenvatinib plus PD-1 antibody significantly improved RFS in patients with HCC at high risks of recurrence with acceptable safeties.Keywords: hepatocellular carcinoma, postoperative adjuvant therapy, lenvatinib, PD-1 antibody, efficacy, safety

Zhimin Shen,1,&ast; Shiping Chen,2,&ast; Yiqiang Duan,1 Juan Yu,3 Dayang Pan,4 Jiaxin Dong,1 Shanglong Wang,1 Qizhe Li,1 Yinlong Xiao,1 Xun Yuan1 1Department of Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang City, People’s Republic of China; 2Department of Orthopedics, The No.1 People’s Hospital of Qingzhen, Qingzhen City, People’s Republic of China; 3The Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang City, People’s Republic of China; 4The 4th People’s Hospital of Guiyang, Guiyang City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiqiang Duan, Department of Orthopedics, The Affiliated Hospital of Guizhou Medical University, No. 28, Guiyijie Road, Guiyang City, Guizhou Province, 550004, People’s Republic of China, Email duanyiqiang0114@163.com Juan Yu, The Affiliated Stomatological Hospital of Guizhou Medical University, No. 9, Beijing Road, Guiyang City, Guizhou Province, 550004, People’s Republic of China, Email 416876483@qq.comObjective: To explore the application value of adjustable skin stretchers for repairing skin wound defects.Methods: Twenty patients with skin defects were included in this study. The largest defect was measured to be 45.4 cm × 13.3 cm (length × width) and the smallest one was 4.4 cm × 3.2 cm (length × width). All patients were subjected to adjustable skin stretchers and the short- and long-term clinical efficacy was evaluated.Results: The wounds of all enrolled patients were healed completely except for one patient with a dorsal foot infection (the patient requested to return to the local county hospital for further treatment), with a total satisfaction of 100%. Postoperative 3-month follow-up showed scar formation, a little local hyperpigmentation, normal skin elasticity, and intact organs of involved cases, thus signifying the significant impact of adjacent joint activities.Conclusion: Adjustable skin stretchers can accurately control the tension on wound margins, breaking the limitation of previous stretchers to provide objective quantitative indicators for clinical application. These stretchers are characterized by high use-value and are worth promoting.Keywords: adjustable skin stretchers, wound-related defects, wound repair

Yonghong Gao,1 Yan Wang,1 Dandan Zhang,2 Tingting Wu,1 Qingwei Li1 1Department of Cardiology, Shanghai Jinshan District Tinglin Hospital, Shanghai, 201505, People’s Republic of China; 2Department of General Practice, Shanghai Jinshan District Tinglin Hospital, Shanghai, 201505, People’s Republic of ChinaCorrespondence: Qingwei Li, Department of Cardiology, Shanghai Jinshan District Tinglin Hospital, Shanghai, 201505, People’s Republic of China, Email tel18930810663@163.comBackground: In the general population of the United States (U.S.), the relationship between dietary inflammatory index (DII) and mortality (all-cause, cardiovascular disease (CVD)-related, and cancer-related) is still unclear. Therefore, in this research, we examined the association of DII with mortality caused by all-cause, CVD-related, and cancer-related causes.Methods: Data from the National Health and Nutrition Examination Survey (NHANES) from 1999– 2018 was used for exploring the link between DII and all-cause, CVD-related, and cancer-related mortality through the use of Cox proportional hazard models and restricted cubic spline model. In addition, subgroup analyses were further performed.Results: The study included 29,013 individuals from the NHANES from 1999 to 2018. The DII scores were nominated as low (T1: − 5.281– 0.724), medium (T2: 0.725– 2.513), and high-grade inflammation (T3: 2.514– 5.795), with T1 serving as the reference group. The linear positive correlation between DII and all-cause and CVD-related mortality was studied using Cox regression analysis. In the full-adjusted model, as compared with the individuals with T1 DII scores, adjusted odds ratios with 95% confidence intervals for all-cause and CVD-related mortality were 1.149 (1.059, 1.247), and 1.186 (1.084, 1.297), as well as 1.197 (1.032, 1.387), and 1.198 (1.019, 1.409), respectively. However, there was no statistical significance between DII and cancer-related mortality. The RCS plot also showed a significant increase in all-cause and CVD-related mortality with increased DII. Nevertheless, as DII scores increased, cancer-related mortality first increased and then decreased.Conclusion: All-cause and CVD-related mortality are linked independently to high DII scores, independently. Further study of the association of DII scores with mortality caused by all-cause, CVD-related, and cancer-related causes is necessary to explore.Keywords: all-cause mortality, cancer-related mortality, cardiovascular disease-related mortality, dietary inflammation index, National Health and Nutrition Examination Survey

Yiran Fu,1 Weishe Zhang,1,2 Qi Wang,1 Caihong Hu,1 Qi Li,3 Jingrui Huang1 1Department of Obstetrics, Xiangya Hospital Central South University, Changsha, People’s Republic of China; 2Hunan Engineering Research Center of Early Life Development and Disease Prevention, Changsha, People’s Republic of China; 3Reproductive Medicine Center, Xiangya Hospital Central South University, Changsha, People’s Republic of ChinaCorrespondence: Jingrui Huang, Department of Obstetrics, Xiangya Hospital Central South University, 87 Xiangya Road, Changsha, 410008, People’s Republic of China, Email jingruihuang@hotmail.com; huangjingrui@csu.edu.cnIntroduction: To evaluate the methodological quality of diagnosis and treatment guidelines/consensus related to ectopic pregnancy.Materials and methods: Use the “Appraisal of Guidelines and Research and Evaluation” (AGREE II) method to evaluate the differences among the guideline/consensus.Results: We appraised 9 clinical practice guidelines for ectopic pregnancy (9 clinical practice guidelines from 5 countries) including the United States, United Kingdom, Ireland, Canada, and China. The guidelines received the highest scores for clarity of presentation (82.72%) and lowest scores for editorial independence (30.56%). The comprehensive recommendations of the 7 guidelines were Grade B, the other 2 guidelines were Grade C.Conclusion: The overall quality of the ectopic pregnancy guidelines had room for improvement. It is recommended to supplement and improve the four fields of “independence”, “rigor”, “participants” and “application”, especially the “independence” and “application” fields.Keywords: guidelines, ectopic pregnancy, pelvic pain, AGREE II, clinical practice

