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

Liuping Cui,1,2 Ran Liu,1 Fubo Zhou,1 Yumei Liu,1 Bing Tian,1 Ying Chen,2,&ast; Yingqi Xing1,3,4,&ast; 1Department of Vascular Ultrasound, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurology, The First Hospital of Jilin University, Changchun, People’s Republic of China; 3Beijing Diagnostic Center of Vascular Ultrasound, Beijing, People’s Republic of China; 4Center of Vascular Ultrasound, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingqi Xing, Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, 45 Changchun Road, Beijing, Xicheng District, 100053, People’s Republic of China, Tel +86-18610047846, Email xingyq2009@sina.comPurpose: Intraplaque neovascularization, assessed using contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke. It remains unclear whether detection of intraplaque neovascularization combined with color Doppler ultrasound (CDUS) provides additional value compared with CDUS alone in assessing ischemic stroke risk. Therefore, we investigated the clinical value of combined CEUS, CDUS, and clinical features for ischemic stroke risk stratification.Patients and Methods: We recruited 360 patients with ≥ 50% carotid stenosis between January 2019 and September 2022. Patients were examined using CDUS and CEUS. Covariates associated with ischemic stroke were identified using multivariate logistic regression analysis. The discrimination and calibration were verified using the C-statistic and Hosmer–Lemeshow test. The incremental value of intraplaque neovascularization in the assessment of ischemic stroke was analyzed using the Delong test.Results: We analyzed the data of 162 symptomatic and 159 asymptomatic patients who satisfied the inclusion and exclusion criteria, respectively. Based on multivariate logistic regression analysis, we constructed a nomogram using intraplaque neovascularization, degree of carotid stenosis, plaque hypoechoicity, and smoking status, with a C-statistic of 0.719 (95% confidence interval [CI]: 0.666– 0.768) and a Hosmer–Lemeshow test p value of 0.261. The net reclassification index of the nomogram was 0.249 (95% CI: 0.138– 0.359), and the integrated discrimination improvement was 0.053 (95% CI: 0.029– 0.079). Adding intraplaque neovascularization to the combination of CDUS and clinical features (0.672; 95% CI: 0.617– 0.723) increased the C-statistics (p=0.028).Conclusion: Further assessment of intraplaque neovascularization after CDUS may help more accurately identify patients at risk of ischemic stroke. Combining multiparametric carotid ultrasound and clinical features may help improve the risk stratification of patients with ischemic stroke with ≥ 50% carotid stenosis.Plain Language Summary: We studied whether using contrast-enhanced ultrasound (CEUS) to detect intraplaque neovascularization could help better determine the risk of ischemic stroke. We compared the combined use of color Doppler ultrasound (CDUS) and CEUS with CDUS alone in patients with more than 50% carotid narrowing. Our findings showed that combining clinical details, CDUS, and CEUS was more effective (0.719 vs 0.672). This means that CEUS provides extra insight when gauging ischemic stroke risk compared with CDUS alone. This could help in accurately identifying patients at high risk of stroke. However, more extensive studies are needed to fully understand the role of these tests in the evaluation of stroke risk. Keywords: atherosclerosis, contrast-enhanced ultrasound, vulnerable plaque, carotid ultrasound

Chaoe Zhou,1,&ast; Jun Li,2,&ast; Fude Zhou,3 Lei Huang,4 Xinmin Liu,1 Haichao Li5 1Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 3Renal Division, Department of Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Clinical Laboratory, Peking University First Hospital, Beijing, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinmin Liu, Department of Geriatrics, Peking University First Hospital, Tel +86-10-8357-2128, Beijing, 100034, People’s Republic of China, Email lxm2128@163.com Haichao Li, Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Tel +86-10-8357-2128, Beijing, 100034, People’s Republic of China, Email lhch91767@sina.comAbstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an acute, rare and potentially fatal drug reaction. To date, limited studies have reported secondary Pneumocystis jirovecii pneumonia (PJP) infection during the treatment of DRESS syndrome. A 53-year-old man was admitted to the hospital due to a persistent fever lasting for 5 days. He had a medical history of hypertension, psoriasis, urticaria, and had recently been treated with carbamazepine for nerve spasm two weeks ago. After admission, the patient presented with a high fever accompanied by chills, abdominal pain, bilateral upper limb muscle pain, and generalized lymph nodes enlargement. Laboratory tests revealed elevated eosinophils and atypical lymphocytes. Subsequently, the patient developed multiple internal organ complications, including oliguria, elevated serum creatinine, liver enzymes, and cardiac troponin I. Based on diagnostic criteria, the patient was diagnosed with DRESS syndrome. To manage the DRESS syndrome, the patient was successively or simultaneously prescribed methylprednisolone, cyclosporin and intravenous immunoglobulin, resulting in an improvement of the condition. However, during the treatment, the patient was infected with Pneumocystis jirovecii. Despite targeted therapy with trimethoprim/sulfamethoxazole, primaquine and clindamycin successively, no remission was observed. Chest CT scans exhibited multiple exudations in both lungs, indicative of interstitial pneumonia. Unfortunately, the patient’s oxygenation progressively declined, leading to his untimely demise. This rare case further highlights the need for clinicians to be aware of the risk of Pneumocystis jirovecii infection in DRESS syndrome patients treated with long-term and high-dose glucocorticoid therapy.Keywords: DRESS syndrome, Pneumocystis jirovecii pneumonia, carbamazepine, glucocorticoid therapy, case report

