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Yameng Song,1,2 Caiyun Yin,2 Ning Kong1 1Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun, People’s Republic of China; 2National Health Commission (NHC) Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Ning Kong, Email kongning@jlu.edu.cnAbstract: Diabetic retinopathy is one of the complications of diabetes mellitus that occurs in the early stages. It is a disease that has a serious impact, and may lead to blindness when the disease progresses to advanced stages. Currently, treatments for diabetic retinopathy are mainly limited to its advanced stages of the disease, being restricted to a single therapeutic mechanism. Stem cells hold the promise of regenerative therapy and have the potential to comprehensively improve diabetic retinopathy. However, direct stem cell therapy carries some risk of carcinogenesis. Exosomes secreted by stem cells have shown a similar overall improvement in disease as stem cells. Exosomes can carry a number of biologically active materials from donor cells to recipient cells or distant organs, regulating intercellular signaling. Exosomes have shown remarkable efficacy in alleviating oxidative stress, inhibiting inflammatory responses, suppressing angiogenesis, reducing apoptosis and protecting neural tissues. Currently, the experimental literature using stem cell exosomes in the treatment of diabetic retinopathy tends to converge on the above experimental results. With this in mind, we have chosen to explore exosomes in depth from a subtle molecular perspective. We will elaborate on this perspective in this paper and propose to advocate exosome therapy as one promising approach for the treatment of diabetic retinopathy to ameliorate the lesions through multiple mechanisms.Keywords: stem cell, exosomes, diabetic retinopathy, versatile mechanisms, treatment

Yongjiao Zhang,1,2 Xiaolei Xuan,2 Diwen Ye,1,2 Dong Liu,2 Yufan Song,2 Fei Gao,2 Sumei Lu2 1School of Medical Laboratory, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Sumei Lu; Fei Gao, Email lsmqianyi@126.com; 448617003@qq.comAbstract: Absent in melanoma 2 (AIM2) is a protein encoded by the AIM2 gene located on human chromosomes, AIM2 can recognize and bind to double stranded DNA (dsDNA), leading to the assembly of the AIM2 inflammasome. The AIM2 inflammasome plays important proinflammation role in many diseases, and can induce pyroptotic cell death. It has also been closely linked to the development and progression of metabolic diseases and can be activated in obesity, diabetes, nonalcoholic fatty liver disease, and atherosclerosis. In this article, we mainly review the role of AIM2 in glucose metabolism, especially in obesity-related disorders of glucose and lipid metabolism, and provide insights to better understand the role of AIM2 in the pathogenesis, and clinical treatment of metabolic disease.Keywords: AIM2, obesity, metabolic diseases, diabetes, glucose metabolism disorders

Chuxiao Zhang, Yuelan Qin, Yangguang Song, Yingying Liu, Xiaodong Zhu Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Department of Radiation OncologyGuangxi Medical University Cancer Hospital, No. 71 hedi Road, Nanning, Guangxi, 530021, People’s Republic of China, Email xdzhu1466@hotmail.comPurpose: There are insufficient data about the optimal treatment for older patients with recurring medium or large hepatocellular carcinoma (HCC). The study intended to assess the effect of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) in an elderly cohort through a retrospective analysis.Methods: From 2011 to 2018, a cohort of individuals (age ≥ 70 years) with recurrent HCC tumors ranging from 3.1 cm to 7 cm underwent either a combination treatment of TACE and MWA (n = 43) or surgical intervention (n = 33). Using the Inverse Probability of Treatment Weighting (IPTW) technique, factors of disease-free survival (DFS), overall survival (OS), and rates of major adverse events were analyzed, retrospectively.Results: The group that underwent surgery had a greater history of alcohol use before treatment (P= 0.001), as well as a higher Barcelona Clinic Liver Cancer (BCLC) stage for the primary tumor before treatment (P= 0.014) and a higher primary tumor location before treatment (P= 0.045). The TACE-MWA group had DFS rates of 86.2%, 68.8%, and 60.4% at 1, 3, and 5 years, while the surgery group had rates of 53.0%, 42.2%, and 25.8% at the same time points. In the TACE-MWA treatment group, survival rates at 1 year, 3 years, and 5 years post-treatment were recorded as 93.0%, 80.8%, and 65.7%, respectively, while in the surgery group, they were 62.7%, 46.9%, and 42.6%. In the univariate analysis using IPTW, the type of treatment was found to have a significant correlation with disease progression (hazard ratio [HR] 0.41, 95% CI 0.20– 0.86, P=0.017). IPTW multivariate analysis showed that treatment modality (HR, 0.35; 95% CI, 0.17 to 0.79; P= 0.011) was the only significant prognostic factor for OS.Conclusion: In elderly patients with recurrent 3.1 cm≤ HCC ≤ 7 cm, TACE-WMA was superior to surgery in the respects of DFS and OS.Keywords: elderly patients, hepatocellular carcinoma, transcatheter arterial chemoembolization, microwave ablation, treatment modality

Kangyi Hu, Haonan Wen, Ting Song, Zhixin Che, Yongjia Song, Min Song Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaCorrespondence: Min Song; Yongjia Song, Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China, Email sm@gszy.edu.cn; syj@gszy.edu.cnAbstract: Long non-coding RNA (LncRNA), with transcripts over 200 nucleotides in length, play critical roles in numerous biological functions and have emerged as significant players in the pathogenesis of osteoarthritis (OA), an inflammatory condition traditionally viewed as a degenerative joint disease. This review comprehensively examines the influence of LncRNA on the inflammatory processes driving OA progression, focusing on their role in regulating gene expression, cellular activities, and inflammatory pathways. Notably, LncRNAs such as MALAT1, H19, and HOTAIR are upregulated in OA and exacerbate the inflammatory milieu by modulating key signaling pathways like NF-κB, TGF-β/SMAD, and Wnt/β-catenin. Conversely, LncRNA like MEG3 and GAS5, which are downregulated in OA, show potential in dampening inflammatory responses and protecting against cartilage degradation by influencing miRNA interactions and cytokine production. By enhancing our understanding of LncRNA’ roles in OA inflammation, we can better leverage them as potential biomarkers for the disease and develop innovative therapeutic strategies for OA management. This paper aims to delineate the mechanisms by which LncRNA influence inflammatory responses in OA and propose them as novel targets for therapeutic intervention.Keywords: osteoarthritis, LncRNA, inflammation, chondrocytes, pro-inflammatory factors

Fanlingzi Shen,1,2,* Yu Song,3,* Yan Qiang,1,* Xiangjin Gao,1 Siyuan Li,2 Rui Zhang,1 Zhongzhi Gao,1 Bin Li,1 Wencheng Jiang,4 Ruiping Wang1,2 1Clinical Research Center, Shanghai Skin Diseases Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Dermatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wencheng Jiang, Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, Medical School, Tongji University, 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Email drjiangwencheng@163.com Ruiping Wang, Clinical Research & Innovation Transformation Center, Shanghai Skin Diseases Hospital, Medical School, Tongji University, 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Email w19830901@126.comPurpose: Tobacco smoking and alcohol drinking are positively associated with psoriasis prevalence and disease severity. Researches focusing on the influence of smoking and drinking on the treatment efficacy of psoriasis are still limited, especially their interaction effect. This study aims to explore the interactive effects of smoking and drinking on the treatment efficacy in psoriasis patients.Patients and Methods: From 2021 to 2022, we recruited 560 patients with psoriasis from Shanghai Skin Diseases Hospital. Demographic and clinical features as well as treatment efficacy were collected through questionnaire interview and physical examination during patient’s hospital visit at week 0, week 4 and week 8. Logistic regression model was used to explore the influence of smoking and drinking on the treatment efficacy in psoriasis patients, and multiplicative and additive interaction models were used to verify the interaction effect of smoking and drinking on the treatment efficacy.Results: The prevalence of smoking and drinking among psoriasis patients was respectively 43.8% and 25.4%, and 19.6% of them with both smoking and drinking. Logistic regression analysis showed that patients with smoking (OR=7.78, 95% CI: 5.26~11.49) and drinking (OR=5.21, 95% CI: 3.29~8.27) had higher risk of experiencing the failure to achieve PASI75 at week 8, even with the adjustment of confounders. Moreover, multiplicative as well as additive model showed that tobacco smoking interacted with alcohol drinking which influenced the treatment efficacy more severely (OR=12.74, 95% CI: 7.16~22.67). The proportion of PASI75 achievement in female patients (OR=19.54) and patients with methotrexate (OR=28.31) and biologics (OR=21.61) were more likely being affected by smoking and drinking.Conclusion: Tobacco smoking and alcohol drinking could increase the failure of PASI75 achievement in patients with psoriasis, individually and interactively. We recommend that dermatologists should educate patients to pay attention to the negative effects of smoking and drinking, encourage them to quit, and thus improve the treatment efficacy.Keywords: psoriasis, tobacco smoking, alcohol drinking, interaction, additive model, multiplicative model

Tianjie Zhang,1 Yan Liu,1 Dongwei Xu,2 Rui Dong,1 Ye Song1 1Department of Ultrasonography, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, People’s Republic of China; 2Department of Critical Care Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ye Song, Email songye@tongji.edu.cnBackground: In recent years, diaphragm ultrasound (DUS) has been used to identify diaphragm dysfunction in the intensive care unit (ICU). However, there are few studies on DUS parameters to evaluate function, normal ranges, and influencing factors in population. The aim of this study is to provide a methodological reference for clinical evaluation of diaphragm function by measuring different DUS parameters in a healthy population.Methods: A descriptive study was conducted 212 (105 males, 107 females) subjects with normal spirometry underwent ultrasound imaging in this study. The diaphragm contraction and motion related parameters and shear wave velocity (SWV) were measured in the supine position. The effects of gender, age, body mass index (BMI) and lifestyle on diaphragm ultrasound parameters were analyzed.Results: The diaphragm thickness at end-expiration (DT-exp) was 0.14 ± 0.05 cm, the diaphragm thickness at end- inspiration (DT-insp) was 0.29± 0.10 cm, with thickening fraction (TF) was 1.11± 0.54. The diaphragm excursion (DE) was 1.68± 0.37cm and diaphragm velocity was 1.45± 0.41 cm/s during calm breathing. During deep breathing, the DE was 5.06± 1.40cm and diaphragm velocity was 3.20± 1.18 cm/s. The Diaphragm shear modulus—longitudinal view were Mean16.72± 4.07kPa, Max25.04± 5.58kPa, Min11.06± 3.88kPa, SD2.56± 0.98. The results of diaphragmatic measurement showed that the DT of males was significantly greater than that of females (P< 0.05), but there was no significant difference in TF. The DT-insp (r=0.155, P= 0.024) and the DT-exp (r=0.252, P=0.000) were positively correlated with age, and the DE during calm breathing was negatively correlated with age (r=− 0.218, P= 0.001) and BMI (r=− 00.280, P= 0.000). The DE (R=0.371, P=0.000) and velocity (R=0.368, P=0.000) during deep breathing were correlated with lifestyle.Conclusion: Our study provides normal reference values of the diaphragm and evaluates the influence of gender, age, body mass index and lifestyle on diaphragmatic morphology.Keywords: diaphragm, reference values, ultrasound, supine position