Qingqing Li,1– 3 Ming Gao,4 Yanfang Deng,4 Zongkui Zhou,1– 3 Jing Wang1– 3 1Key Laboratory of Adolescent Cyberpsychology and Behavior (CCNU), Ministry of Education, Wuhan, People’s Republic of China; 2Key Laboratory of Human Development and Mental Health of Hubei Province, School of Psychology, Wuhan, People’s Republic of China; 3School of Psychology, Central China Normal University, Wuhan, People’s Republic of China; 4Beijing Dentons (Yichang) Law Office, Yichang, People’s Republic of ChinaCorrespondence: Jing Wang, School of Psychology, Central China Normal University, LuoYu Road 152, Hongshan Region, Wuhan, People’s Republic of China, Email jingwang888@ccnu.edu.cnIntroduction: Identifying risk and protective factors of aggressive behavior during adolescence is beneficial for the intervention and prevention treatments. Although studies show that attachment quality is closely related to aggression, the underlying psychological mechanisms remain unclear. This study aimed to investigate the links of parental attachment with proactive and reactive aggression and to examine the mediating role of perspective taking and self-control among Chinese adolescents.Methods: A cluster sampling method was used to recruit participants from several high schools located in the central regions of China. A total of 2982 participants (Mage = 17.28, SD = 0.83, range 15~20 years; 1602 girls, 1380 boys) were included in the final analysis.Results: Correlation analysis showed that participants possessing higher attachment security with parents were more likely to report lower levels of proactive and reactive aggression. And, self-control and perspective taking were positively associated with parental attachment, and negatively associated with both types of aggression. Moreover, structural equation models indicated that parental attachment directly, and indirectly predicted proactive and reactive aggression through self-control and perspective taking.Discussion: Overall, this study contributes to a more comprehensive understanding of the explanatory mechanisms that link adolescent-parent attachment and aggression, and suggest that high quality of adolescent-parent interactions may promote adolescents’ self-control and perspectives taking, which further reduces their aggression propensity.Keywords: attachment, aggression, self-control, perspective taking, adolescence

Qirong Li,1,2,&ast; Xinyi Zhang,2,&ast; Qiang Feng,2,&ast; Hengzong Zhou,2,&ast; Chaoyang Ma,3 Chao Lin,4 Dongxu Wang,2 Jianmei Yin1 1Department of Otolaryngology-Head and Neck Surgery, the First Hospital of Jilin University, Changchun, People’s Republic of China; 2Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, People’s Republic of China; 3Hepatology Hospital of Jilin Province, Changchun, People’s Republic of China; 4School of Grain Science and Technology, Jilin Business and Technology College, Changchun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongxu Wang; Jianmei Yin, Email wang_dong_xu@jlu.edu.cn; yinjianmei1985@jlu.edu.cnAbstract: Allergic rhinitis (AR) is a chronic allergic disease of the upper respiratory system that affects approximately 10– 40% of the global population. Due to the large number of plant pollen allergens with obvious seasonal variations, AR is common in China. AR is primarily caused by the abnormal regulation of the immune system. Its pathophysiological mechanism involves a series of immune cells and immune mediators, including cytokines. The present review summarizes the common allergens in China and the complex pathophysiological mechanism of AR. Additionally, host allergen contact, signal transduction, immune cell activation, cytokine release, and a series of inflammatory reactions are described according to their sequence of occurrence.Keywords: allergic rhinitis, host immune response, immunoglobulin E, histamine, inflammation

Bingqing Zhang,&ast; Qiang Li,&ast; Qinglin Xu, Baochao Li, Heng Dong, Yongbin Mou Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongbin Mou; Heng Dong, Nanjing Stomatological Hospital, Medical School of Nanjing University, &num;30 Zhongyang Road, Nanjing, 210008, People’s Republic of China, Email yongbinmou@nju.edu.cn; dongheng90@smail.nju.edu.cnBackground: Inflammatory bowel disease (IBD) is closely related to higher intracellular oxidative stress. Therefore, developing a novel method to scavenge the harmful reactive oxygen species (ROS) and alleviate colon inflammation to treat IBD is a promising strategy.Methods: CeO2@PDA-PEG (CeO2@PP) were synthesized by modifying ceria (CeO2) nanorods with polydopamine (PDA) and polyethylene glycol (PEG). The ROS scavenging ability of CeO2@PP was detected by using flow cytometry and confocal laser scanning microscope (CLSM). The anti-inflammatory ability of CeO2@PP was determined in vitro by treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The biocompatibility of CeO2@PP was evaluated in vivo and in vitro. Moreover, the therapeutic effects of CeO2@PP in vivo were estimated in a dextran sulfate sodium salt (DSS)-induced colitis mouse model.Results: Physicochemical property results demonstrated that PDA and PEG modification endowed CeO2 nanorods with excellent dispersibility and colloidal stability. CeO2@PP maintained superior enzyme-like activity, including superoxide dismutase (SOD) and catalase (CAT), indicating antioxidant ability. Moreover, in vitro results showed that CeO2@PP with PDA promotes LPS-induced RAW 264.7 macrophages into M2-type polarization. In addition, in vitro and in vivo results showed that CeO2@PP have great biocompatibility and biosafety. Animal experiments have shown that CeO2@PP have excellent anti-inflammatory effects against DSS-induced colitis and effectively alleviated intestinal mucosal injury.Conclusion: The nanoplatform CeO2@PP possessed excellent antioxidant and anti-inflammatory properties for scavenging ROS and modulating macrophage polarization, which is beneficial for efficient colitis therapy.Graphical Abstract: Keywords: ceria, PDA, nanozyme, antioxidation, anti-inflammation, macrophage polarization, colitis