Hongxia Wang,1,&ast; Fating Zhou,2,&ast; Zhilin Li,1 Yulan Ding,1 Qian Wen,1 Quanxing Tang1 1Department of General Practice, People’s Hospital of Deyang City, Deyang, Sichuan, People’s Republic of China; 2Emergency Department, Chongqing Emergency Medical Center, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongxia Wang, Department of General Practice, People’s Hospital of Deyang City, Deyang, Sichuan, People’s Republic of China, Email HongXia.W@hotmail.comBackground: Streptococcus constellatus rarely causes pyopneumothorax, which is a serious state and requires a surgery. However, not every patient can tolerate surgery and individualized solutions are needed. Furthermore, many known situations are risk factors of S. constellatus infection, but S. constellatus pyopneumothorax associated with Hashimoto’s thyroiditis has not been reported.Case Presentation: We present the case of a 74-year-old male with multiple encapsulated pyopneumothorax caused by S. constellatus. Given his respiratory failure, we provided two-stage percutaneous right empyema radiography for catheter drainage in the radiology interventional department instead of surgery. Moreover, an occult Hashimoto’s thyroiditis was discovered in the patient, which was possibly associated with S. constellatus pyopneumothorax. Levothyroxine was administered to improve his situation.Conclusion: To our knowledge, it is the first case described in this context. We provided an alternative treatment for S. constellatus encapsulated pyopneumothorax in patient who might not tolerate surgery. We also revealed the possible relationship between S. constellatus pyopneumothorax and Hashimoto’s thyroiditis.Keywords: radiology interventional, Streptococcus constellatus, pyopneumothorax, Hashimoto’s thyroiditis

Ju Kuang, Zhihai Luo, Fu Zhou Department of Respiratory and Critical Care Medicine, Affiliated Banan Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Fu Zhou, Tel +86-17702395630, Email 1163629567@qq.comAbstract: A 66-year-old male patient diagnosed with small-cell lung cancer received chemotherapy and immunotherapy, resulting in successful tumor control. However, the patient subsequently experienced a fever and rapid progression of the pulmonary cavity. Despite sampling bronchoscopic bronchoalveolar lavage fluid for targeted next-generation sequencing (tNGS), the cause remained unidentified. Adding bronchoalveolar lavage fluid to sense metagenomic next-generation sequencing (mNGS) confirmed the infection caused by actinomycetes. The patient’s condition improved after active anti-infection treatment. This case was further analyzed and discussed through a comprehensive literature review, focusing on molecular microbiological diagnosis and treatment processes. The points outlined were as follows: the advancement of molecular microbiology has gradually reduced the challenges associated with diagnosing rare infectious diseases such as pulmonary actinomycosis. Additionally, in immunodeficient individuals, certain infectious diseases with a chronic course may exhibit acute and aggressive characteristics, which is of concern to all colleagues. Currently, tNGS and mNGS are widely employed in clinical settings as practical tools for diagnosing infectious diseases. Notably, these two methods are not substitutes for each other but complement each other.Keywords: pulmonary actinomycosis, lung cancer, targeted next-generation sequencing, metagenomic next-generation sequencing

Ziyun Wang,1,2,&ast; Yao Wang,1,2,&ast; Yuqi Ji,1,2 Ziwei Yang,1,2 Yixiu Pei,3 Jiankun Dai,4 Yong Zhang,5 Fuqing Zhou1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, People’s Republic of China; 2Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang, 330006, People’s Republic of China; 3Department of Radiology, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi, 341000, People’s Republic of China; 4MR Advanced Application, GE Healthcare, Beijing, 100176, People’s Republic of China; 5Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Zhang, Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 791 8869 5036, Email zy830226@163.com Fuqing Zhou, Department of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng, Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 791 8869 5132, Email ndyfy02301@ncu.edu.cnPurpose: To explore resting-state functional connectivity (rsFC) of the amygdala in patients with low-back-related leg pain (LBLP).Patients and Methods: For this prospective study, a total of 35 LBLP patients and 30 healthy controls (HCs) were included and underwent functional MRI and clinical assessments. Then, patients with LBLP were divided into acute LBLP (aLBLP) and chronic LBLP (cLBLP) subgroups. We further evaluated the between-group rsFC differences using left and right amygdala seeds in a whole-brain voxel analysis strategy. Finally, we performed correlation analysis between the rsFC values of altered regions and clinical indices.Results: Compared to HCs, hypoconnectivity of the amygdala was observed in LBLP patients (P < 0.01, with correction). The amygdala’s rsFC pattern was different between aLBLP and cLBLP patients: decreased the amygdala’s FC to the right putamen, to the right paracentral lobule (PCL), or to the right posterior temporal lobe in aLBLP patients, while right amygdala to the bilateral anterior cingulate cortex (ACC) and the left postcentral gyrus (PoCG) in cLBLP patients. Correlation analysis showed that lower rsFC of the left amygdala to the right PCL was correlated with the von Frey filament (vF) test values of the left lumbar (p = 0.025) and right lumbar (p = 0.019) regions, and rsFC of the right amygdala to the left PoCG was correlated with lower vF test values of the left lumbar (p = 0.017), right lumbar spine (p = 0.003); to right PoCG was correlated with calf (p = 0.015); the rsFC of the right amygdala to bilateral ACC was negatively correlated with the pain rating index (p = 0.003).Conclusion: LBLP patients showed amygdala hypoconnectivity, and the altered pattern of amygdala rsFC was different in the acute and chronic phases. Moreover, the amygdala hypoconnectivity was related to individual mechanical sensitivity (vF test) in LBLP patients.Keywords: amygdala, resting-state functional MRI, low-back-related leg pain, acute pain, chronic pain