Furui Zhai, Shanshan Mu, Yinghui Song, Min Zhang, Cui Zhang, Ze Lv Gynecological Clinic, Cangzhou Central Hospital, Cangzhou City, Hebei Province, People’s Republic of ChinaCorrespondence: Furui Zhai, Department of Gynecological Clinic, Cangzhou Central Hospital, 16 Xinhua West Road, Cangzhou City, Hebei Province, People’s Republic of China, Tel +86-0317-2075783, Email zfr860708@126.comPurpose: This study aims to develop a machine learning (ML) model to predict the risk of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN) after loop electrosurgical excision procedure (LEEP), addressing a critical gap in personalized follow-up care.Methods: A retrospective analysis of 532 patients who underwent LEEP for high-grade CIN at Cangzhou Central Hospital (2016– 2020) was conducted. In the final analysis, 99 women (18.6%) were found to have residual or recurrent high-grade CIN (CIN2 or worse) within five years of follow-up. Four feature selection methods identified significant predictors of residual or recurrent CIN. Eight ML algorithms were evaluated using performance metrics such as AUROC, accuracy, sensitivity, specificity, PPV, NPV, F1 score, calibration curve, and decision curve analysis. Fivefold cross-validation optimized and validated the model, and SHAP analysis assessed feature importance.Results: The XGBoost algorithm demonstrated the highest predictive performance with the best AUROC. The optimized model included six key predictors: age, ThinPrep cytologic test (TCT) results, HPV classification, CIN severity, glandular involvement, and margin status. SHAP analysis identified CIN severity and margin status as the most influential predictors. An online prediction tool was developed for real-time risk assessment.Conclusion: This ML-based predictive model for post-LEEP high-grade CIN provides a significant advancement in gynecologic oncology, enhancing personalized patient care and facilitating early intervention and informed clinical decision-making.Keywords: cervical intraepithelial neoplasia, loop electrosurgical excision procedure, residual or recurrent, machine learning, predictive modeling

Zhaorong Gao,1– 3 Zhen Guo,1– 3 Yongbo Song,1– 3 Xiujing Shi,1– 3 Yingzuo Zhao,1– 3 Conghui Liu1– 3 1Qingdao Eye Hospital of Shandong First Medical University, Eye Institute of Shandong First Medical University, Qingdao, People’s Republic of China; 2State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, People’s Republic of China; 3School of Ophthalmology, Shandong First Medical University, Qingdao, People’s Republic of ChinaCorrespondence: Zhen Guo, Qingdao Eye Hospital of Shandong First Medical University, Eye Institute of Shandong First Medical University, 5 Yanerdao Road, Qingdao, Shandong, 266071, People’s Republic of China, Fax +86532 8761 0087, Email guoz@sdfmu.edu.cnPurpose: With girls typically exhibiting higher rates of myopia than boys, however, the mechanisms behind this gender difference remain unclear. This study aims to investigate the gender disparities in the relationship between myopia, sleep duration, physical activity, and BMI.Patients and Methods: A total of 3138 primary and secondary school students were included. Mplus 8.3 was used to perform the multiple mediation analysis.Results: Sleep duration was indicated to directly affect myopia (β=0.273, 95% CI=0.184− 0.356) and through physical activity, BMI, physical activity and BMI three significantly mediation pathways, respectively. In terms of gender, the mediating direct effect of sleep duration on myopia of boys was 66.96%, which is much higher than that of girls’ 50.91%. And the mediating indirect effect of sleep duration on myopia through physical activity and BMI are 32.65% and 12.10% respectively among girls, both of which are significantly higher than that of boys.Conclusion: The study found that there are significant differences in the impact of sleep duration on myopia in children and adolescents of different genders. In this regard, while paying attention to the sleep duration of children and adolescents, special attention should also be paid to the indirect impact of girls’ physical activity and BMI on myopia, and targeted measures should be formulated according to children of different genders to effectively protect the eye health of children and adolescents.Keywords: myopia, children and adolescents, sleep duration, physical activity, BMI, gender difference

Yanyan Song, Bin Zhang, Xudong Liu Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Xudong Liu, Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqnfective shoingDistrict, Yinchuan, 750004, People’s Republic of China, Tel +869516743014, Fax +86 0951-6744302, Email xudong669@163.comObjective: To summarize the experience of surgical treatment and perioperative management of a case of infective endocarditis with aortic valve damage in a child with congenital heart disease.Methods: We retrospectively analyzed the treatment of a pediatric patient with infective endocarditis combined with aortic valve damage, who was admitted to the Department of Cardiovascular Surgery of our hospital in Yinchuan in March 2024. We summarize the case data and present a literature review.Results: The child recovered well after surgery, with echocardiographic re-examination, mild regurgitation of the aortic valve, and no recurrence of endocarditis. She recovered and was discharged from hospital.Conclusion: The surgical treatment of infective endocarditis in children has achieved satisfactory results, and the timing of and indications for surgery are very important to achieve the therapeutic effect.Keywords: infective endocarditis, congenital heart disease, cardiac surgical procedures, child

Xinchao Jiang,1,&ast; Yinyin Guo,2,&ast; Mei Fang,1 Xin Wang,3 Biao Zhang,4 Yi Song,1 Jianxue Qian1 1Department of Pain Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of China; 2Department of Oncology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of China; 3Department of Nephrology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of China; 4Department of Intensive Care, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianxue Qian; Yi Song, Department of Pain Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 39 Xiashatang Road, Wuzhong District, Suzhou, Jiangsu, People’s Republic of China, Tel/Fax +86 0512-69388313 ; +86 0512-69388412, Email szxqjx@126.com; 376063583@qq.comObjective: Knee osteoarthritis (KOA) is a chronic condition characterized by persistent pain that can lead to severe disability. In this study, we primarily investigated the analgesic effect of Huojing decoction on MIA-induced knee arthritis.Methods: The network pharmacology method was employed to acquire target information of Huojing decoction and KOA. MIA was intratibially injected to induce KOA pain in rats. Huojing decoction was then administered once daily via intragastric administration for 14 days. Pain level was assessed by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The levels of inflammatory cytokines were determined by ELISA and PCR. TRPV1 and CGRP were detected through immunohistochemistry. The protein expression of TrkA, MKK3/6 and p38 was assessed by Western blot.Results: Mechanical allodynia and thermal hyperalgesia were observed in KOA rats. The expression levels of inflammatory cytokines were significantly decreased after Huojing decoction infusion of KOA rats. TRPV1 and CGRP were reduced with treatment. Furthermore, the protein expressions of TrkA, MKK3/6 and p38 in the DRG of rats were significantly decreased.Conclusion: Our data suggested that Huojing decoction can alleviate inflammation in KOA pain rats. Additionally, it can inhibit the expression of TrKA, MKK3/6 and p38 signaling pathways, indicating its analgesic effect on KOA pain rats. Keywords: huojing decoction, analgesic effect, knee osteoarthritis, dorsal root ganglion, TrkA/MKK3/6/p38 pathway

Zhuoran Li,1,&ast; Yirui Zhai,1,&ast; Fan Wu,2,&ast; Dayong Cao,2,&ast; Feng Ye,3,&ast; Yan Song,4 Shulian Wang,1 Yueping Liu,1 Yongwen Song,1 Yuan Tang,1 Hao Jing,1 Hui Fang,1 Shunan Qi,1 Ningning Lu,1 Ye-Xiong Li,1 Jianxiong Wu,2 Bo Chen1 1State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 2Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 3Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 4Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Chen, State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China, Tel +86-10-87788280, Email chenboo@outlook.com Jianxiong Wu, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China, Tel +86-10-87781700, Email Dr_wujx@163.comPurpose: This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies.Patients and Methods: Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30– 65 Gy for planning target volume and 40– 65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded.Results: Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level > 1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588– 20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027– 0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up.Conclusion: Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.Keywords: liver cancer, immunotherapy, systemic therapy, radiation therapy

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high risk of recurrence and metastasis. Regular surveillance through physical exams and imaging studies is crucial for the timely detection of recurrences. MCC patients who produce antibodies to the Merkel cell polyomavirus oncoprotein may benefit from antibody testing in addition to routine imaging surveillance for the early detection of disease recurrence. The clinically available Anti MERKel cell panel (AMERK) is a sensitive tumor marker for Merkel cell polyomavirus positive MCC.Although AMERK is highly sensitive, imaging remains necessary to confirm the location of disease recurrence. MCC exhibits characteristic imaging features, making appropriate imaging modalities, and interpretation important for detection.We present 3 representative patient cases that highlight effective utilization of the AMERK test in addition to imaging for the early detection of MCC recurrence. The rise in the AMERK titer may occur before the disease reaches detectable size on computed tomography scans. Positron emission tomography (PET)-CT can serve as an alternative modality for the early detection of disease. Even subtle abnormalities in 18F-FDG uptake may be significant if accompanied by an increased AMERK titer. Alternative imaging modalities, such as 68Ga-DOTATATE PET-CT and magnetic resonance imaging, can be useful in revealing clinically occult disease in MCC patients.In summary, the AMERK antibody test, alongside imaging, enhances sensitivity in detecting recurrence. By combining these strategies of blood test and imaging, healthcare professionals can identify early signs of MCC recurrence, leading to prompt interventions and improved patient outcomes.

Liping Feng,1,&ast; Wencong He,2,&ast; Zexuan Song,3,&ast; Bing Zhao,3 Chong Teng,3 Eryong Liu,3 Hanfang Zhu,1 Shaojun Pei,4 Lina Liu,5 Yuanyuan Song,3 Yang Zheng,3 Xiangyi Liu,2 Yanlin Zhao,3 Xichao Ou3 1Department of Microbiology, Hinggan League Center for Disease Control and Prevention, Ulanhot, 137499, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, 100176, People’s Republic of China; 3National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for Tuberculosis Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 4School of Public Health, Peking University, Beijing, 100191, People’s Republic of China; 5Blood Transfusion Department, Hinggan League People’s Hospital, Ulanhot, 137400, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xichao Ou; Yanlin Zhao, Email ouxc@chinacdc.cn; zhaoyl@chinacdc.cnBackground: Tuberculosis remains a major public health concern in China, with varying prevalence and drug resistance profiles across regions. This study explores the genetic diversity and drug-resistant profiles of MTB strains in Hinggan League, a high TB burden in Inner Mongolia, China.Methods: This population-based retrospective study, encompassing all culture-positive TB cases from Jun. 2021 to Jun. 2023 in Hinggan League. Drug resistant profiles and genetic diversity of MTB strains were assessed using phenotypic drug susceptibility testing and whole-genome sequencing. Risk factors associated with drug resistance were analyzed using univariate and multivariate logistic regression models.Results: A total of 211 MTB strains were recovered successfully and included into final analysis. Lineage 2.2.1 (88.6%, 187/211) was the dominant sub-lineage, followed by lineage 4.5 (7.1%, 15/211) and lineage 4.4 (4.3%, 9/211). MTB strains exhibited the highest resistance rates to isoniazid (16.1%, 34/211), followed by rifampicin (10.0, 21/211). In addition, the MTB strains also showed relatively high rates of resistance against new and repurposed anti-TB drugs, with resistant rates of 2.4% (5/211) to delamanid and 1.9% (4/211) to bedaquiline. Overall, 25.6% (54/211) of MTB strains were DR-TB, and 14 MTB strains met the definition of MDR-TB, including 7 strains of simple-MDR-TB, 5 of pre-XDR-TB, and 2 of XDR-TB. Genetic analysis revealed that the dominant mutations of isoniazid-, rifampin-, ethambutol-, levofloxacin-/moxifloxacin-, and ethionamide- resistance were katG_Ser315Thr(46.4%), rpoB_Ser450Leu (47.4%), embB_Met306Val (25.0%), gyrA_Asp94Ala (40.0%), and fabG1_c15t (42.9%), respectively. Previously treated patients (AOR = 2.015, 95% CI: 1.052– 4.210) and male patients (AOR = 3.858, 95% CI: 1.416– 10.511) were identified as independent risk factors associated with DR-TB.Conclusion: Our study offers crucial insights into the genetic diversity and drug-resistant profiles of TB strains circulating in Hinggan League. These findings are valuable for DR-TB surveillance and for guiding treatment regimens and public health interventions in the region.Keywords: Mycobacterium tuberculosis, drug resistance, genetic diversity, whole-genome sequencing