Wenyu Zhou,1,&ast; Song Hu,1,2,&ast; Yutong Wu,1,&ast; Huan Xu,1,&ast; Lina Zhu,1 Huimin Deng,1 Sheng Wang,1 Yuanli Chen,1 Huanping Zhou,1 Xin Lv,1 Quanfu Li,1 Hao Yang1 1Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, People’s Republic of China; 2Graduate School, Wannan Medical College, Wuhu, AnHui, 241002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Yang, Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Email yanghaozunyi@sina.com Quanfu Li, Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Email quanfuli185@163.comBackground: Mesenchymal stem cell-derived exosomes (MSC-exosomes) have been found to effectively improve the systemic inflammatory response caused by acute lung injury and acute respiratory distress syndrome (ALI/ARDS), regulate systemic immune disorders, and help injured cells repair. The purpose of this study was to take a holistic view of the current status and trends of MSC-exosomes research in ALI/ARDS.Methods: Bibliometrix, Citespace and VOSviewer software were used for bibliometric analysis of the data. We analysed the world trends, country distribution, institution contribution, most relevant journals and authors, research hotspots, and research hotspots related to Coronavirus Disease 2019 (COVID-19) based on the data collected.Results: China possessed the largest number of publications, while the USA had the highest H-index and the number of citations. Both China and the USA had a high influence in this research field. The largest number of publications in the field of MSC-exosomes and ALI/ARDS were mainly from the University of California system. Stem Cell Research & Therapy published the largest number of papers in this scope. The author with the greatest contribution was LEE JW, and ZHU YG published an article in Stem Cell with the highest local citation score. The most frequent keyword and the latest research hotspot were “NF-κB” and “Coronavirus Disease 2019”. Furthermore, our bibliometric analysis results demonstrated that MSC-exosomes intervention and treatment can effectively alleviate the inflammatory response caused by ALI/ARDS.Conclusion: Our bibliometric study suggested the USA and China have a strong influence in this field. COVID-19-induced ALI/ARDS had become a hot topic of research.Keywords: acute respiratory distress syndrome, mesenchymal stem cells, exosome, bibliometrix, Citespace, VOSviewer

Meng Zhou,&ast; Fang Lu,&ast; Ling Jiang, Chen Chen, Si Chen, Luhan Geng, Rui Sun, Qing Li, Suyan Duan, Bo Zhang, Huijuan Mao, Changying Xing, Yanggang Yuan Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanggang Yuan; Changying Xing, Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, Tel/Fax +86-25-6830-6462, Email ygyuan@njmu.edu.cn; cyxing62@126.comAim: Diabetic kidney disease (DKD) continues to be devastating complication of diabetes mellitus. Immune response and inflammatory reaction play essential roles in the progression of DKD. But the specific mechanism of immune cells, and their act on renal innate cells remains unclear. This article focused on immune cells and their communication with renal innate cells to provide bioinformatic evidence for further understanding the immune mechanism in DKD.Methods: Data were analyzed to evaluate the differentially expressed genes (DEGs) and their pathways in DKD patients and mice. Gene set enrichment analysis (GSEA) was used to explore the immune inflammation-related pathways. CIBERSORT was applied to evaluate the distribution of inflammatory cells in different states. Cell-type DEGs and their enrichment pathways were further explored in podocytes, proximal tubule cells and injured tubule cells. Cellchat was used to reveal the cellular communication between immune cells and renal innate cells in DKD.Results: GO and KEGG analysis showed that DEGs were mainly enriched in immune inflammation-related pathways. Monocytes, M2 macrophages and T cells were significantly increased in DKD samples, especially in renal tubule. ScRNA datasets showed that the immune cells number in DKD were significantly increased. Cell-type DEGs were involved in kidney growth and development. In DKD, the interaction numbers and strength between immune cells and innate cells were significantly increased. VISTANT, SPP1 and IGF signal flow were increased in DKD. SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1-Igf1r receptor ligand pairs were enhanced in DKD, which mediated the communication between immune-inflammatory cells and innate cells.Conclusion: Our study explored the pathogenesis of renal injury promoted by immunoinflammatory in DKD. VISTANT, SPP1, and IGF signaling pathways and SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1- Igf1r receptor ligand pairs might occupy essential place in the occurrence and progress of DKD.Keywords: diabetic kidney disease, immune cells, renal innate cells, bioinformatics

Xiaosu Wang,&ast; Dan Zhang,&ast; Zheng Dai, Jingdan Yu, Qichao Li, Litao Zhang Department of Clinical Laboratory, Wuhan Asia General Hospital, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, 430056, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Litao Zhang, Email dandanzhangnihao@126.comIntroduction: W. confusa has been known to cause various human infections. It is naturally resistant to vancomycin and is difficult to identify using traditional methods, which may lead to misidentification and delay treatment.Case Presentation: We present a case of a 42-year-old male patient with gastrointestinal bleeding and coronary heart disease who developed sepsis caused by Weissella confusa. The patient’s blood cultures showed the presence of gram-positive coccobacilli, later identified as W. confusa through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing revealed that W. confusa had low minimum inhibitory concentrations (MICs) for some drugs (eg, ampicillin) and higher MICs for others (eg, cefotaxime). Empirical treatment with vancomycin was initially started, but after obtaining the identification and susceptibility results, the treatment was switched to meropenem combined with daptomycin, resulting in a successful outcome.Conclusion: Weissella confusa bacteremia is relatively rare, and accurate pathogenic diagnosis is essential for effective clinical treatment.Keywords: Weissella confusa, bacterial identification, 16S rRNA, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Yingji Li,1 Qiang Li,2 Bo Yu,1 Hongyi Mou,3 Xin Yang,3 Dongmei Xia4 1School of Humanities and Management, Yunnan University of Chinese Medicine, Kunming, People’s Republic of China; 2School of Economics and Management, Shanghai Technical Institute of Electronics & Information, Shanghai, People’s Republic of China; 3Faculty of Business & Technology, Stamford International University, Bangkok, Thailand; 4Quality Education Center for College Students, Chongqing Institute of Engineering, Chongqing, People’s Republic of ChinaCorrespondence: Dongmei Xia, Email 00137@cqie.edu.cnPurpose: Although the motives of philanthropy vary from country to country around the world, it is still conducive to building a harmonious society to a certain extent.Methods: It uses partial least squares (PLS) to verify the stability of the model and test the model’s hypotheses to analyze the mechanism of action between perceived class mobility and behavioral intention to give online.Results: It was found that perceived class mobility, philanthropic sentiment, and philanthropic cognition affected online giving intention; perceived class mobility had a significant effect on philanthropic cognition and philanthropic sentiment; philanthropic sentiment and philanthropic cognition mediated the relationship between perceived class mobility and giving behavior intention.Conclusion: The study suggests that nonprofit organizations should stimulate behavioral intentions to give by creating an atmosphere of upward class mobility.Keywords: philanthropy, class mobility, philanthropic perception, giving behavior intention