Qiuying Qin,1,2,&ast; Xiaoxuan Kou,1,2,&ast; Yuanyuan Zheng,1,2 Fei Zhou,1,2 Xiaoyong Zhang,1,2 Hongyan Liu1,2 1State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyong Zhang; Hongyan Liu, Email xiaoyzhang@smu.edu.cn; liuhongyan205628@163.comPurpose: In recent years, a new therapeutic approach, known as immune checkpoint blockade (ICB), has been proposed as approach to improve outcomes in patients with intermediate stage (Barcelona Clinic Liver Cancer, BCLC B) or advanced stage (BCLC C) hepatocellular carcinoma (HCC). Unfortunately, only a select patients can benefit from ICB. Hence, biomarkers that can predict the success and survival of treatment are still necessary.Patients and Methods: Between 2018 to 2021, 132 patients received ICB treatment for intermediate or advanced stage HCC. Based on the early kinetics of C-reactive protein (CRP), the patients were classified into three groups. The study endpoints were progression-free survival (PFS) and overall survival (OS).Results: Our findings support the predictive power of early CRP kinetics in determining immunotherapy response for intermediate or advanced HCC. Objective response rates (ORR) were found in 41.2% of CRP flare-responders, 13.3% of CRP responders, and 3.5% of CRP non-responders (p< 0.001). Disease control rates (DCR) in the three groups were substantially different (p< 0.001). The improved PFS and OS were strongly correlated with the early kinetics of CRP. Compared to CRP non-responders, CRP responders, especially CRP flare-responders, had significantly longer PFS (median PFS: CRP flare-responders: 11.6 months vs CRP responders: 5.2 months vs CRP non-responders: 2.3 months, p< 0.001).Conclusion: The CRP flare response robustly predicts the immunotherapy response and outcomes in patients with HCC. Early CRP kinetics may be an inexpensive, easily implemented and non-invasive biomarker to anticipate response to ICB therapy in intermediate or advanced HCC, with the potential to optimize treatment monitoring.Keywords: hepatocellular carcinoma, C‐reactive protein kinetics, CRP flare response, immune checkpoint blockade, biomarker, immunotherapy

Zhaobing Pan,1– 3,&ast; Qiaoshan Yang,1– 3,&ast; Xiaojing Zhang,1– 3 Xiaoqing Xu,1– 3 Yao Sun,1– 3 Fusheng Zhou,1– 4 Leilei Wen1– 3 1Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Institute of Dermatology, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, People’s Republic of China; 4Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fusheng Zhou; Leilei Wen, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230000, Anhui, People’s Republic of China, Tel +86-138-5698-5934 ; +86-183-5609-9275, Fax +86-0551-63633742, Email biozhoufs@163.com; wenleilei_2012@163.comPurpose: Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by the involvement of multiple organs and the production of antinuclear antibodies. This study aimed to investigate the molecular mechanism of SLE.Patients and Methods: We retrieved genome-wide gene expression levels from five public datasets with relatively large sample sizes from the Gene Expression Omnibus (GEO), and we compared the expression profiles of peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls (HCs). The expression of seven target genes in PBMCs from 25 cases and 3 HCs was further validated by reverse-transcription quantitative PCR (RT‒qPCR). Flow cytometry was used for verifying the proportion of naive CD4(+) T cells and M2 macrophages in PBMCs from 5 cases and 4 HCs.Results: We found 14 genes (TRIM5, FAM8A1, SHFL, LHFPL2, PARP14, IFIT5, PARP12, DDX60, IRF7, IF144, OAS1, OAS3, RHBDF2, and RSAD2) that were differentially expressed among all five datasets. The heterogeneity test under the fixed effect model showed no obvious heterogeneity of TRIM5, FAM8A1, and SHFL across different populations. TRIM5 was positively correlated with the remaining 13 genes. By separating patient samples into TRIM5-high and TRIM5-low groups, we found that up-regulated genes in the TRIM5-high group were mainly enriched in virus-related pathways. Immune cell proportion analysis and flow cytometry revealed that naive CD4(+) T cells were significantly decreased while M2 macrophages were increased in the SLE group. TRIM5 expression levels were negatively correlated with naive CD4(+) T cells but positively correlated with M2 macrophages.Conclusion: Our data indicated that TRIM5 might be a key factor that modulates SLE etiology, possibly through naive CD4(+) T cells and M2 macrophages.Keywords: differential gene expression analysis, gene, virus, autoimmune disease

Hongtao Cheng,1,2,&ast; Xingwen Deng,3,&ast; Jieyao Li,4,&ast; Yonglan Tang,1,2 Shiqi Yuan,5 Xiaxuan Huang,5 Zichen Wang,1 Fuling Zhou,6 Jun Lyu1,7 1Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2School of Nursing, Jinan University, Guangzhou, People’s Republic of China; 3Department of Medical Information, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 4Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 6Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Lyu, Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China, Email lyujun2020@jnu.edu.cn Fuling Zhou, Department of Hematology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan, 430071, People’s Republic of China, Email zhoufuling@whu.edu.cnBackground: Dysphagia is common in elderly patients with dementia and is one of the common clinical geriatric syndromes. It imposes a heavy burden on patients and their caregivers and is becoming an important public health problem. This study examined the association between dysphagia in older dementia patients in the ICU and the subsequent adverse health outcomes they experience.Patients and Methods: A retrospective analysis of adults (≥ 65 years) with dementia in ICUs of a Boston tertiary academic medical center was conducted. Using the International Classification of Diseases’ Ninth and Tenth Revisions, dementia patients were identified. The study cohort comprised 1009 patients, median age 84.82 years, 56.6% female, predominantly White (72.9%). Patients were grouped based on swallowing function: dysphagia (n=282) and no-dysphagia (n=727). Dysphagia was identified via positive bedside swallowing screening. Primary outcomes were 90- and 180-day mortality, secondary outcomes included aspiration pneumonia, pressure injury, and delirium. Cohort characteristics were compared using the Wilcoxon rank-sum and chi-square tests. Dysphagia and outcomes correlations were examined via Kaplan-Meier survival analysis, Cox proportional-hazards regression models, logistic regression models, and subgroup analysis.Results: After adjusting for covariates, the results from multivariate Cox proportional-hazards regression indicated that dysphagia was significantly associated with increased 90-day (HR=1.36, 95% CI=1.07– 1.73, E-value=1.78) and 180-day (HR=1.47, 95% CI=1.18– 1.82, E-value=1.94) mortality; the multifactorial logistic regression results indicated that dysphagia was associated with significant increases in pressure injury (OR=1.58, 95% CI=1.11– 2.23, E-value=1.83) and aspiration pneumonia occurrence (OR=4.04, 95% CI=2.72– 6.01, E-value=7.54), but was not significantly associated with delirium prevalence (OR=1.27, 95% CI=0.93– 1.74).Conclusion: Dysphagia is likely to increase the risk of adverse health outcomes in older adults with dementia in ICU, and these adverse outcomes mostly include 90- and 180-day mortality, aspiration pneumonia, and pressure injury.Keywords: dysphagia, dementia, older adults, mortality, intensive care unit, delirium