Yuan Gao,1– 3,&ast; Ce Zong,1,&ast; Ying Yao,4 Haixu Zhao,5 Yuan Song,4 Ke Zhang,1 Hongxun Yang,1 Hongbing Liu,1 Yunchao Wang,1 Yusheng Li,1– 3 Jing Yang,1– 3 Bo Song,1– 3 Yuming Xu1– 3 1Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, People’s Republic of China; 3Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 4School of Health and Nursing, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5School of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuming Xu, Department of Neurology, the First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, Henan Province, People’s Republic of China, 450052, Tel/Fax +86 13903711125, Email xuyuming@zzu.edu.cnPurpose: We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients.Patients and Methods: Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients.Results: In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0– 53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043– 1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063– 1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06– 1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05– 1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age.Conclusion: Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.Keywords: cerebral small vessel disease, incident stroke, fibrinogen-to-albumin ratio, inflammation

Yamei Bai,&ast; Yuqing Chen,&ast; Meng Tian, Jiaojiao Gao, Yulei Song, Xueqing Zhang, Haiyan Yin, Guihua Xu School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guihua Xu, School of Nursing, Nanjing University of Chinese Medicine, No. 138, Xianlin Avenue, Qixia District, Nanjing, Jiangsu Province, 210023, People’s Republic of China, Tel +86-153-6513-2927, Email 7115@njucm.edu.cnPurpose: Social isolation and depression have an impact on cognitive frailty. However, the underlying mechanisms between these variables have not been well defined. This study aims to investigate the mediating role of depressive symptoms in the association between social isolation and cognitive frailty among older adults in China.Methods: From Mar 2023 to Aug 2023, a cross-sectional study was conducted with 496 community-dwelling older adults aged ≥ 60 years in Nanjing, Jiangsu Province, China. Demographic information was collected using the General Information Questionnaire. The Lubben Social Network Scale-6 (LSNS-6), Geriatric Depression Scale 15-item (GDS-15), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR), and FRAIL scale were used for the questionnaire survey. Multiple linear regression and binary logistic regression were utilized to explore the associations among social isolation, depressive symptoms, and cognitive frailty, and Bootstrap analysis was used to explore the mediating role of depressive symptoms in social isolation and cognitive frailty.Results: Linear regression results revealed that social isolation was positively associated with depressive symptoms (β = 0.873, p < 0.001). Logistic regression analysis showed that social isolation (OR = 1.769, 95% CI = 1.018~3.075) and depressive symptoms (OR = 1.227, 95% CI = 1.108~1.357) were significantly associated with cognitive frailty. Mediation analysis demonstrated that depressive symptoms significantly mediated the relationship between social isolation and cognitive frailty, with an indirect effect of 0.027 (95% CI = 0.003~0.051), and the mediating effect accounted for 23.6% of the total effect.Conclusion: Social isolation is associated with cognitive frailty in community-dwelling older adults, and depressive symptoms partially mediate the effect between social isolation and cognitive frailty. Active promotion of social integration among older individuals is recommended to enhance their mental health, reduce the incidence of cognitive frailty, and foster active aging.Keywords: cognitive frailty, social isolation, depressive symptoms, older adults

Huina Gao,1,* Yijun Song,2,* Kun Liu,1,* Xinyuan Lu,3 Jiacheng Shen,2 Sulan Wei,2 Hongni Jiang,1,2 Nuo Xu2 1Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nuo Xu, Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Email xu.nuo@zs-hospital.sh.cn; Hongni Jiang, Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, 668 Jinhu Road, Xiamen, 361015, People’s Republic of China, Email jiang.hongni@zs-hospital.sh.cnPurpose: Cigarette smoking is the most recognized risk factor of chronic obstructive pulmonary disease (COPD) in China. However, there are no studies analyzing the impact of different smoking behaviors on pulmonary function and pulmonary hypertension (PH) among Chinese male patients with COPD.Patients and Methods: Chinese male smokers with COPD performed pulmonary function tests. Clinical characteristics, smoking behavior features, spirometry and echocardiographic results were compared between the two groups stratified by initial smoking age (18 years old) or complicated PH.Results: The early-smoking group had more respiratory symptoms, more severe smoking behavior, worse pulmonary function with lower FEV1%pre (38.5% vs 70.2%) and FEV1/FVC% (47.5% vs 63.8%), and higher systolic pulmonary artery pressure (sPAP: 38.6 vs 33.9 mmHg) than the late-smoking group. Initiating smoking before adulthood was an independently contributing factor of ventilatory dysfunction and Global Initiative for Obstructive Lung Disease (GOLD) stage escalation. It also had a significant interaction with long smoking duration (≥ 30 years), characterized by markedly decreased lung volumes (VC%pre: 64.0% vs 84.5%), impaired diffusing capacity (DLCO%pre: 58.0% vs 76.8%) and severe emphysema (RV/TLC%pre: 145.2% vs 130.2%). COPD patients complicated with PH exhibited worse ventilatory function (FEV1%pre: 43.2% vs 56.2%), impaired diffusion capacity (DLCO%pre: 56.7% vs 77.1%) and decreased lung volume (VC%pre: 67.67% vs 75.38%). Both severe smoking behaviors and impaired pulmonary function had close correlations with sPAP.Conclusion: The early-smoking group exhibited predominantly ventilation dysfunction and had complex interactions with long smoking duration to further affect lung volume and diffusion capacity. Different smoking behaviors influenced variations of pulmonary dysfunction and comorbid PH in patients with COPD.Keywords: chronic obstructive pulmonary disease, pulmonary function, smoking behavior, initial smoking age, pulmonary hypertension

Yue Song,1,&ast; Qing-Qing Dong,2,&ast; Yi-Ke Ni,3 Xiao-Ling Xu,3 Chao-Xiang Chen,3 Wei Chen2 1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, People’s Republic of China; 2ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 3Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang Province, 310015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Ling Xu; Chao-Xiang Chen, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren Street, Hangzhou, 310015, People’s Republic of China, Email ziyao1988@zju.edu.cn; ccx@zjsru.edu.cnAbstract: Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have the capability to induce specific protein degradation. While playing a revolutionary role in effectively degrading the protein of interest (POI), PROTACs encounter certain limitations that impede their clinical translation. These limitations encompass off-target effects, inadequate cell membrane permeability, and the hook effect. The advent of nanotechnology presents a promising avenue to surmount the challenges associated with conventional PROTACs. The utilization of nano-proteolysis targeting chimeras (nano-PROTACs) holds the potential to enhance specific tissue accumulation, augment membrane permeability, and enable controlled release. Consequently, this approach has the capacity to significantly enhance the controllable degradation of target proteins. Additionally, they enable a synergistic effect by combining with other therapeutic strategies. This review comprehensively summarizes the structural basis, advantages, and limitations of PROTACs. Furthermore, it highlights the latest advancements in nanosystems engineered for delivering PROTACs, as well as the development of nano-sized PROTACs employing nanocarriers as linkers. Moreover, it delves into the underlying principles of nanotechnology tailored specifically for PROTACs, alongside the current prospects of clinical research. In conclusion, the integration of nanotechnology into PROTACs harbors vast potential in enhancing the anti-tumor treatment response and expediting clinical translation. Keywords: Proteolysis-targeting chimeras, nanotechnology, delivery, linker, designing principles

Kongzhi Yang, Yaqin Song, Yingjie Su, Changluo Li, Ning Ding Department of Emergency Medicine, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Ning Ding, Department of Emergency Medicine, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, No. 161 Shaoshan South Road, Changsha, Hunan, 410004, People’s Republic of China, Tel + (86)731-8566-7935, Email doctordingning@sina.com; doctordingning@163.comObjective: The purpose of this study is to establishment and validation of an early predictive model for severe acute pancreatitis (SAP).Methods: From January 2015 to August 2022, 2986 AP patients admitted to Changsha Central Hospital were enrolled in this study. They were randomly divided into a modeling group (n = 2112) and a validation group (n = 874). In the modeling group, identify risk factors through logistic regression models and draw column charts. Use internal validation method to verify the accuracy of column chart prediction. Apply calibration curves to evaluate the consistency between nomograms and ideal observations. Draw a DCA curve to evaluate the net benefits of the prediction model.Results: Nine variables including respiratory rate, heart rate, WBC, PDW, PT, SCR, AMY, CK, and TG are the risk factors for SAP. The column chart risk prediction model which was constructed based on these 9 independent factors has high prediction accuracy (modeling group AUC = 0.788, validation group AUC = 7.789). The calibration curve analysis shows that the prediction probabilities of the modeling and validation groups are consistent with the observation probabilities. By drawing a DCA curve, it shows that the model has a wide threshold range (0.01– 0.88).Conclusion: The study developed an intuitive nomogram containing readily available laboratory parameters to predict the incidence rate of SAP.Keywords: acute pancreatitis, severe, risk factors, predictive model, nomogram

Rui Zhou,1,2,&ast; Lijuan Fu,2,&ast; Shu Liu,2,&ast; Sanjie Gao,2 Zhifu Zhao,2 Wencai Jiang,2 Li Liu,2 Weiqiao Ren,2 Dongmei Xiang,2 Xing You,2 Chunyong Tang,2 Yukai Zhou,2 Yanqing Song,2 Juan Xie,2 Li Xie,2 Ru Yu,2 Xianjie Zhang,2 Dan Zhou,2 Jia Han,2 Leqiang Xia,2 Lize Xiong1 1Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Clinical Research Center for Anesthesiology and Perioperative Medicine, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 2Department of Anesthesiology, Deyang People’s Hospital, Deyang, 618000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leqiang Xia, Department of Anesthesiology, Deyang People’s Hospital, No. 173, Section 1, North Taishan Road, Deyang, Sichuan, 618000, People’s Republic of China, Tel +8613547098458, Email xialq123184@163.com Lize Xiong, Shanghai Fourth People’s Hospital, No. 1279, Sanmen Road, Shanghai, 200434, People’s Republic of China, Tel +86-21-55603002, Fax +86-21-56660851, Email mzkxlz@126.com; lizexiong@tongji.edu.cnPurpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy.Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected.Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups.Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.Keywords: propofol, ciprofol, remimazolam, endoscopic sedation, dreaming

Caizhi Sun,1,2,&ast; Yongpeng Xie,1,&ast; Chenchen Zhu,2 Lei Guo,2 Jingjing Wei,2 Bowen Xu,2 Yang Song,2 Haidong Qin,2 Xiaomin Li1 1Department of Emergency Medicine, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang City, Lianyungang, Jiangsu, 222000, People’s Republic of China; 2Department of Emergency Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing City, Jiangsu Province, 210006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaomin Li, Department of Emergency Medicine, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang City, 182 Tongguan North Road, Haizhou District, Lianyungang City, Jiangsu Province, People’s Republic of China, Email lyglxmsj@163.com Haidong Qin, Department of Emergency Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing City, Jiangsu Province, People’s Republic of China, Tel/Fax +8602552271264, Email icuqhd@163.comBackground: To date, there are no studies regarding the Mrp 8/14 in predicting the occurrence of acute respiratory distress syndrome (ARDS) induced by sepsis. Thus, the objective of this study was to investigate the expression of Myeloid-related proteins 8 and 14 (Mrp 8/14) and its role in ARDS induced by sepsis.Methods: A total of 168 septic patients were enrolled in the observational study. The baseline information and clinical outcomes were obtained retrospectively. Serum Mrp 8/14 level was determined by enzyme linked immunosorbent assay (ELISA). The patients were categorized into sepsis and ARDS group based on whether they developed ARDS during the intensive care unit (ICU) hospitalization.Results: There was significant difference in the level of Mrp 8/14 between the sepsis group and ARDS groups (P < 0.05). Mrp 8/14 correlated positively with procalcitonin (PCT), interleukin-6 (IL-6), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score on day 1, mechanical ventilation time, length of ICU stay and hospitalization expenses in ICU (all P < 0.05). Logistic regression analysis showed Mrp 8/14 was the independent factor for forecasting the occurrence of sepsis- induced ARDS (P < 0.05). The areas under receiver operating characteristic curves for Mrp 8/14 were higher than that of PCT, APACHE II score and SOFA score on day 1 (P < 0.05).Conclusion: The serum Mrp 8/14 level at admission may be a potential marker for predicting the occurrence of ARDS induced by sepsis. Early detection of serum Mrp 8/14 could help clinicians to identify and evaluate the severity of ARDS induced by sepsis.Keywords: sepsis, acute respiratory distress syndrome, Mrp 8/14, inflammation, intensive care unit