Xiaoming Yang,1,&ast; Zhongda Liu,1,&ast; Xiaojing Liu,1 Quan Li,1 Hui Huang,1 Rui Li,2 Meiyan He1 1Department of Respiratory and Critical Care Medicine, Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui, 323000, People’s Republic of China; 2Department of Cardiology, Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University for Traditional Chinese Medicine, Lishui, 323000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meiyan He, Department of Respiratory and Critical Care Medicine, Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine, No. 800 Zhongshan Road, Liandu District, Lishui, Zhejiang Province, People’s Republic of China, Tel +8618767861290, Email 452843312@qq.comAbstract: The incidence of Chlamydia psittaci infection has been reported to increase in recent years. The presentation of psittacosis infection varied widely, from none to severe symptoms. Mainly, psittacosis infection presents with pulmonary manifestations. Here, we report the case of a 60-year-old female patient with Chlamydia psittaci pneumonia complicated by myocarditis. After administering antibiotics, the patient recovered from severe atypical pneumonia and myocarditis. In general, Chlamydia psittaci rarely induces myocarditis. Moreover, the optimal therapeutic strategies remain unclear for such cases, especially with a high troponin T level. Metagenomic Next-Generation Sequencing (mNGS) can provide a quick and effective diagnosis of Chlamydia psittaci pneumonia; early intervention (antibiotic therapy and nutritional supplements for myocarditis) favors a good outcome, although complications may worsen the condition. Therefore, more studies are required to help improve understanding of the disease.Keywords: Chlamydia psittaci, pneumonia, myocarditis, metagenomic next-generation sequencing, case report

Kang Huang,1,&ast; Tianyi Ma,1,&ast; Qiang Li,1 Yilei Zhou,2 Ting Qin,1 Zanrui Zhong,1 Shilin Tang,1 Wei Zhang,1 Jianghua Zhong,1 Shijuan Lu1 1Department of Cardiovascular Medicine, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, People’s Republic of China; 2Medical College, Jingchu University of Technology, Jingmen, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shijuan Lu, Department of Cardiovascular Medicine, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, No. 43, Renmin Avenue, Haidian Island, Haikou, Hainan, 570100, People’s Republic of China, Tel/Fax +86-13005013999, Email lushijuan122@163.comBackground: The pathophysiological mechanism of ischemic stroke is complex. Traditional risk factors cannot fully or only partially explain the occurrence and development of IS. Genetic factors are getting more and more attention. Our study aimed to explore the association between CYP4F2 gene polymorphism and susceptibility to IS.Methods: A total of 1322 volunteers were enrolled to perform an association analysis through SNPStats online software. Using FPRP (false-positive report probability) to detect whether the result is a noteworthy finding. The interaction of SNP-SNP in IS risk was assessed by multi-factor dimensionality reduction. Statistical analysis of this study was mainly completed by SPSS 22.0 software.Results: Mutant allele “A” (OR = 1.24) and genotype “AA” (OR = 1.49) or “GA” (OR = 1.26) of CYP4F2-rs2108622 are risk genetic factors for IS. Rs2108622 is significantly associated with an increased risk of IS among subjects who are females, aging > 60 years old, with BMI ≥ 24 kg/m2, and smoking or drinking volunteers. CYP4F2-rs3093106 and -rs3093105 are associated with susceptibility to IS among smoking, drinking subjects, or IS patients complicated with hypertension.Conclusion: CYP4F2-rs2108622, -rs3093106, and -rs3093105 are associated with an increased risk of IS.Keywords: ischemic stroke, susceptibility, CYP4F2, genetic variants, association analysis

Xiaoyi Feng,1,&ast; Huaye Xiao,2,&ast; Yishan Duan,1 Qinxue Li,1 Xuemei Ou1 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Fushun People’s Hospital, Zigong, Sichuan, 643200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemei Ou, Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China, Email ouxuemei@163.comObjective: This study aimed to evaluate the predictive value of neutrophil to lymphocyte ratio (NLR) for poor outcomes within 90-day in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods: A retrospective study including 503 AECOPD patients was performed, and the subjects’ clinical characteristics were collected. Binary logistic regression analysis was used to identify risk factors for 90-day poor outcomes in patients with AECOPD. Receiver-operating characteristic curves (ROC) and areas under the curves (AUC) were used to assess the ability of different biomarkers to predict the risk of 90-day mortality, readmission and re-exacerbation in patients with AECOPD.Results: During the follow-up, 188 patients (38.4%) redeveloped exacerbations, 112 patients (22.9%) were readmitted, and 20 patients (4.1%) died directly resulted from COPD or COPD-related causes. Multivariate analysis demonstrated that age> 72 years (OR: 14.817, 95% CI: 1.561– 140.647), NLR> 14.17 (OR: 9.611, 95% CI: 2.303– 40.113), EOS< 0.15% (OR: 8.621, 95% CI: 3.465– 34.913) and BNP> 2840ng/L (OR: 5.291, 95% CI: 1.367– 20.474) at discharge were independent risk factors for 90-day mortality in AECOPD patients. NLR was the optimal biomarker for predicting 90-day mortality with an AUC of 0.802 (95% CI: 0.631– 0.973). Using 14.17 as the critical value of NLR, the sensitivity was 76.7%, and the specificity was 88.9%. Compared with mortality, NLR had no significant advantage in predicting risk of short-term re-exacerbation (AUC=0.580, 95% CI:0.529– 0.632, p=0.001) and readmission (AUC=0.555, 95% CI:0.497– 0.614, p=0.045), with AUCs less than 0.6. In contrast, the predictive value of EOS (AUC=0.561, 95% CI:0.502– 0.621, p=0.038) was slightly better than NLR in terms of readmission within 90 days. CRP did not serve as a well predictive biomarker for the risk of readmission and re-deterioration (p> 0.05).Conclusion: NLR is of great value in predicting the risk of poor outcomes, especially COPD associated mortality, in hospitalized patients with AECOPD within 90 days after discharge.Keywords: acute exacerbation of chronic obstructive pulmonary disease, neutrophil to lymphocyte ratio, mortality, readmission, eosinophil count, C-reactive protein, biomarker