Kaili Li, Xiaoxue Hu, Quanyi Lu, Heng Zhang, Jiayi Zhou, Shijing Tian, Fachun Zhou Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Shijing Tian; Fachun Zhou, Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical, University, 1 Youyi Road, Yuzhong Qu, 3rd Floor, Building 1, Chongqing, People’s Republic of China, Tel +23-89011756, Email doctortianshijing@163.com; cyzfc1966@126.comBackground: To evaluate the risk factors and prognosis of patients with acute cholangitis recurrence.Methods: A total of 503 patients with acute cholangitis admitted to the First Affiliated Hospital of Chongqing Medical University between July 2013 and January 2022 were included in this retrospective observational study, who were followed up for 360 days and divided into relapse group and non-recurrence group according to the recurrence of acute cholangitis. Risk factors and prognosis of patients with acute cholangitis recurrence were analyzed by univariate, multivariate analyses and proportional hazards model.Results: A total of 161 patients with recurrent acute cholangitis were identified. Recurrent acute cholangitis usually occurred within 125 days; Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis, and Enterococcus faecium was the most common positive record both in blood and bile culture. In the multivariate analysis, abdominal pain (OR = 2.448, 95% CI = 1.196– 5.010, P = 0.014), bile stones (OR = 2.429, 95% CI = 1.024– 5.762, P = 0.044), diabetes (OR = 1.790, 95% CI = 1.007– 3.182, P = 0.047), pathogen (OR = 3.305, 95% CI = 1.932– 5.654, P< 0.001), and chronic kidney disease (OR = 2.500, 95% CI = 1.197– 5.221, P = 0.015) may be ascertained as the risk factors of acute cholangitis recurrence. The recurrence of acute cholangitis was identified as an independent risk factor for patient death (HR = 4.524, 95% CI = 1.426– 14.357, P = 0.010) by Cox proportional-hazards regression.Conclusion: Abdominal pain, bile stones, diabetes and chronic kidney disease may be risk factors of acute cholangitis recurrence. Patients with recurrent acute cholangitis have poor prognosis and high mortality. Early control of recurrent risk factors and active intervention are beneficial to high-risk patients.Keywords: recurrence, acute cholangitis, risk factors, prognosis

Chengbo Lu,1,&ast; Fanghui Zhou,2,&ast; Huimin Xian,3,&ast; Siyuan Sun,4 Jingkun Yue,4 Ying Zhang,5 Qi Zhao,6 Xing Luo,3 Yang Li7 1Department of Cardiology, 1st Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang, People’s Republic of China; 2Department of Hematology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 3Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 4Department of Cardiology, People’s Hospital of Taihe County, Taihe, Anhui, People’s Republic of China; 5Department of Gynaecology and Obstetrics, 1st Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang, People’s Republic of China; 6Department of Cardiology, 1st Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 7Department of Cardiology, 4th Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing Luo; Yang Li, Email luoxing321@163.com; jacksonbiotechlab@gmail.comBackground: The relationship between serum IL-38 and major adverse cardiovascular events (MACE) in patients with ST elevation myocardial infarction (STEMI) remains unclear.Methods: In the present study, 589 STEMI patients were included, the serum level of IL-38 was measured. The median follow-up time was 720 days, the STEMI patients were divided into high IL-38 (IL-38> 6.49ng/mL) and low IL-38 groups (IL-38≤ 6.49ng/mL) to compare the probability of MACE.Results: Plasma IL-38 levels were significantly lower in STEMI patients than in SAP patients (4.0± 2.2 vs 6.9± 3.2 ng/mL, P < 0.001). Ninety-three STEMI patients met the defined MACE study endpoint. The incidence of MACE was significantly lower in patients with high IL-38 group than in patients with low IL-38 group (7.8% vs 23.7%, P < 0.001). Low plasma IL-38 levels were independently associated with the occurrence of MACE (OR = 0.90, P < 0.001).Conclusion: We get a conclusion that low plasma levels of IL-38 are independently associated with the occurrence of MACE.Graphical Abstract: Keywords: inflammatory response, SAP, IL-38, STEMI, MACE

Qi Zhao,1,&ast; Siyuan Sun,2,&ast; Fanghui Zhou,3,&ast; Jingkun Yue,2 Xing Luo,4 Xiufen Qu1 1Department of Cardiology, 1st Affiliated Hospital of Harbin Medical University, Harbin, 150086, People’s Republic of China; 2Department of Cardiology, People’s Hospital of Taihe County, Taihe, Anhui, 236600, People’s Republic of China; 3Department of Hematology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China; 4Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing Luo; Xiufen Qu, Email luoxing321@163.com; quxiufenhmu@126.comPurpose: The effects of combing evolocumab and statin on the clinical outcome and physiological function of coronary arteries in STEMI patients with non-infarct-related artery (NIRA) disease are still unclear.Methods: A total of 355 STEMI patients with NIRA were enrolled in this study, who underwent combined quantitative flow ratio (QFR) at baseline and after 12 months of treatment with statin monotherapy or statin plus evolocumab.Results: Diameter stenosis and lesion length were significantly lower in the group undergoing statin plus evolocumab. While the group exhibited significantly higher minimum lumen diameter (MLD), and QFR values. Statin plus evolocumab (OR = 0.350; 95% CI: 0.149– 0.824; P = 0.016) and plaque lesion length (OR = 1.223; 95% CI: 1.102– 1.457; P = 0.033) were independently associated with rehospitalization for unstable angina (UA) within 12 months.Conclusion: Evolocumab combined with statin therapy can significantly improve the anatomical and physiological function of the coronary arteries and downregulate the re-hospitalization rate due to UA in STEMI patients with NIRA.Keywords: PCSK9 inhibition, C-reactive protein, inflammation, physiological assessment, quantitative flow ratio, non-infarct-related artery