Zhi Yang,1 Yao Song,1 Bangtao Chen,2 Fei Hao1 1Department of Dermatology, Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, People’s Republic of China; 2Department of Dermatology, Chongqing University Three Gorges Hospital, School of Medicine, Chongqing University, Chongqing, 404100, People’s Republic of ChinaCorrespondence: Bangtao Chen; Fei Hao, Email medisci@163.com; haofei62@163.comObjective: To analyze the associations of the gut and circulating microbiota with circulating vitamin D3 (VD3), type I interferon (IFNI), systemic inflammation, and clinical profiles in chronic spontaneous urticaria (CSU) patients.Methods: A total of 36 CSU patients with VD3 insufficiency (VDI; serum 25(OH)VD3 < 30 ng/mL) and 36 sex-, age-, and body mass index–matched CSU patients with non-VDI were enrolled. Fecal and serum bacteria were identified through 16S rRNA sequencing, and serum 25(OH)VD3 and inflammation biomarkers were assessed using ELISA kits. IFNI response was determined by measuring the stimulatory activity of serum on IFNI-stimulated response element in HEK293 cells in vitro with luciferase assays.Results: Higher urticarial activity score over 7 days (UAS7), higher frequency of levocetirizine resistance, and more severe proinflammation but weaker IFNI response were observed in VDI than non-VDI patients (all P< 0.05). IFNI response was strongly positively associated with serum 25(OH)VD3 level in both groups (P< 0.001). Compared to non-VDI patients, abundance of the fecal genera Prevotella 9, Escherichia–Shigella, and Klebsiella was significantly increased, while Bacteroides, Faecalibacterium, and Agathobacter were remarkably reduced in VDI patients (all P< 0.05). Burkholderia–Caballeronia–Paraburkholderia (40.95%), Acinetobacter (3.05%), and Aquabacterium (2.37%) were the top three bacteria in sera from VDI patients. Both serum 25(OH)VD3 level and IFNI response were positively associated with fecal Bacteroides in the two groups (P< 0.05). In non-VDI patients, there were moderately positive associations between IFNI response and fecal Lachnoclostridium, unclassified_f__Lachnospiraceae, and Phascolarctobacterium and between serum 25(OH)VD3 level and fecal Lachnoclostridium (all P< 0.01). Circulating microbiota in VDI patients was closely related only to proinflammation and UAS7 (both P< 0.05).Conclusion: Changes in gut but not circulating microbiota composition are associated with serum 25(OH)VD3 insufficiency and impaired IFNI homeostasis, which points to greater disease severity (UAS7) and systemic proinflammation in CSU patients.Keywords: chronic spontaneous urticaria, microbiota, vitamin D3, type I interferon, inflammation

Souha H Youssef,1 Alka Garg,2 Yunmei Song,1 Nicole E Wylie,3 Sanjay Garg1 1Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia; 2SA Pharmacy, Women’s and Children’s Hospital, Adelaide, SA, Australia; 3Department of Paediatric Anaesthesia, Women’s and Children’s Hospital, Adelaide, SA, AustraliaCorrespondence: Sanjay Garg, University of South Australia, Adelaide, SA, 5000, Australia, Tel +618 8302 1575, Email sanjay.garg@unisa.edu.auPurpose: Co-administering multiple intravenous (IV) agents via Y-connectors is a common practice in hospitalised and fasting surgical patients. However, there is a lack of reliable data confirming the physical compatibility of some combinations including IV oxycodone, a drug that is gaining increasing popularity in the perioperative period. Concern regarding physical drug incompatibilities precludes concurrent coadministration with other common drugs through a single lumen. This can result in the cessation of infusions to allow the administration of other medications, resulting in exacerbation of acute pain. This study aims to evaluate the physical compatibility of IV oxycodone with some commonly co-administered drugs and IV fluids.Methods: Mixtures of oxycodone (1mg.mL− 1) and the tested drugs and IV fluids were prepared in a ratio of 1:1. The mixtures were examined at 0 and 60 minutes from mixing and assessed using the European Conference Consensus Standards. This involved visual inspection (precipitation, turbidity, colour change, gas formation), spectrophotometry, and pH change. The tested drugs included ketamine, tramadol, clonidine, vancomycin, piperacillin/tazobactam, dexmedetomidine, cefotaxime, gentamicin, and paracetamol. In addition, the commonly used IV fluids tested included glucose 5% + sodium chloride 0.9% + 60 mmol potassium chloride, plasmalyte + dextrose 5%;plasmalyte + dextrose 5% + 55 mmol potassium chloride, plasmalyte + dextrose 5% + 55mmol potassium acetate, plasmalyte + dextrose 5% + 55mmol potassium dihydrogen phosphate, Hartmann’s solution, Standard pediatric Total Parenteral Nutrition (TPN) 20/100 and TPN 25/150.Results: IV oxycodone (1 mg.mL− 1) showed no visual changes; no spectrophotometric absorption variability at 350, 410, or 550nm; and no pH changes of > 0.5 at 0 or 60 minutes with any of the tested drugs or fluids in the concentrations tested.Conclusion: According to European Consensus Conference Standards, IV Oxycodone at 1 mg.mL− 1 is physically compatible in a ratio of 1:1 v/v with all investigated drugs and fluids tested for at least 60 minutes. Keywords: analgesia, physical compatibility, co-administration, intravenous fluid, oxycodone, Y-connector

Minghao Gu,1,2 SenSen Lv,1 Yihui Song,3 Hong Wang,4 Xingyu Zhang,5 Jing Liu,1 Deshun Liu,1 Xiudi Han,1 Xuedong Liu1 1Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, Qingdao, 266011, People’s Republic of China; 2School of Medicine, Qingdao University, Qingdao, 266071, People’s Republic of China; 3Department of Neurology, Weihai Municipal Hospital, Weihai, 264200, People’s Republic of China; 4Hospital-Acquired Infection Control Department, Qingdao Municipal Hospital, Qingdao, 266011, People’s Republic of China; 5Human Resources Department, Qingdao Municipal Hospital, Qingdao, 266011, People’s Republic of ChinaCorrespondence: Xuedong Liu; Xiudi Han, Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, Qingdao, 266011, People’s Republic of China, Email xuedongliu0607@163.com; hanxiudi@163.comPurpose: To investigate the clinical value of serum lysophosphatidylcholine (LPC) as a predictive biomarker for determining disease severity and mortality risk in hospitalized elderly patients with community-acquired pneumonia (CAP).Methods: This prospective, single-center study enrolled 208 elderly patients, including 67 patients with severe CAP (SCAP) and 141 with non-SCAP between November 1st, 2020, and November 30th, 2021 at the Qingdao Municipal Hospital, Shandong Province, China. The demographic and clinical parameters were recorded for all the included patients. Serum LPC levels were measured on day 1 and 6 after admission using ELISA. Propensity score matching (PSM) was used to balance the baseline variables between SCAP and non-SCAP patient groups. Receiver operative characteristic (ROC) curve analysis was used to compare the predictive performances of LPC and other clinical parameters in discriminating between SCAP and non-SCAP patients and determining the 30-day mortality risk of the hospitalized CAP patients. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors associated with SCAP. Cox proportional hazard regression analysis was used to determine if serum LPC was an independent risk factor for the 30-day mortality of CAP patients.Results: The serum LPC levels at admission were significantly higher in the non-SCAP patients than in the SCAP patients (P = 0.011). Serum LPC level < 24.36 ng/mL, and PSI score were independent risk factors for the 30-day mortality in the elderly patients with CAP. The risk of 30-day mortality in the elderly CAP patients with low serum LPC levels (< 24.36ng/mL) was > 5-fold higher than in the patients with high serum LPC levels (≥ 24.36ng/mL).Conclusion: Low serum LPC levels were associated with significantly higher disease severity and 30-day mortality in the elderly patients with CAP. Therefore, serum LPC is a promising predictive biomarker for the early identification of elderly CAP patients with poor prognosis.Keywords: lysophosphatidylcholine, community-acquired pneumonia, biomarker, severity, mortality, propensity score matching

Chunsheng Duan, Yuan Li, Jiansu Ma, Yanglin Song, Lixia Zhou Department of Pediatric Surgery, Xingtai People’s Hospital, Xingtai, Hebei, 054000, People’s Republic of ChinaCorrespondence: Lixia Zhou, Department of Pediatric Surgery, Xingtai People’s Hospital, 16 Hongxing Street, Xingtai, Hebei, 054000, People’s Republic of China, Tel/Fax +86-0319-3286096, Email zhoulx_xt@163.comPurpose: Surgery impairs immune function and increases postoperative complications. B7H3, a co-stimulatory molecule, plays a crucial role in immune regulation. The present study examined the impact of B7H3 on the postoperative immune response in children with acute suppurative appendicitis (ASA) by comparing preoperative and postoperative B7H3 levels in laparoscopic surgery (LA) and open appendectomy (OA).Patients and Methods: 198 pediatric ASA patients were enrolled. The researcher group performed LA, while the control group performed OA. Perioperative time, recovery time of gastrointestinal function, time to pass gas, length of incision, and length of hospitalization were compared in the perioperative period. Additionally, an ELISA assay was conducted to examine the levels of inflammatory factors and B7H3 and CD28. Short-term postoperative complications were also evaluated.Results: Compared with the control group, the research group had a short operative time, gastrointestinal function recovery time, gas time, and hospitalization time. The short-term complication rate was significantly lower in the research group. More importantly, B7H3 and CD28 were insignificantly different preoperatively, but they were all reduced postoperatively. Moreover, the reduction was more pronounced in the research group. The same results were noted in inflammatory factors and immune markers, which were non-significant different preoperatively and were typically reduced postoperatively, particularly in the research group. Finally, postoperative B7H3 was positively correlated with both inflammatory factors and immune cell levels.Conclusion: B7H3 was reduced in both postoperative periods, and the reduction was more pronounced in the LA group. B7H3 may be involved in postoperative recovery by modulating postoperative inflammation and immune responses.Keywords: ASA, laparoscopic surgery, open appendectomy, B7H3, CD298

Xiaojing Liu,&ast; You Song,&ast; Limin Wan, Rong Du Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong Du, Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email dudurong2003@126.comBackground: This study aims to investigate the knowledge, attitudes, and practices (KAP) among patients with systemic lupus erythematosus (SLE) toward disease management and biologic therapy.Methods: This cross-sectional study was conducted between April 20, 2023, and May 5, 2023, among patients with SLE at Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology. A self-designed questionnaire was developed to collect demographic information of SLE patients and assess their KAP.Results: A total of 463 SLE patients participated. The mean scores for knowledge, attitudes, and practices were 8.52 ± 2.36 (possible range: 0– 11), 39.40 ± 3.38 (possible range: 11– 55), and 27.10 ± 6.29 (possible range: 8– 40), respectively. The path analysis demonstrated a significant and positive association between knowledge and attitudes, as indicated by a path coefficient of 0.455 (p < 0.001), and a significant and positive relationship between knowledge and practices, with a path coefficient of 0.709 (p < 0.001).Conclusion: Patients with SLE exhibited insufficient knowledge, negative attitudes, and poor practices.Keywords: knowledge, attitudes, practices, systemic lupus erythematosus, biologic therapy, cross-sectional study