Jiangping Ye,1 Qiaoyun Li2 1Department of Ophthalmology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Pathology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Jiangping Ye, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, 261 Huansha Road, Hangzhou, People’s Republic of China, Email 18267851205@163.comAbstract: Sebaceous carcinoma (SC) is an uncommon but aggressive malignancy and has a specific anatomic preference for the ocular region, especially the eyelids. However, periocular SC originated from the eyebrow is rare, which may cause poorer outcomes due to a greater likelihood of orbital invasion and excessive tumor volume. In the present case, we exhibited a 68-year-old male presenting with a large solid mass in his right eyebrow region developing in ten months. Based on the patient’s history, clinical conditions, orbital computed tomography (CT) and magnetic resonance imaging (MRI) scan results, a malignant tumor was suspected preliminarily. Excisional biopsy was performed, and the histopathologic examination and immunohistochemistry (IHC) staining of the tumor revealed SC. The patient declined the enlarged surgery recommended next and ended up with death caused by the distant metastasis of SC. The case highlighted the fact that despite its rarity, SC should be considered as a differential diagnosis of tumors located in the eyebrow region and histopathologic evaluation must be performed to reach a definite diagnosis. Ophthalmologists are supposed to have a comprehensive understanding of the clinicopathological characteristics of this disease and help patients accept the appropriate treatments promptly via properly and adequate communication if necessary.Keywords: sebaceous carcinoma, eyebrow, diagnosis, prognosis, case report, SC

Xiaotong Chen, Yanqiu Zhao, Qi Li, Shengjin Fan Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of ChinaCorrespondence: Shengjin Fan, Tel +86-13304641978, Email fansjhmu@163.comPurpose: The prognosis of patients with unfit or relapsed/refractory (R/R) AML remains poor. Venetoclax (VEN) has been shown to exhibit anti-leukemia stem cell activity; however, few studies have been published on the efficacy and safety of VEN combined with both hypomethylating agents (HMAs) and low-dose chemotherapy for patients with unfit or R/R AML.Methods: This study retrospectively analyzed the clinical characteristics, treatment details, safety profile and clinical outcomes of patients with unfit or R/R AML treated with VEN+ HMAs+ half-dose CAG (LDAC, aclarubicin and granulocyte colony-stimulating factor).Results: A total of 24 AML patients were involved in the study, of whom 13 (54.2%) were in the unfit group, and 11 (45.8%) were in the R/R group. FLT3 and IDH (8/24, 33.3%) were the most common gene aberrations. Patients in the R/R group were found to be more likely to carry KIT (5/11, 45.5%) compared with the unfit group (0/13, 0%) (P = 0.006). The ORR observed during the study was 83.3% (20/24; 14 CR, 2CRi, 4PR). In the unfit group, 11/13 (84.6%) patients achieved cCR (10 CR and 1 CRi); while 5/11 (45.5%) R/R patients achieved response (4 CR and 1 CRi). CR was observed in all AML patients with TP53 (5/5), GATA2 (3/3), CEBPA (3/3) and ASXL1 (3/3). The most common adverse events (AEs) during VEN+ HMAs+ half-dose CAG therapy were persistent cytopenias and infections.Conclusion: The results of this study confirm that VEN+ HMAs+ half-dose CAG is associated with promising efficacy (even high-risk molecular patterns) and tolerable safety profile in patients with unfit or R/R AML. Yet, the study involves only a small sample size, which should not be overlooked. As such, further studies on the efficacy of VEN combined with HMAs and half-dose CAG regimen in AML patients are essential.Keywords: acute myeloid leukemia, BCL2 inhibitor, venetoclax, combined chemotherapy

Qixiu Li,1,2 Wenhua Jing,3 Zhen Wei,1,2 Yifan Wang,1,2 Long Sun1,2 1Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2National Health Commission of China (NHC) Key Laboratory of Health Economics and Policy Research (Shandong University), Jinan, Shandong, People’s Republic of China; 3Hospital Service Department, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Long Sun, Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong, 250012, People’s Republic of China, Email sunlong@sdu.edu.cnBackground: Workplace violence (WPV) had always been the focus of attention in all walks of lives, especially in the health fields. Previous studies had shown it adversely affected mental health for healthcare workers. In addition, both sleep quality and physical activity were supported to have impact on mental health. However, the mechanism of sleep quality and physical activity influence the association between WPV and mental health had not been explored, so the purpose of this paper was to explore this mechanistic link among workplace violence, sleep quality, physical activity, and mental health in Chinese health technicians.Methods: Cross-sectional study was conducted in 3 cities of China, totally 3426 valid questionnaires were collected. WPV, physical activity, and social-demographic variables were evaluated. The Pittsburgh Sleep Quality Index and the Kessler Psychological Distress Scale were used to measure sleep quality and mental health. Descriptive analysis, univariate analysis, Pearson correlation, and moderated mediation analysis were used to estimate prevalence of WPV, association between WPV and mental health, and the role of sleep quality and physical activity on association between WPV and mental health.Results: The prevalence of WPV was 52.2% among Chinese health technicians. After controlling social-demographic and work-related variables, sleep quality partially mediated the effect of WPV on mental health (indirect effect=0.829). Physical activity moderated the relationship between WPV and sleep quality (β=0.235, p=0.013), but not find the moderating role between WPV and mental health (β=0.140, p=0.474), and between sleep quality and mental health (β=0.018, p=0.550).Conclusion: The rate of WPV among health technicians remained at an alarming level. Sleep quality and physical activity could mitigate the adverse effect of WPV on mental health. In the future, we could improve sleep quality and encourage health technicians to engage physical activity to decrease the negative effect of WPV on mental health.Keywords: workplace violence, mental health, sleep quality, physical activity