Yeting Zhou, Leiming Wang, Fei Zhou Xuzhou Medical University Jiangsu Key Laboratory of Tumor Biotherapy, Shuyang People’s Hospital, Suqian, 221000, People’s Republic of ChinaCorrespondence: Leiming Wang; Fei Zhou, Xuzhou Medical University Jiangsu Key Laboratory of Tumor Biotherapy, Shuyang People’s Hospital, Shuyang, Suqian, 221000, People’s Republic of China, Email wangleiming89@21cn.com; zhoufei67a@126.comObjective: Various studies have shown an association between the anti-cancer drug 5-fluorouracil and matrix metalloproteinase 7 (MMP7). The expression of MMP7 in the serum of colorectal cancer patients, as well as their sensitivity to chemotherapy, were examined using the FOLFOX4 chemotherapy treatment.Methods: Serum samples were taken from 216 colorectal cancer patients who had undergone four cycles of gemcitabine and cisplatin treatment. The sera of 216 healthy persons were used as controls. MMP7 levels in the serum were measured by ELISA. Demographic and survival data were collected.Results: MMP7 levels were not associated with sex, age, peritoneal dissemination, liver metastasis, lymph node metastasis, lymphatic invasion, or venous invasion in CRC patients, but were associated with histological grade, tumor size, TNM stage, and depth of tumor invasion. Patients’ serum MMP7 expression reduced after treatment. MMP7 expression was significantly lower chemotherapy-sensitive patients compared with chemotherapy-resistant patients. Elevated MMP7 expression was associated with worse prognosis and chemotherapy-sensitive patients had markedly better overall survival compared with chemotherapy-resistant patients.Conclusion: MMP7 expression was potentially associated with the development of colorectal cancer and elevated levels were associated with chemoresistance in CRC patients. Serum MMP7 levels can be used to screen for drug resistance during FOLFOX4 chemotherapy treatment.Keywords: MMP7, colorectal cancer, FOLFOX4 chemotherapy, chemotherapy-resistant

Hua Wu,1 Xiaojun Zhou,1 Fan Zhou,2 Dongliang Huang,3 Tao Huang1 1Department of Laboratory Medicine, Hainan General Hospital, Affiliated Hainan Hospital of Hainan Medical College, Haikou, People’s Republic of China; 2International School of Public Health and One Health, Hainan Medical University, Haikou, People’s Republic of China; 3Emergency Department, Armed Police Hospital of Hainan, Haikou, People’s Republic of ChinaCorrespondence: Tao Huang, Department of Laboratory Medicine, Hainan General Hospital, Affiliated Hainan Hospital of Hainan Medical College, No. 19, Xiuhua Road, Xiuying District, Haikou, 570311, People’s Republic of China, Tel +868986842560, Email 13005080993@163.comAbstract: DL96 Microbial Identification/Antimicrobial Susceptibility Testing (ID/AST) System (Zhuhai DL, Guangdong, China) is one of the most commonly used commercial ID/AST System in China. This study aims to evaluate the performance of DL 96E for Antimicrobial Susceptibility Testing (AST) of 270 Enterobacterales isolates from Hainan general hospital using the broth microdilution method (BMD) as reference method. CLSI M52 criteria was followed when analyzing the evaluation results. Twenty antimicrobial agents were evaluated, and categorical agreement (CA) ranged from 62.8% to 96.5%. Imipenem had the lowest CA (63.9%) and highest very major errors (VME) (52.8%). A total of 103 carbapenem-resistant Enterobacterales were evaluated; DL 96E miss identified 22 isolates, including six carbapenemase-producing Enterobacteriaceae. DL 96E must adjust the Minimum Inhibitory Concentration (MIC) ranges of ciprofloxacin, levofloxacin, and piperacillin-tazobactam to cover Clinical and Laboratory Standards Institute (CLSI) breakpoints, adjust the formulation of some antimicrobial, such as imipenem, and increase the MIC detection range to cover the Quality control (QC) strains’ MIC range.Keywords: antimicrobial susceptibility testing, broth microdilution method, minimum inhibitory concentration, categorical agreement

Wenwen Sun,1,2 Yuling Xing,2 Fei Zhou,2,3 Yingao Ma,2,3 Xiaozheng Wan,2,4 Huijuan Ma3,5 1Graduate School of North China University of Science and Technology, Tangshan, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Graduate School of Hebei North University, Zhangjiakou, People’s Republic of China; 5Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Huijuan Ma, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel +86 18032838686, Email huijuanma76@163.comObjective: In view of the high prevalence of osteoporosis in diabetic patients, this study aimed to investigate the correlation between TyG-BMI, which represents insulin resistance, and bone loss markers, which represent bone metabolism, in an attempt to provide new ideas for the early prevention and diagnosis of osteoporosis in patients with T2DM.Patients and Methods: A total of 1148 T2DM were enrolled. The clinical data and laboratory indicators of the patients were collected. TyG-BMI was calculated based on fasting blood glucose (FBG), triglycerides (TG), and body mass index (BMI) levels. Patients were divided into Q1-Q4 groups according to TyG-BMI quartiles. According to gender, two groups were divided into men and postmenopausal women. Subgroup analysis was performed according to age, course of disease, BMI, TG level and 25(OH)D3 level. The correlation between TyG-BMI and BTMs was investigated by correlation analysis and multiple linear regression analysis using SPSS25.0 statistical software.Results: 1. Compared with Q1 group, the proportion of OC, PINP and β-CTX in Q2, Q3 and Q4 groups decreased significantly. 2. Correlation analysis and multiple linear regression analysis showed that TYG-BMI was negatively correlated with OC, PINP and β-CTX in all patients and male patients. In postmenopausal women, TyG-BMI was negatively correlated with OC and β-CTX, but not with PINP. 3. Subgroup analysis of male patients and postmenopausal female patients according to age, course of disease, BMI, TG and 25(OH)D3 showed that TyG-BMI had a stronger negative correlation with BTMs in male patients with age < 65, disease duration < 10, BMI≥ 24, TG < 1.7, and 25(OH)D3≥ 20.Conclusion: This study was the first to show an inverse association between TyG-BMI and BTMs in T2DM patients, suggesting that high TyG-BMI may be associated with impaired bone turnover.Keywords: type 2 diabetes mellitus, triglyceride glucose-body mass index, bone turnover markers, inflammation