Yanjuan Song,1 Jing Hu,2 Chunlian Ma,3– 5 Hua Liu,3– 5 Zhanghua Li,6 Yi Yang3– 5 1Graduate School, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 2Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, People’s Republic of China; 3Fitness Monitoring and Chronic Disease Intervention Research Center, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 4College of Sports Medicine, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 5Hubei Key Laboratory of Exercise Training and Monitoring, Wuhan Sports University, Wuhan, Hubei Province, People’s Republic of China; 6Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of ChinaCorrespondence: Yi Yang, Fitness Monitoring and Chronic Disease Intervention research center, Wuhan Sports University, Wuhan, Hubei Province, 430079, People’s Republic of China, Tel +86 139 7129 3990, Email yangyi999999@foxmail.com Zhanghua Li, Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei Province, 430074, People’s Republic of China, Tel +86 189 7161 0121, Email lizhanghua_123@163.comAbstract: The development of numerous diseases is significantly influenced by inflammation. Macrophage-derived exosomes (M-Exos) play a role in controlling inflammatory reactions in various conditions, including chronic inflammatory pain, hypertension, and diabetes. However, the specific targets and roles of M-Exos in regulating inflammation in diseases remain largely unknown. This review summarizes current knowledge on M-Exos biogenesis and provides updated information on M-Exos’ biological function in inflammation modulation. Furthermore, this review highlights the functionalization and engineering strategies of M-Exos, while providing an overview of cutting-edge approaches to engineering M-Exos and advancements in their application as therapeutics for inflammation modulation. Finally, multiple engineering strategies and mechanisms are presented in this review along with their perspectives and challenges, and the potential contribution that M-Exos may have in diseases through the modulation of inflammation is discussed.Keywords: inflammation, macrophage-derived exosomes, biological functions, inflammation modulation, engineering strategies

Yirui Song, Qianqian Chen, Lei Wang Department of Psychology, Wuhan Sports University, Wuhan, People’s Republic of ChinaCorrespondence: Lei Wang, Department of Psychology, Wuhan Sports University, No. 461 Luoyu Road, Hongshan District, Wuhan, 430079, People’s Republic of China, Email 378299706@qq.comPurpose: Post-traumatic growth is a significant social issue in the management of active aging in elderly people. This study investigates the influence of familism emotions on post-traumatic growth (PTG) of the elderly, and the mediating role of Taoist personality and sense of community (SOC) therein, to provide a scientific basis for the development of positive aging in the elderly.Methods: A cross-sectional study was conducted in several communities of Hubei Province in China. A total of 338 elderly people were investigated with the Familism Emotion Scale, PTG Scale, Taoist Personality Scale and SOC Scale. SPSS 23.0 was used to derive descriptive statistics and conduct a common method bias test, Pearson correlation analysis, and multiple stepwise regression analysis. Mplus 7.3 was used for structural equation modeling to test the significance of parallel mediation effects on the data.Results: The results show that: (1) Familism emotions, Taoist personality and SOC are positively correlated with PTG; (2) Familism emotions, Taoist personality and SOC can all positively predict PTG in the elderly; (3) Both Taoist personality and SOC partially mediated the link between familism emotions and PTG in the elderly.Conclusion: In the context of particularly constraining societal events such as COVID-19, it is necessary to pay careful attention to the impact of external environmental influences upon the elderly, such as family and community, and to encourage elderly people to cultivate a more Taoist personality. The formation of a Taoist personality offers a promising new focus for research in elderly healthcare.Keywords: familism emotions, post-traumatic growth, Taoist personality, sense of community, elderly

Song Wang,1 Yuanyuan Song,2 Huaguo Zhang,3 Jing Song,4 Xiaoyan Guo,5 Xiaolian Jiang1 1West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Nursing, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4School of Stomatology, Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 5Department of Pharmacy, Dezhou Municipal Hospital, Dezhou, Shandong, People’s Republic of ChinaCorrespondence: Xiaolian Jiang, West China School of Nursing, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Email jangxaolianhl@163.com; jiang_xiaolian@126.comPurpose: This study aimed to improve cancer-related fatigue (CRF) and health outcomes of colorectal cancer patients by understanding the status quo of CRF, exploring the relations of coping, anxiety symptoms, depressive symptoms, body image perception and CRF, and also identifying the factors affecting CRF based on a generalized linear modeling approach.Patients and Methods: An exploratory cross-sectional study was conducted on 370 colorectal cancer patients at two hospitals in Anhui Province, China, from July 2020 to February 2021. The data were collected by using general information questionnaire, cancer fatigue scale, simplified coping style questionnaire, generalized anxiety disorder-7 scale, patient health questionnaire-9, and body image scale. Descriptive statistics, t-tests, one-way analysis of variance, Pearson correlation analyses, and generalized linear model analyses were applied to analyze the data.Results: The average CRF score of the patients was 21.612 (SD=6.160), with a prevalence rate of 69.4% for clinically relevant fatigue. The generalized linear model revealed that: In step 1, gender (female) (B=1.799, Waldχ2=7.506, p=0.006), per capita monthly income (1001– 3000 RMB) (B=− 1.673, Waldχ2=5.536, p=0.019) and treatment modalities (chemotherapy+others) (B=2.425, Waldχ2=8.211, p=0.004) were related to CRF. In step 2, depressive symptoms (B=1.223, Waldχ2=129.019, p< 0.001) and negative coping strategies (B=0.215, Waldχ2=11.347, p=0.001) exhibited significant positive correlations with CRF, positive coping strategies (B=− 0.319, Waldχ2=59.175, p< 0.001) showed significant negative correlations with CRF; While anxiety symptoms (B=0.162, Waldχ2=1.840, p=0.175) and body image perception (B=0.013, Waldχ2=0.048, p=0.826) had no correlations with CRF.Conclusion: The prevalence of CRF was relatively high among colorectal cancer patients. Coping and depressive symptoms were the modifiable influencing factors of CRF. Tailored interventions dedicated to promoting positive coping behavior, diminishing negative coping behavior and reducing depressive symptoms may improve the CRF of patients with colorectal cancer. Healthcare providers working with these patients should receive corresponding education and training in these complementary treatments. Additionally, when developing non-pharmacological interventions, appropriate consideration of the patients’ gender, income condition and the type of anticancer treatment is also necessary.Keywords: colorectal cancer, cancer-related fatigue, coping style, anxiety, depression, body image distress

Yuelin Song,1,2,&ast; Ruizhe Li,1,2,&ast; Lifei Wang,3 Hongjing Wang1,2 1Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongjing Wang, West China Second University Hospital of Sichuan University, No. 20, Section 3, Renmin South Road, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel +86 181 8060 9060, Email whjscdx@163.comAbstract: Primary angiosarcomas are a rare type of soft-tissue sarcomas that originate from endothelial cells. These sarcomas can develop in any part of the body and have a poor prognosis. However, they are commonly found in the skin of elderly white men, particularly on the scalp and head region. Primary angiosarcoma of the cervix is exceptionally rare. To date, only two cases of this disease have been reported worldwide. The diagnosis of the disease is difficult microscopically, requiring immunohistochemistry and genetic testing to distinguish. We report a recent case, in which the lesion was preoperatively considered a high-grade endometrial stromal sarcoma. A 35-year-old woman presented with vaginal bleeding and cervical erosions. A high-grade endometrial stromal sarcoma involving the cervix was considered and a modified radical hysterectomy was performed with bilateral salpingo-oophorectomy and sentinel lymph nodes resection. The gene diagnosis performed by fluorescence in situ hybridization for YWHAE translocation fusion was negative excluding a YWHAE-translocated high-grade endometrial stromal sarcoma. A primary angiosarcoma of the cervix was finally diagnosed. Primary angiosarcoma of the cervix is rare, and gynecologic pathologists do not know it well, so it is easy to be wrongly considered. Immunohistochemistry and genetic testing help confirm the diagnosis.Keywords: angiosarcoma, case report, cervix, genetic testing, immunohistochemistry

Yanyan Song Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Yanyan Song, Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, XingqingDistrict, Yinchuan, 750004, People’s Republic of China, Email nxfysyy@163.com

Merkel cell carcinoma (MCC) incidence has risen to approximately 3,000 cases annually in the USA. Although anti-programmed cell death (ligand) 1 (PD-(L)1) agents are now the first-line treatment for advanced MCC, approximately 50% of such patients do not persistently benefit. In PD-(L)1-refractory cases, ipilimumab (anti-cytotoxic T lymphocyte antigen-4) is often added; however, the extent of the clinical benefit of this combination is controversial. We identified one prospective study, three retrospective studies, and three case reports regarding this combination in refractory MCC. The aggregate response rate from retrospective studies was 32% (13 of 41 patients) with 4 complete responses (CR) and 9 partial responses (PR). In the prospective study, the response rate was very similar at 31% (8 of 26 patients; 4 CR, 4 PR). Response durability was highly variable (range 2 to >43 months), with patients achieving CR having greater durability. Immune-related adverse events (irAEs) were ≥grade III in 29% (retrospective cohort, N=41) and 36% (prospective cohort, N=50). While these aggregate data indicate adding ipilimumab should be considered in this setting, many patients with refractory MCC are ineligible due to comorbidities/irAEs, and approximately 70% will not benefit from this regimen. There is thus a significant unmet need in PD-(L)1-refractory MCC and clinical trials in this setting should be encouraged.

Meijuan Liu,1 Bingyan Cao,1 Qipeng Luo,2 Yanning Song,1 Yuting Shi,1 Ming Cheng,1 Kai Liu,1 Di Mao,1 Xinmeng Wang,1 Chunxiu Gong1 1Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2Department of Pain Medicine, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Chunxiu Gong, Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China, Email chunxiugong@sina.comObjective: To explore the gender-, age-, and weight status-specific prevalence of hyperuricemia (HUA) and its associated risk factors among Chinese children and adolescents with obesity.Methods: A total of 1329 children aged 2– 17 years, who were diagnosed with obesity and hospitalized in our center from January 2016 to December 2022 were recruited. They were divided into mild obesity, moderate obesity, and severe obesity groups. HUA was defined as fasting serum uric acid level > 420 μmol/L for boys and > 360 μmol/L for girls. Multivariate logistic regression analyses were performed to identify risk factors for HUA.Results: The highest proportion of hospitalized obese children was aged 10– 13 years comprising 677 (50.9%) followed by those aged 6– 9 years comprising 348 (26.2%) whereas the least proportion was aged 2– 5 years comprising 76 (5.7%). The above differences in age distribution were still present in subgroup analyses according to weight status. Most hospitalized obese children were boys (64.7%), especially in the severe obesity group (75.0%). The overall estimated prevalence of HUA in obese children was 54.8%. It presented a gradual increase trend over the last 7 years, with more rapidly in boys than in girls. Subgroup analysis by weight status showed that the prevalence of HUA was higher in children with moderate obesity (64.3%) and severe obesity (64.2%) when compared with mild obesity (48.2%) (P all< 0.01). Boys reached a relatively high HUA incidence level (≥ 60%) at age 12, which occurred about 2 years later than in girls (age 10). With 12 years as the cut-off point, a high prevalence of HUA (≥ 60%) was observed in both genders. Multivariable logistic regression analyses showed that boy (OR=2.844, 95% CI 2.024– 3.998), age (OR=1.253, 95% CI 1.155– 1.360), BMI-Z score (OR=2.132, 95% CI 1.438– 3.162), fasting blood glucose (OR=0.907, 95% CI 0.860– 0.956), phosphorus (OR=4.123, 95% CI 2.349– 7.239), alkaline phosphatase (OR=1.002, 95% CI 1.001– 1.004), creatinine (OR=1.067, 95% CI 1.037– 1.098), urea nitrogen (OR=1.193, 95% CI 1.032– 1.378), aspartate aminotransferase (OR=1.016, 95% CI 1.002– 1.030), triglycerides (OR=1.339, 95% CI 1.075– 1.667), and high-density lipoprotein cholesterol (OR=0.381, 95% CI 0.160– 0.910) were independently associated with odds of HUA (P all< 0.05).Conclusion: The prevalence of HUA in Chinese obese children and adolescents is unexpectedly high. Childhood HUA was significantly associated with obesity. Gender and age differences were observed in the association between childhood obesity and HUA. Obese children aged ≥ 12 years should be focused on screening the risk of HUA.Keywords: children, hyperuricemia, body mass index, sex, age, obesity