Wang M, Li Q, Yu S, et al. Onco Targets Ther. 2020;13:6661-6673. We, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 2, 3, 4, 6 and 7 with images from other unrelated articles. Specifically, Images for Figure 2B have been duplicated with images for Figure 2B from Feng Y, Xu Y, Gao Y, et al. A novel lncRNA SOX2OT promotes the malignancy of human colorectal cancer by interacting with miR-194-5p/SOX5 axis. Cell Death Dis. 2021;12:499. https://doi.org/10.1038/s41419-021-03756-y; Figure 2D from Shi Z, Zhou L, Zhou Y, et al. Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/β-catenin signaling pathway. BMB Reports. 2022;55(6):299-304; Figures 3c and 3d from Chen Q, Tan L, Jin Z, Liu Y, Zhang Z. Downregulation of CRABP2 Inhibit the Tumorigenesis of Hepatocellular Carcinoma In Vivo and In Vitro. BioMed Research International. 2020;2020:3098327. https://doi.org/10.1155/2020/3098327 and Figure 3e from Yang R, Xing L, Zheng X, et al. RETRACTED ARTICLE: The circRNA circAGFG1 acts as a sponge of miR-195-5p to promote triple-negative breast cancer progression through regulating CCNE1 expression. Mol Cancer. 2019;18:4. https://doi.org/10.1186/s12943-018-0933-7. Images for Figure 2D have been duplicated with images for Figure 1C from Li C, Zhang S, Qiu T, Wang Y, Ricketts DM, Qi C. Upregulation of long non-coding RNA NNT-AS1 promotes osteosarcoma progression by inhibiting the tumor suppressive miR-320a. Cancer Biology & Therapy. 2019;20(4):413-422. https://doi.org/10.1080/15384047.2018.1538612; Figure 2C from Chen H, Pan H, Qian Y, et al. MiR-25-3p promotes the proliferation of triple negative breast cancer by targeting BTG2. Mol Cancer. 2018;17:4. https://doi.org/10.1186/s12943-017-0754-0 and Figure 4C from Chen Z, Xue C. G-Protein-Coupled Receptor 5 (LGR5) Overexpression Activates b-Catenin Signaling in Breast Cancer Cells via Protein Kinase A. Med Sci Monit Basic Res. 2019;25:15-25. https://doi.org/10.12659/MSMBR.912411. Images for Figure 3A have been duplicated with images for Figures 8c and 8d from Liu H, Bi J, Dong W, et al. Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis. Mol Cancer. 2018;17:161. https://doi.org/10.1186/s12943-018-0908-8. Images for Figure 3B have been duplicated with images for Figures 5j and 5k from Wang Y, Zeng X, Wang N, et al. Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma. Mol Cancer. 2018;17:89. https://doi.org/10.1186/s12943-018-0837-6. Images for Figure 4G have been duplicated with images for Figure 5D from Chen Y, Deng Y, Chen L, Huang Z, Yan Y, Huang Z. miR-16-5p Regulates Ferroptosis by Targeting SLC7A11 in Adriamycin-Induced Ferroptosis in Cardiomyocytes. J Inflamm Res. 2023;16:1077-1089. https://doi.org/10.2147/JIR.S393646. Images for Figures 6B and 6D have been duplicated with images for Figures 2e and 2f from Wang Y et al (2018). Images for Figure 7B have been duplicated with images for Figure 3B from Feng Y, Xu Y, Gao Y, et al. A novel lncRNA SOX2OT promotes the malignancy of human colorectal cancer by interacting with miR-194-5p/SOX5 axis. Cell Death Dis. 2021;12:499. https://doi.org/10.1038/s41419-021-03756-y and Figure 7C from Liu Y, Liu R, Yang F, et al. miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1. Mol Cancer. 2017;16:53. https://doi.org/10.1186/s12943-017-0625-8. Images for Figure 7C have been duplicated with images for Figure 1D from Ke B, Wu X, Yang Q, et al. Yi-qi-yang-yin-tian-sui-fang enhances cisplatin-induced tumor eradication and inhibits interleukin-7 reduction in non-small cell lung cancer. Biosci Rep. 2019;39(6):BSR20190052. https://doi.org/10.1042/BSR20190052; Figure 4F from Hao J, Madigan MC, Khatri A, et al. In Vitro and In Vivo Prostate Cancer Metastasis and Chemoresistance Can Be Modulated by Expression of either CD44 or CD147. PLoS ONE. 2012;7(8):e40716. https://doi.org/10.1371/journal.pone.0040716 and Figure 5c from Chen Q, Jiang P, Jia B, et al. RCC2 contributes to tumor invasion and chemoresistance to cisplatin in hepatocellular carcinoma. Human Cell. 2020;33:709–720. https://doi.org/10.1007/s13577-020-00353-7. The authors responded to our queries and explained that a third party was responsible for the experimental work carried out in this study. However, the authors were unable to provide details of the third party or the original data for the study. In addition, the authors did not disclose the involvement of the third party at submission or in the article. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors agree with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Kang Huang,1 Tianyi Ma,1 Qiang Li,1 Zanrui Zhong,1 Ting Qin,1 Yilei Zhou,2 Wei Zhang,1 Shilin Tang,1 Jianghua Zhong,1 Shijuan Lu1 1Department of Cardiology, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, Hainan, 570100, People’s Republic of China; 2Jingchu University of Technology, School of Medicine, Jingmen, Hubei, 448000, People’s Republic of ChinaCorrespondence: Shijuan Lu, Department of Cardiology, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, No. 43, Renmin Avenue, Haidian Island, Haikou, 570100, Hainan, People’s Republic of China, Tel +86-13005013999, Email Lu_shijuan@163.com Jianghua Zhong, Jingchu University of Technology, School of Medicine, No. 33, Xiangshan Avenue, Jingmen, Hubei, 448000, People’s Republic of China, Tel +86-13322003882, Email zhong3882@163.comIntroduction: Ischemic stroke (IS) is a multifactorial and polygenic disease, which is affected by genetic factors. In this study, we explored the role of CYP19A1 single nucleotide polymorphisms (SNPs) in IS in the Chinese population.Methods: 1302 subjects (651 controls and 651 cases) were recruited in this case–control study. Four candidate SNPs (rs28757157 C/T, rs3751592 C/T, rs3751591 G/A, rs59429575 C/T) of CYP19A1 were selected by the 1000 genomes project database. The association between CYP19A1 SNPs and IS risk was assessed using logistic regression analysis with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis further verified the positive results. The interaction of SNP-SNP was analyzed by multi-factor dimensionality reduction (MDR) to predict is risk.Results: In the research, CYP19A1 loci (rs28757157 and rs3751591) were associated with the occurrence of IS. The two variants conferred an increased susceptibility to IS in the subjects aged over 60 years old, smokers and drinkers. Rs28757157 was related to the risk of IS in females, non-smokers and subjects with BMI less than 24, while rs59429575 was related to the risk of IS in males and subjects with BMI greater than 24.Conclusion: The study revealed that there is a significant association between CYP19A1 loci (rs28757157 and rs3751591) and IS risk in the Chinese Han population, providing a theoretical basis for further exploring its specific role in the pathogenesis of IS.Keywords: ischemic stroke, risk, CYP19A1, single nucleotide polymorphisms, case-control study, Chinese Han population