Weikang Shi,1,2,&ast; Yuwen Lu,1,&ast; Fangyan Zhou,1 Huiyi He,3 Jicong Jiang,1 Ximao Xue1 1Department of Dermatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Dermatology, Jinhua Maternal & Child Health Care Hospital, Jinhua, People’s Republic of China; 3Department of Dermatology, Ruian People’s Hospital, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ximao Xue, Email xueximao2021@163.comAbstract: Eosinophilic pustular folliculitis (EPF) is a rare, chronic, itchy, aseptic disease. Although most cases of infantile EPF (I-EPF) are detected in infants, we found that a 7-year-old child with I-EPF, who received treatment with oral azithromycin in combination with topical narrow bound Ultra Violet B light (NB-UVB) irradiation, with no recurrence at follow-up. Our experience with the successful treatment of this patient can provide a reference for more pediatric patients.Keywords: infantile eosinophilic pustular folliculitis, case report, treatment, dermatopathology

Wei Ju,1,2,&ast; Guan-fa Luo,1,&ast; Yuan-yuan Shi,3 Fei-jun Zhou,1 Meng-qi Li,1 Jian-hui Xu,1 Zhi-xin Yan,2 Xi-hu Yang1 1Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China; 2Department of Burn and Plastic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi-hu Yang, Email yangxihu1981@126.comObjective: Sebaceous carcinoma (SC) of the submandibular gland is extremely rare. Owing to the low morbidity and nonspecific clinical manifestations, diagnosis is commonly delayed, which increases metastasis and mortality. To date, there have been five reported cases of SC of the submandibular gland. Here, we present a new case and review the relevant literature.Methods and Results: A 36-year-old woman presented with an enlarged left submandibular gland. Clinical features included a non-tender solitary nodular mass with normal overlying skin. There were no special findings on computed tomography or ultrasound examination except for a swollen mass in the left submandibular gland. The patient underwent surgical resection. Pathological examination confirmed the diagnosis of SC with nerve infiltration. Immunohistochemical examination of this case showed positive staining for P63, P40, CK7, CK8/18, MLH1, MSH2, MSH6, and PMS2. The specimen was negative for androgen receptor, CEA, S-100, CK5/6, SOX-10, SOX-11, SMA, and GCDFP-15. The KI-67 labeling index was determined to be 15%. PAS and anti-epithelial membrane antigen were positive in partial area. The patient is still undergoing follow-up, and no metastasis or recurrence has been observed for 2 months.Conclusion: This case highlighted the fact that despite its rarity, SC should be considered as a differential diagnosis for masses located in the head and face. Early and accurate diagnosis, followed by wide surgical excision, has a favorable prognosis. Therefore, clinicians should be familiar with the clinical and pathological features of this disease.Keywords: sebaceous carcinoma, salivary gland neoplasms, submandibular gland, androgen receptor, P63, P40

Yuwen Lu, Fangyan Zhou, Yu Gao, Wanwan Jin Department of Dermatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Yu Gao; Wanwan Jin, Email gaoyu0570@sina.com; jinwanwan0604@163.comPurpose: We used color Doppler ultrasound to conduct an objective evaluation of the 595-nm Pulsed Dye Laser (PDL) combined with 755-nm long-pulse alexandrite sequential laser treatment for hybrid IH.Patients and Methods: A total of 116 cases of hybrid IH were selected for this study. The interval between laser treatments was around 4 weeks, and 6 laser treatments or complete removal of the tumor was the end point. All children underwent color Doppler ultrasonography at the 0th, 1st, 6th months of treatment. Children were grouped by gender, age (< 6 months, ≥ 6 months), thickness (< 8 mm, ≥ 8 mm), and location (face and neck, trunk, and extremities). Calculate the volume of IHs according to color Doppler ultrasound. The volume ratio before and after treatment was defined as the A-value. Treatment outcomes were defined as effective when the A-value < 75%.Results: In total, 74 cases (63.79%) had effective outcomes. Overall, the samples showed a statistically significant difference in the reduction of IH volume after 6 months of laser treatment (P < 0.001). The treatment of < 6 months group had better efficacy than the ≥ 6 months group (P < 0.001), the treatment of thickness < 8 mm group had better efficacy than the thickness ≥ 8 mm group (P < 0.001) and there was no significant difference in efficacy between the three different location groups (P > 0.05). Greater reduction in blood flow in the group with the effective outcome than in the group with the ineffective outcome (P < 0.001).Conclusion: Color Doppler ultrasound can be applied to the diagnosis of hybrid IH and to the evaluation of treatment time and outcomes, and it can help clinicians recognize hybrid IH with greater accuracy. The earlier intervention for hybrid IH we perform, the better outcomes will be.Keywords: hybrid infantile hemangioma, color Doppler ultrasound, treatment, pulsed dye laser, alexandrite laser