Yanping Yang,1 Yuanlin Song,1– 3 Dongni Hou2 1Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Lung Inflammation and Injury, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Respiratory Research Institute, Shanghai, People’s Republic of ChinaCorrespondence: Dongni Hou, Shanghai Key Laboratory of Lung Inflammation and Injury, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, People’s Republic of China, Email houdn2014@126.comAbstract: Obesity is a principle causative factor of various metabolic dysfunctions, chronic inflammation, and multi-organ impairment. The global epidemic of obesity has constituted the greatest threat to global health. Emerging evidence has associated obesity with an increased risk of severe infection and poor outcomes from coronavirus disease 2019 (COVID-19). During current COVID-19 pandemic, the interaction between COVID-19 and obesity has exaggerated the disease burden of obesity more than ever before. Thus, there is an urgent need for consideration of universal measures to reduce the risk of complications and severe illness from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in obesity population. In this review, we first summarized the clinical evidence on the effect of obesity on susceptibility, severity, and prognosis of COVID-19. Then we discussed and the underlying mechanisms, including respiratory pathophysiology of obesity, dysregulated inflammation, upregulated angiotensin-converting enzyme 2 (ACE2) expression, hyperglycemia, and adipokines. Finally, we proposed recommendations on how to reduce the spread and pandemic of SARS-CoV-2 infection by prevention and treatment of obesity.Keywords: obesity, COVID-19, metabolic syndrome, severe acute respiratory syndrome coronavirus 2, angiotensin-converting enzyme 2, inflammation

Xing Zhang,1,&ast; Yuanyuan Song,1,&ast; Hongyang Gong,1,&ast; Chunyan Wu,1 Binquan Wang,1 Wenxuan Chen,2 Jiawei Hu,2 Hanhui Xiang,2 Ke Zhang,1 Mingkuan Sun1 1Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2The Second Clinical Medical School, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingkuan Sun, Department of Toxicology, School of Public Health, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, 211166, People’s Republic of China, Email sunmk@njmu.edu.cnAbstract: The increasing use of titanium dioxide nanoparticles (TiO2 NPs) across various fields has led to a growing concern regarding their environmental contamination and inevitable human exposure. Consequently, significant research efforts have been directed toward understanding the effects of TiO2 NPs on both humans and the environment. Notably, TiO2 NPs exposure has been associated with multiple impairments of the nervous system. This review aims to provide an overview of the documented neurotoxic effects of TiO2 NPs in different species and in vitro models. Following exposure, TiO2 NPs can reach the brain, although the specific mechanism and quantity of particles that cross the blood-brain barrier (BBB) remain unclear. Exposure to TiO2 NPs has been shown to induce oxidative stress, promote neuroinflammation, disrupt brain biochemistry, and ultimately impair neuronal function and structure. Subsequent neuronal damage may contribute to various behavioral disorders and play a significant role in the onset and progression of neurodevelopmental or neurodegenerative diseases. Moreover, the neurotoxic potential of TiO2 NPs can be influenced by various factors, including exposure characteristics and the physicochemical properties of the TiO2 NPs. However, a systematic comparison of the neurotoxic effects of TiO2 NPs with different characteristics under various exposure conditions is still lacking. Additionally, our understanding of the underlying neurotoxic mechanisms exerted by TiO2 NPs remains incomplete and fragmented. Given these knowledge gaps, it is imperative to further investigate the neurotoxic hazards and risks associated with exposure to TiO2 NPs. Keywords: TiO2 NPs, neurotoxic effects, oxidative stress, neuronal damage, neurotoxic mechanisms

Rui Zhao, Jing Zhao, Yichuan Song, Wenxuan Fu, Qingtao Wang, Rui Zhang Department of Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Qingtao Wang; Rui Zhang, Department of Clinical Laboratory, Beijing Chao-yang Hospital, Capital Medical University, No. 8, Gongtinan Road, Chao-Yang District, Beijing, 100020, People’s Republic of China, Tel +86 1085231660, Email wqt36@163.com; zr189169@163.comPurpose: Outcomes after autologous stem cell transplantation (ASCT) are quite variable and difficult to predict. Second-generation flow, second-generation sequencing, and other tests are invasive and expensive for patients. In this study, we aimed to analyze laboratory data before and after transplantation to look for laboratory indicators that could predict disease progression in patients with newly diagnosed multiple myeloma (NDMM) patients underwent ASCT.Patients and Methods: Standard complete blood count (CBC) parameters, clinical biochemical, and immunological indicators on day -5 and day 90 after ASCT were obtained. Receiver-operating characteristic (ROC) curve was used to determine the cutoff values, we evaluated the predictive abilities of laboratory parameters for progression-free survival (PFS). Univariate and multivariate analyses were performed to evaluate the prognostic significance of variables associated with the PFS of 166 NDMM who underwent ASCT.Results: At day-5, a low absolute monocyte count (AMC, p=0.001), systemic inflammation response index< 1.56 (SIRI, P=0.03), serum calcium (p=0.02), and albumin (p=0.006) can predict for superior PFS. At Day +90, a high absolute neutrophil count (ANC, p = 0.008) and lymphocyte-to-monocyte ratio (LMR, p = 0.02), a low neutrophil-to-lymphocyte ratio (NLR, p =0.02) and SIRI< 0.41 (p=0.02) predicted for superior PFS.Conclusion: There are inflammation-related indicators derived from peripheral blood cell count (WBCC) – ANC, NLR, SIRI, and LMR - which can serve as potential biomarkers for predicting PFS of NDMM patients underwent ASCT.Keywords: multiple myeloma, autologous stem cell transplantation, SIRI, lymphocyte-to-monocyte ratio

Wanni Cai,1– 3,&ast; Jianbang Kang,4,&ast; Yanbin Ma,1– 3 Donghong Yin,5 Yan Song,5 Yujie Liu,1– 3 Jinju Duan5 1School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 2Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 3Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 4Department of Microbiology, Second Hospital of Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 5Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinju Duan, Department of Pharmacy, Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan, 030001, Shanxi, People’s Republic of China, Tel +86 351 3365713, Email duanjinju@163.comPurpose: In this article, we studied in detail 74 Carbapenem Resistant Klebsiella pneumoniae (CRKP) in Shanxi to provide essential insight into development of effective strategies for control of CRKP.Patients and Methods: From 2018 to 2021, we collected 74 clinical CRKP from 11 hospitals in Shanxi Province. Clinical data were obtained from medical records, and all isolates were subjected to antimicrobial susceptibility testing, multi locus sequence typing, capsular serotypes, resistant gene profiles and virulence gene profiles. The synergistic activity was performed by microdilution checkerboard method.Results: Our study found differences in the clinical characteristics of CRKP between regions in Shanxi. Sequence type (ST) 11 was the dominant ST in Shanxi; however, the ST types in Shanxi had become more diverse over time and the proportion of STs showed a more balanced distribution with a significant decrease in ST11. NDM was the most common carbapenemase in Shanxi. In addition, the STs, carbapenemases, serotypes and virulence gene distribution varied by region in Shanxi. Moreover, tigecycline in combination with carbapenems and aztreonam had an excellent synergistic effect on CRKP in vitro.Conclusion: The results of this study provide essential insight into development of effective strategies for control of CRKP in Shanxi.Keywords: Klebsiella pneumoniae, antimicrobial resistance, carbapenemase, virulence, synergistic effect, China

Lalit Saini,1 James D Griffin,2 Bhavik J Pandya,3 Manasee V Shah,3 Mo Zhou,4 Hongbo Yang,4 Yan Song,4 Deborah A Marshall5 1London Health Sciences Centre, London, Ontario, Canada; 2Dana-Farber Cancer Institute, Boston, MA, USA; 3Astellas Pharma, Inc, Northbrook, IL, USA; 4Analysis Group, Boston, MA, USA; 5Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaCorrespondence: Bhavik J Pandya, Director, Oncology Health Economics and Clinical Outcomes Research, Astellas Pharma, Inc, 1 Astellas Way, Northbrook, IL, 60062, USA, Tel +1 847 226-0066, Email bhavik.pandya@astellas.comPurpose: This study assessed and compared preferences for treatment attributes of maintenance therapies post-hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) and in physicians who treat these patients.Patients and Methods: Patients with AML post HSCT and physicians from the United States, United Kingdom, Canada, and Australia (physicians only) completed a web-based discrete choice experiment (DCE). The DCE used inputs identified via a targeted literature review and qualitative interviews to ascertain relevant treatment attributes and associated levels. Six treatment attributes were selected (chance of 2-year relapse-free survival, quality of life [QoL], risk of serious infections, risk of nausea, chance of achieving transfusion independence, and duration of hospitalization annually), each with three or four levels. The experimental design included 36 choice tasks that presented a pair of hypothetical treatment profiles with varying attribute levels; participants chose a preferred treatment for each choice task. Choice tasks were divided into three blocks of 12 tasks each in the patient survey and 4 blocks of 9 tasks each in the physician survey; survey participants were randomly assigned to one of the blocks. Random parameter logit regression models were used to assess the impact of stated attributes on preferences for maintenance treatment post HSCT.Results: Surveys from 84 patients and 149 physicians were assessed. For patients, QoL was the most important attribute, followed by duration of hospitalization and chance of 2-year relapse-free survival. For physicians, chance of 2-year relapse-free survival was the most important attribute, followed by QoL and risk of serious infections.Conclusion: Differences in how patients and physicians valued post-HSCT maintenance treatment attributes were identified. These differences suggest that patient-centered decision-making may help physicians choose maintenance treatments for patients with AML post HSCT that better meet their treatment needs and improve their treatment satisfaction.Plain Language Summary: Patients with acute myeloid leukemia (AML) are often treated with chemotherapy followed by stem cell transplantation (SCT). Following SCT, evidence suggests that some patients may benefit from maintenance therapy. In this study, researchers surveyed patients and physicians who treat patients with AML to understand what maintenance treatment characteristics they most valued following SCT. Characteristics evaluated during the survey were chance of survival without relapse, impact on quality of life, risk of serious infections, risk of nausea, chance of being free of needing blood transfusions, and impact on annual hospital length of stay. For patients, the most important maintenance treatment characteristics were better quality of life and fewer hospital days annually. For physicians, the most important maintenance treatment characteristic was a higher chance of survival without relapse. These results show differences in maintenance treatment preferences between patients and physicians, suggesting that patient-centered decision-making could be useful when selecting a maintenance treatment for AML after SCT that meets patients’ treatment needs and improves their treatment satisfaction. Keywords: acute myeloid leukemia, hematopoietic stem cell transplantation, maintenance treatment, discrete choice experiment, quality of life, treatment preferences