Qi Li,1 Yan Ma2 1Faculty of Marxism, Northeast Normal University, Changchun, Jilin, 130024, People’s Republic of China; 2College of Philosophy and Sociology, Jilin University, Changchun, Jilin, 130024, People’s Republic of ChinaCorrespondence: Yan Ma, Email yanma18@mails.jlu.edu.cnIntroduction: It is urgent to explore and solve the problems in China’s current Marxist psychological education. The main goal of the research is to promote the sinicization innovation of Marxist humanistic theory in colleges and universities.Methods: Combined with Marxist humanist theory, this paper designs a science, technology, engineering, and mathematics teaching mode for cultivating innovative thinking in an attempt to change the way college students cultivate innovative thinking. The research method is to discuss the status, problems, causes, and countermeasures of the sinicization innovation of Marxist humanistic theory in colleges and universities through literature research, logical analysis, and empirical research.Results: The progress and existing problems of college students’ current psychological education logic are summarized based on empirical research. The research results show that the innovation of Marxist humanistic theory in colleges and universities needs to be innovated in terms of theory, method, content, and form and integrated into the development needs and innovation requirements of contemporary Chinese society. The countermeasures implemented include promoting the intersectionality, interdisciplinarity, and innovation of Marxist humanistic theory research in colleges and universities, strengthening the close integration of Marxist humanistic theory education and practice in colleges and universities, and enhancing the effectiveness and orientation of Marxist humanistic theory education in colleges and universities.Discussion: In the context of innovative thinking, the effectiveness of psychological logic education should be further improved through innovative research on the sinicization of Marxist humanistic theory in colleges and universities.Keywords: innovative thinking, Marxism, humanism theory, sinicization innovation, psychological education

Quan Li,1 Rui Bi2 1Department of Clinical Laboratory, Yulin NO.2 Hospital, Yulin City, Shaanxi Province, 719000, People’s Republic of China; 2Department of Obstetrics, Yulin NO.2 Hospital, Yulin City, Shaanxi Province, 719000, People’s Republic of ChinaCorrespondence: Rui Bi, Department of Obstetrics, Yulin NO.2 Hospital, Wenhua South Road, Yulin City, Shaanxi Province, 719000, People’s Republic of China, Tel +86-18992245891, Email birui89@163.comPurpose: It is unknown whether there is an association between 25-hydroxyvitamin D (25(OH)D) level and thyroid disease in postmenopausal women with type 2 diabetes. This study aimed to evaluate the relationship between blood 25(OH)D levels and thyroid function in postmenopausal women with type 2 diabetes mellitus (T2DM).Methods: This cross-sectional study involved Chinese postmenopausal women who presented to our diabetes clinic from March 2021 to May 2022 and were diagnosed with T2DM collected via a convenience sampling method. Blood samples were obtained from each patient to detect serum thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free T3 (FT3), free T4 (FT4), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and 25(OH)D levels. Deficiency was defined as a 25(OH)D

Yueming Zhang,1– 3 Ziyao Guo,1,2 Wen Zhang,3 Qinyuan Li,1,2 Yan Zhao,1,2 Zhili Wang,1,2 Zhengxiu Luo1,2 1Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, People’s Republic of China; 3Department of Respiratory, Xi’an Children’s Hospital, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Zhengxiu Luo, Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China, Email luozhengxiu816@hospital.cqmu.edu.cnObjective: The objective of this study was to conduct a systematic review and meta-analysis to identify the adverse effects of acute PM2.5 exposure on lung function in children.Design: Systematic review and meta-analysis. Setting, participants and measures: Eligible studies analyzing PM2.5 level and lung function in children were screened out. Effect estimates of PM2.5 measurements were quantified using random effect models. Heterogeneity was investigated with Q-test and I2 statistics. We also conducted meta-regression and sensitivity analysis to explore the sources of heterogeneity, such as different countries and asthmatic status. Subgroup analyses were conducted to determine the effects of acute PM2.5 exposure on children of different asthmatic status and in different countries.Results: A total of 11 studies with 4314 participants from Brazil, China and Japan were included finally. A 10 μg/m3 increase of PM2.5 was associated with a 1.74L/min (95% CI: − 2.68, − 0.90) decrease in peak expiratory flow (PEF). Since the asthmatic status and country could partly explain the heterogeneity, we conducted the subgroup analysis. Children with severe asthma were more susceptible to PM2.5 exposure (− 3.11 L/min per 10 μg/m3 increase, 95% CI − 4.54, − 1.67) than healthy children (− 1.61 L/min per 10 μg/m3 increase, 95% CI − 2.34, − 0.91). In the children of China, PEF decreased by 1.54 L/min (95% CI − 2.33, − 0.75) with a 10 μg/m3 increase in PM2.5 exposure. In the children of Japan, PEF decreased by 2.65 L/min (95% CI − 3.82, − 1.48) with a 10 μg/m3 increase of PM2.5 exposure. In contrast, no statistic association was found between every 10 μg/m3 increase of PM2.5 and lung function in children of Brazil (− 0.38 L/min, 95% CI − 0.91, 0.15).Conclusion: Our results demonstrated that the acute PM2.5 exposure exerted adverse impacts on children’s lung function, and children with severe asthma were more susceptible to the increase of PM2.5 exposure. The impacts of acute PM2.5 exposure varied across different countries.Keywords: particulate matter 2.5, PM2.5, children, peak expiratory flow, PEF, acute exposure, meta-analysis