Kaili Li, Sanle Jiang, Hongxue Fu, Yingting Hao, Shijing Tian, Fachun Zhou Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Shijing Tian; Fachun Zhou, Emergency Department, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong Qu, 17th Floor, Building 1, Chongqing, People’s Republic of China, Tel +86 023-89011756, Email doctortianshijing@163.com; cyzfc1966@126.com; zfc88@126.comBackground: To identify the risk factors and prognosis of carbapenem-resistant organisms (CRO) in patients with acute cholangitis.Methods: This retrospective observational study was conducted to explore the risk factors and prognosis of CRO infection in 503 acute cholangitis patients diagnosed between July 2013 and January 2022 at the First Affiliated Hospital of Chongqing Medical University, who were divided into a CRO group and non-CRO group based on the presence or absence of CRO. Univariate, multivariate analyses, and the proportional hazards model were used to compare the risk factors and prognosis of CRO suffering in patients with acute cholangitis.Results: We identified 35 patients colonized with CRO from 503 acute cholangitis patients. In the multivariate analysis, tumor (OR=7.09, 95% CI=1.11– 45.30, P=0.038) and chronic kidney disease (OR=8.70, 95% CI=2.11– 35.88, P=0.003) were ascertained as the risk factors of the occurrence on CRO infection under the background of acute cholangitis. CRO infection was identified as an independent risk factor for acute cholangitis patient death (HR=5.147, 95% CI=1.475– 17.595, P=0.01) by Cox proportional-hazards regression.Conclusion: Tumor and chronic kidney disease may be risk factors for CRO infection. Patients diagnosed with acute cholangitis further infected with CRO had a poor prognosis and a more severe mortality. Active screening for CRO is expected to facilitate early prevention, diagnosis, and treatment of high-risk patients.Keywords: CRO, acute cholangitis, risk factors, prognosis

Ling Zhang1 &ast;, Xinhua Xie2 &ast;, Yangyan Sun1 &ast;, Futao Zhou1 1School of Basic Medicine, Gannan Medical University, Ganzhou, People’s Republic of China; 2Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Futao Zhou, School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi Province, 341000, People’s Republic of China, Email zhft522@163.comObjective: Hyperhomocysteinemia (HHcy), as an important risk factor for Alzheimer’s disease (AD), would aggravate cognitive dysfunction. This study aimed to investigate whether and to what degree the homocysteine (Hcy) levels in blood and cerebrospinal fluid (CSF) were elevated in AD patients compared with healthy controls and to explore the factors related to the elevated Hcy levels in AD patients.Methods: PubMed and Embase databases were searched to identify eligible studies, and study quality was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Ratio of mean (RoM) Hcy concentrations was used as a measure of fold-change between AD patients and healthy control subjects.Results: We identified 35 eligible studies, consisting a total of 2172 patients with AD and 2289 healthy controls. The pooled results showed that patients with AD had a significantly higher blood level of Hcy (RoM, 1.32; 95% CI, 1.25– 1.40; p< 0.001) than controls did, with large heterogeneity across studies (I2=81.4%, p< 0.001). Hcy level in CSF did not differ significantly between patients with AD than controls (RoM, 1.12; 95% CI, 0.90– 1.39, p=0.293; I2=69.4%, p=0.02). A random effects meta-regression analysis revealed that there was an inverse correlation between the blood levels of Hcy and folate (p=0.006). There was no link found between the blood levels of vitamin B12, or the Mini-Mental Status Examination scores reflecting the degree of cognitive impairment, and blood levels of Hcy.Conclusion: Regardless of dementia severity, there is an approximate one-third increase in blood Hcy in AD patients, which is robustly associated with a decreased level of blood folate in AD, but not with that of blood vitamin B12 nor the degree of dementia. Future investigation on the cause-and-effect link between Hcy and folate is warranted to clarify this issue.Keywords: homocysteine, Alzheimer’s disease, meta-regression

Teesha Downton,1,2 Fiona Zhou,1,2 Davendra Segara,1 Rinath Jeselsohn,3,&ast; Elgene Lim1,2,&ast; 1Garvan Institute of Medical Research, Sydney, NSW, Australia; 2School of Clinical Medicine, St Vincent’s Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia; 3Dana-Farber Cancer Institute, Boston, MA, USA&ast;These authors contributed equally to this workCorrespondence: Elgene Lim, Tel +61 2 9355 5600, Fax +61 2 9355 5602, Email e.lim@garvan.org.auAbstract: Several endocrine therapies are currently available for the treatment of estrogen receptor (ER) positive breast cancer, but the clinical benefit of these agents is limited by endocrine therapy drug resistance. A common mechanism of endocrine therapy resistance is ESR1 mutations. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has activity against ESR1 mutant tumors but requires intramuscular injection and has poor bioavailability that precludes optimal drug dosing. This led to the development of second-generation SERDs which are potent and have improved oral bioavailability and pharmacokinetics. Several of these oral SERDs are now in phase III trials in both the early and advanced ER positive breast cancer settings. This review summarizes the background of oral SERD development, the current status and future perspectives.Keywords: selective estrogen receptor degraders, breast cancer, estrogen receptor

Weiyuan Ma,1 Ruyu Zhan,2 Changlin Sui,3 Fushan Zhou,2 Haidong Liu,4 Xiuwen Zhang,5 Zhenqiang Ruan,6 Yukun Wang,7 Xiaolan Cai8 1Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Scientific Research Center, Anxi County Hospital, Quanzhou, Fujian, People’s Republic of China; 3Department of Dermatology, Yantai Yuhuangding Hospital, Yantai, Shandong, People’s Republic of China; 4Department of Dermatology, Liaocheng People’s Hospital, Liaocheng, Shandong, People’s Republic of China; 5Department of Dermatology, Weihai Municipal Hospital, Weihai, Shandong, People’s Republic of China; 6Department of Dermatology, Jinan Dermatosis Prevention and Control Hospital, Jinan, Shandong, People’s Republic of China; 7Department of Dermatology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 8Department of Otolaryngology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Weiyuan Ma, Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China, Email fymaweiyuan@wfmc.edu.cnPurpose: The clinical and pathological data of patients with rhinofacial ulcers were retrospectively reviewed and analyzed to lay the foundation for standardized clinical treatment.Patients and Methods: We retrospectively analyzed the clinical data, etiology, pathological features, treatment methods, and prognosis of 243 patients with rhinofacial ulcers treated in the Departments of Otorhinolaryngology and Dermatology at six hospitals in Shandong Province, China from July 2014 to October 2021. The clinical characteristics and treatment methods of the rhinofacial ulcers were summarized to provide a basis for standardizing patients’ diagnosis and treatment.Results: The male-to-female ratio of the 243 patients was 2.04:1, and their ages ranged from 25 to 91 years. The most common sites were the cheek, nasal dorsum, and upper lip. The common primary diseases were basal-cell carcinoma, squamous-cell carcinoma, and odontogenic fistula, but rare triggers played important roles in some cases, such as infection, autoimmune diseases, and adverse drug reactions. Surgical treatment was feasible for tumor ulcers; 71 patients with basal-cell carcinoma and 50 with squamous-cell carcinoma were treated with Mohs micrographic surgery. During the follow-up period of 1– 84 months, most of the rhinofacial ulcers were cured, while natural killer/T-cell lymphoma, angiosarcoma, and melanoma were important causes of death.Conclusion: Various causes may lead to rhinofacial skin ulcers, and some cases lacking specificity of clinical manifestations are easily misdiagnosed in clinical practice. Histopathological biopsy is valuable for confirming the diagnosis, after which correct etiological treatment is very important.Keywords: skin, diagnosis, treatment, otorhinolaryngology, dermatology