Yanyan Song Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Yanyan Song, Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004, People’s Republic of China, Email nxfysyy@163.com

Yanqi Song,1 Yeqing Gu,2 Honglei Guo,3 Honghao Yang,4– 6 Xuena Wang,4– 6 Hongmei Wu,4– 6 Aidi Wang,1 Haijin Wang,1 Quan Zhang,1 Qing Zhang,7 Li Liu,7 Ge Meng,6 Baoshan Liu,1 Kaijun Niu4– 6 1Department of Traditional Chinese Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People’s Republic of China; 3School of Graduate, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4School of Public Health, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 5School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 6Nutritional Epidemiology Institute, Tianjin Medical University, Tianjin, People’s Republic of China; 7Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Kaijun Niu, Nutritional Epidemiology Institute, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, People’s Republic of China, Tel +86-22-83336613, Email nkj0809@gmail.com; niukaijun@tmu.edu.cn Baoshan Liu, Department of Traditional Chinese Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Tel +86-22-60362808, Email lbs-cd@163.comPurpose: The prevalence of benign prostatic hyperplasia (BPH) in the general Chinese adult male population has risen sharply over the past few decades. Increasing evidence suggests that inflammation plays an important role in the pathogenesis of BPH. To better understand the role of inflammation in the pathogenesis of BPH, we can use the neutrophil-to-lymphocyte ratio (NLR) because it is a simple and effective marker of inflammation and immunity. This study aims to prospectively investigate the association between NLR levels and the prevalence of BPH in a general Chinese adult male population.Patients and Methods: This study included a total of 15,783 male participants free from BPH at baseline. NLR was measured according to the complete blood count. BPH was defined as total prostate volume (TPV) ≥ 30 mL, and TPV was determined by transabdominal ultrasonography. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for BPH risk with NLR levels.Results: During a median follow-up of 2.7 years, 5078 BPH cases were documented. After adjusting for age, body mass index, smoking, alcohol, education, occupation, income, physical activity, total energy intake, personal and family history of disease, and inflammation markers, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.08 (95% CIs 0.99, 1.17), 1.10 (95% CIs1.02, 1.19), and 1.12 (95% CIs1.03, 1.21), respectively, for participants with NLR in the first, second, third, and fourth quartiles (P for trend < 0.01).Conclusion: Higher NLR levels were associated with a higher risk of BPH in Chinese adult male population. Our findings support the notion that NLR levels may be an important target for BPH prevention and intervention.Keywords: neutrophil to lymphocyte ratio, inflammation, benign prostatic hyperplasia, prospective cohort study

Shuo Tian,1,2 Lin Guo,3 Yagang Song,1,2 Huiyan Yang,1 Jia Wang,3 Jingyi Qiao,1,2 Xiangxiang Wu,1,2 Ming Bai,1,2 Mingsan Miao1,2 1Academy of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 2Henan Collaborative Innovation Center for Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 3Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of ChinaCorrespondence: Mingsan Miao, Henan Collaborative Innovation Center for Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China, Tel/Fax +86 371 65962546, Email miaomingsan@hactcm.edu.cnPurpose: Radix Salvia miltiorrhiza (RSM), a commonly used medicinal plant, has been reported to have anti-inflammatory effects, but relevant studies on burn injuries are lacking. We investigated the anti-inflammation and wound healing (WH) effects of an aqueous extract of RSM on a burn model in rats.Methods: The effects of RSM were studied by heat-induced burns in rats, treatment with vehicle, Jinwanhong ointment, and RSM (1.5 or 0.75 g/mL). Indicators of burn tissue (BT) were photographed by digital machines and analyzed. The microcirculation in BT was detected by scattered full-frame real-time imaging. Levels of inflammatory mediators and growth factors were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. Local pathologic changes in BT were observed by hematoxylin-and-eosin (HE) staining. Ultrahigh pressure liquid chromatography–linear ion trap–Orbitrap mass spectrometry (UHPLC–LTQ–Orbitrap-MS) was used to explore the absorption of RSM in local skin, subcutaneous tissue, muscle tissue, serum, liver tissue, and kidney tissue.Results: RSM treatment could reduce the wound area, increase percent WH, increase blood perfusion in BT, reduce serum levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α (TNF-α), increase levels of epidermal growth factor (EGF), transforming growth factor (TGF)-β, and hydroxyproline (Hyp) in serum, and increase protein expression of basic fibroblast growth factor (bFGF), TGF-β 1, EGF, and insulin-like growth factor-1 (IGF)-1 in skin tissues. RSM treatment led to micro-absorption in the skin, subcutaneous tissues, and muscle, but not in the blood, liver, or kidney.Conclusion: RSM may promote WH by exerting anti-inflammatory effects, improving local-wound microcirculation, and accelerating the metabolism at the wound surface.Keywords: Radix Salvia miltiorrhiza, burns, anti-inflammatory, wound healing

Tingyu Liang,&ast; Yixuan Song,&ast; Lingui Gu, Yu Wang, Wenbin Ma Department of Neurosurgery, 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: Wenbin Ma; Yu Wang, Email mawb2001@hotmail.com; ywang@pumch.cnAbstract: Glioblastoma (GBM) is the most common malignant primary brain cancer in adults. It is always resistant to existing treatments, including surgical resection, postoperative radiotherapy, and chemotherapy, which leads to a dismal prognosis and a high relapse rate. Therefore, novel curative therapies are urgently needed for GBM. Chimeric antigen receptor T (CAR-T) cell therapy has significantly improved life expectancy for hematological malignancies patients, and thus it increases the interest in applying CAR-T cell therapy for solid tumors. In the recently published research, it is indicated that there are numerous obstacles to achieve clinical benefits for solid tumors, especially for GBM, because of GBM anatomical characteristics (the blood–brain barrier and suppressive tumor microenvironment) and the tumor heterogeneity. CAR-T cells are difficult to penetrate blood–brain barrier, and immunosuppressive tumor microenvironment (TME), which induces CAR-T cell exhaustion, impairs CAR-T cell therapy response. Moreover, under the pressure of CAR-T cell therapy, the tumor heterogeneity and tumor plasticity drive tumor evolution and therapy resistance, such as antigen escape. Nonetheless, scientists strive for strategies to overcome these hurdles, including novel CAR-T cell designs and regional delivery. For instance, the structure of multi-antigen-targeted CAR-T cells can enrich CAR-T accumulation in tumor TME and eliminate abundant tumor cells to avoid tumor antigen heterogeneity. Additionally, paired with an immune modifier and one or more stimulating domains, different generation of innovations in the structure and manufacturing of CAR-T cells have improved efficacy and persistence. While single CAR-T cell therapy receives limited clinical survival benefit. Compared with single CAR-T cell therapy, the combination therapies have supplemented the treatment paradigm. Combinatorial treatment methods consolidate the CAR-T cells efficacy by regulating the tumor microenvironment, optimizing the CAR structure, targeting the CAR-T cells to the tumor cells, reversing the tumor-immune escape mechanisms, and represent a promising avenue against GBM, based on multiple impressive research. Moreover, exciting results are also reported to be realized through combining effective therapies with CAR-T cells in preclinical and clinical trials samples, have aroused inspiration to explore the antitumor function of combination therapies. In summary, this study aims to summarize the limitation of CAR-T cell therapies and introduces novel strategies to enhance CAR-T cell function as well as prospect the potential of the therapeutic combination.Keywords: CAR-T, GBM, novel strategies, therapeutic combination

Yanmei Song,&ast; Huiyuan Chu,&ast; Fang Liu, Wenjie Guo, Na Gao, Che Chen, Shisan Bao Department of Clinical Laboratory Diagnostics, School of Public Health Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Che Chen; Shisan Bao, Department of Clinical Laboratory Diagnostics, School of Public Health Gansu University of Chinese Medicine, 35, Dingxi East Road, Chengguan, Lanzhou, Gansu, 730000, People’s Republic of China, Tel +86 187 09312856 ; +81 180 176 84959, Email chen72123@163.com; profbao@hotmail.comPurpose: To investigate the role of IL-36 in the tumorigenesis of hepatocellular carcinoma (HCC). IL-36 composed of a natural antagonist (IL-36Ra) and three agonists (IL-36α, -β, -γ) that stimulate inflammation by binding to a common receptor consisting of IL-36R and IL-1RAcP. HCC is a common malignancy associated with high morbidity and mortality, often diagnosed at later stages. Although the exact role of IL-36α in HCC remains controversial, it is hypothesized that it may play a significant role in the development and progression of this cancer.Materials and Methods: In the current study, we measured both circulating and intrahepatic levels of IL-36α from HCC patients and healthy controls, using ELISA. The association between IL-36 and the differentiation of HCC was determined. Furthermore, the role IL-36 in both HCC and non-HCC cell lines was evaluated in vitro.Results: Circulating and intra-hepatic IL-36α was inversely correlated with differentiation of HCC, suggesting that IL-36α contribute to protection during the development of HCC. Based on bioinformatics, miR-27b-3p is closely related to downstream IL-36α. Thus, we determined miR-27b-3p expression in HCC tissues, showing upregulated miR-27b-3p was inversely correlated with IL-36α in HCC, perhaps via CXCL1 in HCC cells. It was confirmed that IL-36α inhibited HCC proliferation, viability and migration in vitro, consistent with reduced the expression of cytokines IL-1β, IL-18, implying that IL-36α inhibited the possible involvement of pyroptosis.Conclusion: Our data suggests that IL-36α may be a potential therapeutic target and a prediction biomarker for the management of HCC.Keywords: hepatocellular carcinoma, interleukin-36α, prognosis, biomarker

Yi Jiang,1 Yanyan Song2 1Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710000, People’s Republic of China; 2Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Yanyan Song, Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004, People’s Republic of China, Tel +86 951-6743014, Fax +86 951-6744302, Email nxfysyy@163.comObjective: To investigate the risk factors and intervention strategies for the development of acute kidney injury (AKI) after cardiac valve replacement with extracorporeal circulation.Methods: Retrospective analysis of the clinical data of a total of 106 patients diagnosed with heart valve disease and undergoing extracorporeal circulation heart valve replacement surgery from January 2021 to December 2021 in the Department of Cardiac and Major Vascular Surgery of our hospital. The two groups were divided into AKI and non-AKI groups according to whether acute kidney injury occurred after surgery, and the preoperative, intraoperative and postoperative clinical data were compared. Single-factor analysis and multi-factor logistic regression analysis were used to explore the risk factors for acute kidney injury after extracorporeal heart valve replacement, and to improve the prognosis by giving kidney function protection strategies as early as possible.Results: Univariate analysis showed that age, preoperative blood creatinine > 130umol/L, LVEF < 45%, presence of subacute infective endocarditis (SIE), concurrent coronary artery bypass grafting (CABG), time to extracorporeal circulation, time to surgery, MAP < 70mmHg, urine output < 0.5mL/(kg-h), pulmonary infection, low cardiac output, and bacteraemia were risk factors for postoperative AKI. Multi-factor regression analysis showed that preoperative blood creatinine > 130umol/l, LVEF < 45%, combined infective endocarditis, extracorporeal circulation time > 2h, intraoperative and postoperative hypotension, low cardiac output, and postoperative bacteremia were independent risk factors for postoperative AKI.Conclusion: Active intervention strategies in the perioperative period can reduce the occurrence of postoperative AKI and improve patient prognosis.Keywords: heart valve replacement surgery, acute kidney injury, risk factors, intervention strategies