Peiru Si,1 Jiaxing Lei,1 Chen Yang,1 Peipei Zhang,1 Xiaojiao Li,2 Shaohua Zheng,3 Qingqing Li,1 Jiye Zhang1 1School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Biobank, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Anesthesiology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Qingqing Li; Jiye Zhang, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76 Yanta Westroad, Xi’an, People’s Republic of China, Email liqingqing0217@xjtu.edu.cn; zjy2011@xjtu.edu.cnIntroduction: Hepatic ischemia-reperfusion injury (HIRI) is the main reason for liver dysfunction or failure after liver resection and liver transplantation. As excess accumulation of reactive oxygen species (ROS) is the leading factor, ceria nanoparticle, a cyclic reversible antioxidant, is an excellent candidate for HIRI.Methods: Manganese doped mesoporous hollow ceria nanoparticles (MnOx-CeO2 NPs) were prepared, and the physicochemical characteristics, such as particle size, morphology, microstructure, etc. were elucidated. The in vivo safety and liver targeting effect were examined after i.v. injection. The anti-HIRI was determined by a mouse HIRI model.Results: MnOx-CeO2 NPs with 0.40% Mn doped exhibited the strongest ROS-scavenging capability, which may due to the increased specific surface area and surface oxygen concentration. The nanoparticles accumulated in the liver after i.v. injection and exhibited good biocompatibility. In the HIRI mice model, MnOx-CeO2 NPs significantly reduced the serum ALT and AST level, decreased the MDA level and increased the SOD level in the liver, prevent pathological damages in the liver.Conclusion: MnOx-CeO2 NPs were successfully prepared and it could significantly inhibit the HIRI after i.v. injection.Graphical Abstract: Keywords: hepatic ischemia reperfusion injury, Mn-doped mesoporous hollow cerium oxide nanoparticles, oxidative stress

Litao Guo,1 Yu Liu,1 Lei Zhang,1 Qing Li,2 Haibo Qiu,2 Yaling Guo,3 Qindong Shi1 1Department of Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3Department of Infectious Diseases, Xi’an Eighth Hospital, Xi’an, People’s Republic of ChinaCorrespondence: Qindong Shi, Department of Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Road Yanta West, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel +86 029 85323186, Email shiqindong@163.comBackground: Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been widely used in treating patients with coronavirus disease 2019 (COVID-19) with severe respiratory failure. However, there are few reports of the successful treatment of patients with massive airway hemorrhage in severe COVID-19 during VV-ECMO treatment.Methods: We analyzed the treatment process of a patient with a massive airway hemorrhage in severe COVID-19, who underwent prolonged VV-ECMO treatment.Results: A 59-year-old female patient was admitted to the intensive care unit after being confirmed to have severe acute respiratory syndrome coronavirus 2 infection with severe acute respiratory distress syndrome. VV-ECMO, mechanical ventilation, and prone ventilation were administered. Major airway hemorrhage occurred on day 14 of ECMO treatment; conventional management was ineffective. We provided complete VV-ECMO support, discontinued anticoagulation, disconnected the ventilator, clipped the tracheal intubation, and intervened to embolize the descending bronchial arteries. After the airway hemorrhage stopped, we administered cryotherapy under bronchoscopy, low-dose urokinase locally, and bronchoalveolar lavage in the airway to clear the blood clots. The patient’s condition gradually improved; she underwent ECMO weaning and decannulation after 88 days of VV-ECMO treatment, and the membrane oxygenator was changed out four times. She was successfully discharged after 182 days in hospital.Conclusion: Massive airway hemorrhage in patients with severe COVID-19 and treated with ECMO is catastrophic. It is feasible to clamp the tracheal tube with the full support of ECMO. Notably, bronchoscopy with cryotherapy is effective for removing blood clots.Keywords: coronavirus disease 2019, acute respiratory distress syndrome, mechanical ventilation, cryotherapy, airway hemorrhage, extracorporeal membrane oxygenation

Leijuan Gan,1– 3,&ast; Mengran Lang,1– 4,&ast; Xindi Tian,1– 3 Shaohua Ren,1– 3 Guangtao Li,1– 3 Yayue Liu,1– 3 Ruyu Han,1– 3 Kangwei Zhu,1– 3 Huikai Li,1– 3 Qiang Wu,1– 3 Yunlong Cui,1– 3 Wei Zhang,1– 3 Feng Fang,1– 3 Qiang Li,1– 3 Tianqiang Song1– 3 1Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 3Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 4Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang, Hebei, 065001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianqiang Song, Tel +86-022-23340123, Fax +86 022-23537796, Email songtianqiangtj@163.comPurpose: The purpose of this study was to investigate the triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy as a conversion therapy for initially unresectable hepatocellular carcinoma (HCC).Patients and Methods: We retrospectively analyzed data from all HCC patients who underwent lenvatinib plus sintilimab plus arterially-directed therapy at Tianjin Medical University Cancer Hospital between December 2018 and October 2020. Of 98 enrolled patients, 37 patients were classified as potentially resectable. We compared the potentially resectable population (PRP) with the non-potentially resectable population (NPRP). The primary study endpoint was conversion rate, and secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.Results: The baseline characteristics were comparable between populations except for a higher proportion of patients with extrahepatic metastases in the NPRP versus PRP (23/61 [37.7%] vs 3/37 [8.1%], respectively; p=0.003). For PRP, the ORR was 67.6% based on RECIST v1.1 (75.7% based on mRECIST), conversion rate was 40.5% (15/37). Of the 15 patients who underwent surgical resection, three achieved complete pathological remission. The median follow-up for all patients was 28 months (range: 2– 47). For NPRP, the ORR was 22.9% based on RECIST v1.1 (31.1% based on mRECIST), The median PFS for PRP was significantly longer than that of NPRP (25 vs 13 months, p = 0.0025). The median OS for PRP was significantly longer than that of NPRP (not reached VS 21 months, p=0.014). Hypertension was the most common grade ≥ 3 adverse reaction in both PRP and NPRP. No new safety signals were observed for any of the treatments.Conclusion: The triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy can convert potentially unresectable HCC into resectable disease and improve long-term survival.Keywords: lenvatinib, sintilimab, conversion therapy, unresectable hepatocellular carcinoma, TACE, HAIC