Shanshan Li,1,&ast; Cheng Yang,1,&ast; Junqiang Li,1,&ast; Chao Zhang,1 Liaoliao Zhu,1 Yang Song,1 Yongdong Guo,1 Ronglin Wang,1 Dongxue Gan,1 Jingjie Shi,1 Peixiang Ma,1 Fei Gao,2 Haichuan Su1 1Department of Oncology, The Second Affiliated Hospital, Air Force Medical University, Xi’an City, People’s Republic of China; 2Center for Peptide Functional Materials and Innovative Drugs, Institute of Translational Medicine, Shanghai University, ShangHai City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haichuan Su, Department of Oncology, The Second Affiliated Hospital, Air Force Medical University, No. 569 Xinsi Road, Baqiao District, Xi’an City, People’s Republic of China, Email suhc@fmmu.edu.cn Fei Gao, Center for Peptide Functional Materials and Innovative Drugs, Institute of Translational Medicine, Shanghai University, No. 99 ShangDa Road, BaoShan District, ShangHai City, People’s Republic of China, Email flyhightly@shu.edu.cnAbstract: Pluronic F127 hydrogel biomaterial has garnered considerable attention in wound healing and repair due to its remarkable properties including temperature sensitivity, injectability, biodegradability, and maintain a moist wound environment. This comprehensive review provides an in-depth exploration of the recent advancements in Pluronic F127-derived hydrogels, such as F127-CHO, F127-NH2, and F127-DA, focusing on their applications in the treatment of various types of wounds, ranging from burns and acute wounds to infected wounds, diabetic wounds, cutaneous tumor wounds, and uterine scars. Furthermore, the review meticulously examines the intricate interaction mechanisms employed by these hydrogels within the wound microenvironment. By elucidating the underlying mechanisms, discussing the strengths and weaknesses of Pluronic F127, analyzing the current state of wound healing development, and expanding on the trend of targeting mitochondria and cells with F127 as a nanomaterial. The review enhances our understanding of the therapeutic effects of these hydrogels aims to foster the development of effective and safe wound-healing modalities. The valuable insights provided this review have the potential to inspire novel ideas for clinical treatment and facilitate the advancement of innovative wound management approaches.Keywords: Pluronic F127, F127-CHO, F127-NH2, F127-DA, wound healing and repair

Yanqi Song,1 Yeqing Gu,2 Honglei Guo,3 Honghao Yang,4– 6 Xuena Wang,4– 6 Hongmei Wu,4– 6 Aidi Wang,1 Mengxiao Wang,7 Haijin Wang,1 Qing Zhang,8 Li Liu,8 Ge Meng,6,8– 10 Baoshan Liu,1 Kaijun Niu4– 6 1Department of Traditional Chinese Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People’s Republic of China; 3Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4School of Public Health of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 5School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 6Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 7Binzhou Hospital of Chinese Medicine, Shandong, People’s Republic of China; 8Health Management Centre, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 9Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, People’s Republic of China; 10Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Kaijun Niu; Baoshan Liu, Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, People’s Republic of China, Tel +86-22-83336613, Email nkj0809@gmail.com; niukaijun@tmu.edu.cn; lbs-cd@163.comPurpose: This study aimed to prospectively investigate the association between mean platelet volume (MPV) levels and risk of benign prostatic hyperplasia (BPH) in a general Chinese adult male population, and assessed this association in metabolic syndrome (MetS) patients.Patients and methods: This study included a total of 14,923 male participants free from BPH at baseline. MPV was measured by the method of laser-based flow cytometric impedance according to the complete blood sample. BPH was defined as total prostate volume (TPV) ≥ 30 mL, TPV was determined by transabdominal ultrasonography. Multivariable Cox proportional hazards models were fitted to calculate hazards ratios (HRs) and corresponding 95% confidence intervals (CIs) for BPH risk with NLR levels.Results: During a median follow-up of 2.7 years, 4848 BPH cases were documented in total male participants, and 1787 BPH cases were documented in MetS participants. After adjusting for age, body mass index, smoking, alcohol and personal and family history of disease, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.03 (95% CIs 0.96, 1.11), 1.00 (95% CIs 0.92, 1.08) and 0.98 (95% CIs 0.90, 1.06), respectively, for participants with MPV in the 1st, 2nd, 3rd and 4th quartiles (P for trend = 0.47). In MetS patients, the multivariable-adjusted HRs of BPH were 1.00 (reference), 1.03 (95% CIs 0.90, 1.16), 0.99 (95% CIs 0.87, 1.14) and 1.01 (95% CIs 0.89, 1.15) (P for trend= 0.98), respectively.Conclusion: A non-significant association was observed between MPV levels and risk of BPH, and no association in this association in MetS patients. Our findings support the notion that MPV levels may not be a target for BPH prevention and intervention.Keywords: mean platelet volume, inflammation, benign prostatic hyerplasia, metabolic syndrome, prospective cohort study

Yan Song,1 Jian-Yu E,1 Tracy Guo,1 Rahul Sasane,2 Steve Arcona,2 Nirmal Keshava,2 Eric Wu1 1Analysis Group, Inc, Boston, MA, USA; 2Cerevel Therapeutics, Cambridge, MA, USACorrespondence: Yan Song, Analysis Group, Inc, 111 Huntington Ave, 14th Floor, Boston, MA, 02199, USA, Tel +1 617-425-8272, Email yan.song@analysisgroup.comBackground: Studies on real-world treatment patterns and long-term economic burden of Parkinson’s disease (PD) have been limited.Objective: To assess treatment patterns, healthcare resource utilization (HRU), and costs associated with PD symptoms and treatment-related adverse events (AEs) among Medicare beneficiaries in the United States.Methods: A 100% Medicare Fee-For-Service data (2006– 2020) of patients with PD were analyzed. PD treatment patterns were described for the subset of patients who had no previously observed PD treatments or diagnoses (ie, the incident cohort). HRU and healthcare costs associated with PD symptoms were assessed for all patients with PD (ie, the overall cohort) and that associated with treatment-related AEs were assessed for the subset of patients who received PD treatments after PD diagnosis (ie, the active treatment cohort), using longitudinal models with repeated measures.Results: Overall, 318,582 patients were included (mean age at PD diagnosis: 77.4 years; 53.3% female). Among patients in the incident cohort (N=214,829), 51.1% initiated levodopa monotherapy and 5.9% initiated dopamine agonists (DAs) monotherapy as first-line treatment. The proportion of incident patients treated with DAs and other PD therapies generally increased from post-diagnosis years 1 to 10. The median time from diagnosis to PD treatment initiation was 2.0 months; the median time to treatment discontinuation was the longest with levodopa (18.7 months), followed by DAs (9.5 months). In the overall cohort, PD symptoms, especially motor symptoms and severe motor symptoms, were associated with significantly higher rates of HRU and costs. In the active treatment cohort (N=234,298), treatment-related AEs were associated with significantly higher rates of HRU and medical costs.Conclusion: While levodopa is still the mainstay of PD management, considerable heterogeneity exists in real-world treatment patterns. Overall, PD symptoms and AEs were associated with significantly higher HRU and healthcare costs, suggesting unmet medical needs for PD treatments with better tolerability profiles.Keywords: Parkinson’s disease, treatment patterns, adverse events, healthcare resource utilization, healthcare costs

Yanyan Song, Jian Yang Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Yanyan Song, Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004, People’s Republic of China, Email nxfysyy@163.com

Yanyan Song, Jiwei Gu Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Yanyan Song, Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750004, People’s Republic of China, Email nxfysyy@163.com

Dave Singh,1 Gerard J Criner,2 Alvar Agustí,3 Mona Bafadhel,4 Johan Söderström,5 Gabriela Luporini Saraiva,6 Yue Song,6 Idlir Licaj,7 Maria Jison,6 Ubaldo J Martin,6 Ioannis Psallidas8 1Manchester University NHS Foundation Hospital Trust, the University of Manchester, Manchester, UK; 2Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; 3Respiratory Institute (Hospital Clinic), IDIBAPS, CIBERES, Catedra Salud Respiratoria (University of Barcelona), Barcelona, Spain; 4School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; 5Late-stage Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; 6Late-stage Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 7Cytel Inc, Cambridge, MA, USA; 8Late-Stage Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UKCorrespondence: Dave Singh, Medicines Evaluation Unit, Langley Building, University Hospital of South Manchester, NHS Foundation Trust, Southmoor Road, Manchester, M23 9QZ, UK, Tel +44 (0)161 946 4073, Email dsingh@meu.org.ukAbstract: Exacerbations in chronic obstructive pulmonary disease (COPD), which tend to occur in clusters and increase with disease severity, come with high societal and economic burdens. Prevention and delay of recurrent exacerbations is an unmet and significant therapeutic need for patients with COPD. GALATHEA (NCT02138916) and TERRANOVA (NCT02155660) were trials assessing efficacy of benralizumab in patients with frequent COPD exacerbations despite treatment. Although these studies found that benralizumab given as an add-on treatment did not significantly reduce annual rates of COPD exacerbations after 56 weeks of treatment, in the following exploratory post hoc analysis of the GALATHEA and TERRANOVA trials we identified a potential responder population in which treatment with benralizumab prevents recurrent COPD exacerbations during 30- and 90-day periods following an initial exacerbation, a vulnerable period for an exacerbation to occur. This responder population was characterized by high blood eosinophil counts and frequent previous exacerbations despite optimized triple therapy. These results highlight the importance of targeted therapies for high-risk populations and merit further research into the benefits of biologic therapies for COPD exacerbations.Keywords: COPD, recurrent exacerbations, benralizumab, eosinophil

Xianqin Song,1 Yu Song,1 Quanping Ma,2 Kehua Fang,3 Xiaotian Chang1 1Medical Research Center of the Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Clinical Laboratory, The fourth People’s Hospital of Jinan, Jinan, Shandong, People’s Republic of China; 3Clinical Laboratory of the Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Xiaotian Chang, Medical Research Center of the Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China, Tel/Fax +86 0532-82917331, Email changxt@126.comPurpose: Vascular calcification is a hallmark of atherosclerosis (AS). We and others confirmed that carbonic anhydrase I (CA1) and CA2 increased expression and catalyzed calcium deposition in atherosclerotic aortas. Macrophages have been demonstrated to be strongly related to AS. This study aimed to clarify how and which macrophage subtypes regulate CA1 and CA2 expression to stimulate aortic calcification.Methods and Results: THP-1 cells were induced to form M0, M1 and M2 macrophage subtypes. These cells and their culture supernatants were separately incubated with human vascular smooth muscle cells (VSMCs). Calcification was strongly increased in VSMCs treated with β-GP, a chemical inducer of cellular calcification, following incubation with M1 macrophages or their culture supernatants, and was much higher than that in VSMCs treated with β-GP alone. Meanwhile, the expression of CA1 and CA2, as well as calcification marker genes, including Runx2, BMP-2 and ALP, was increased in VSMCs during this process. TNF-α levels were also increased in the culture medium of M1 macrophages. M0 and M2 macrophages or their supernatants did not significantly stimulate calcification in VSMCs. Following transfection with anti-CA1 or CA2 siRNAs, β-GP-induced VSMCs showed decreased calcification, but the calcification level was partially increased when those VSMCs were incubated with the supernatants of M1 macrophages, while CA1 and CA2 expression as well as TNF-α levels were also elevated. When VSMCs were treated with TNF-α without β-GP induction, calcification and the expression of CA1 and CA2 were also significantly increased.Conclusion: The results of this study suggest that M1 macrophages can increase CA1 and CA2 expression to promote atherosclerotic calcification in VSMCs by secreting TNF-α.Keywords: atherosclerosis, calcification, carbonic anhydrase I, carbonic anhydrase II, macrophages, TNF-&#x03B1