Zejun Wang,1,&ast; Shichao Zhang,2,&ast; Chaochao Zheng,3 Kaide Xia,4 Liangquan Sun,4 Xuejie Tang,4 Fulin Zhou,4 Yan Ouyang,2 Fuzhou Tang3 1Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 2Key Laboratory of Infectious Immune and Antibody Engineering in Guizhou Province/School of Biology and Engineering, Guizhou Medical University, Guiyang, People’s Republic of China; 3Immune Cells and Antibody Engineering Research Center of Guizhou province/School of Biology and Engineering, Guizhou Medical University, Guiyang, People’s Republic of China; 4Guiyang Maternal and Child Health Care Hospital, Guiyang Children’s Hospital, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fuzhou Tang, Immune Cells and Antibody Engineering Research Center of Guizhou province/School of Biology and Engineering, Guizhou Medical University, Guiyang, People’s Republic of China, Tel +86 085188174043, Email tangfuzhou@163.com Yan Ouyang, Key Laboratory of Infectious Immune and Antibody Engineering in Guizhou province/School of Biology and Engineering, Guizhou Medical University, Guiyang, People’s Republic of China, Email ouyangyan@gmc.edu.cnBackground: Tumor immune cell infiltration is closely associated with the occurrence and development of tumors. Collagen triple helix repeats containing 1 (CTHRC1), a regulator of collagen expression and cell migration, is involved in the metastasis and invasion of tumors. However, the role of CTHRC1 in breast cancer remains unclear. This study aimed to investigate the prognostic value of CTHRC1, and further explore its association with immune infiltration in breast cancer.Methods: CTHRC1 expression pattern and prognostic value were analyzed using ONCOMINE, PrognoScan, GEPIA, and Kaplan–Meier Plotter databases. We then detected CTHRC1 mRNA levels in breast cancer tissues and paired normal breast tissues by Q-PCR. Subsequently, the University of California Santa Cruz (UCSC) database was used to determine the methylation status of CTHRC1. Furthermore, CTHRC1 mutations were investigated using the Catalogue of Somatic mutations in Cancer (COSMIC) and cBioPortal databases. We also assessed the correlation between CTHRC1 expression and immune cell infiltration using TIMER. In addition, The relationship of CTHRC1 expression with the immune marker sets of various immune cells was evaluated using GEPIA and TIMER.Results: CTHRC1 was highly expressed in a variety of tumors, including breast cancer. Elevated CTHRC1 expression was related to a poor prognosis. Notably, CTHRC1 expression was significantly associated with macrophage infiltration, especially the immune infiltration gene marker set of M2. Copy number variations, DNA mutations and methylation states might be potential mechanisms for regulating CTHRC1 expression. Protein digestion and absorption, human papillomavirus infection, ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways were identified as the potential CTHRC1-driven signaling pathways.Conclusion: These findings suggest that CTHRC1 could be a promising immune-related biomarker for the treatment of breast cancer patients.Keywords: CTHRC1, breast cancer, prognostic, macrophage, biomarker

Tao Luo,1 Yile Wang,1 Hailin Tang,1 Fei Zhou,2 Ying Chen,3 Bing Pei,4 Jinke Wang1 1State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, People’s Republic of China; 2School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, 521041, People’s Republic of China; 3School of Medical Technology, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 4Department of Clinical Laboratory, the Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian, Jiangsu, 223800, People’s Republic of ChinaCorrespondence: Jinke Wang, State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, People’s Republic of China, Email wangjinke@seu.edu.cnBackground: The inflammatory diseases pose a great threat to human health. Variant anti-inflammatory agents have been therefore developed. However, the current anti-inflammatory drugs are still challenged by low response and side effects. There remain great unmet treatments to inflammatory diseases.Methods: In this work, we fabricate a recombinant adeno-associated virus (rAAV), rAAV-DMP-miR533, by packaging a DNA molecule DMP-miR533 into AAV, in which DMP is a NF-κB-activatable promoter composed of a NF-κB decoy and a minimal promoter and miR533 codes an artificial microRNA targeting NF-κB RELA. We evaluate the in vitro and in vivo anti-inflammatory effect of the virus with inflammatory cells and the mice of three typical inflammatory diseases including the dextran sulphate sodium-induced acute colitis, imiquimod-induced psoriasis, and collagen-induced arthritis.Results: We found that rAAV-DMP-miR533 had marked anti-inflammatory effect in both cells and mice. In addition, rAAV-DMP-miR533 showed biosafety in mice.Conclusion: This study thus provides a promising gene therapy to variant inflammatory diseases by directly targeting NF-κB, an established hub regulator of inflammation.Keywords: NF-κB, inflammation, therapy, AAV, microRNA

Luo Y, Liu F, Yan C, et al. Cancer Manag Res. 2020;12:2195–2207. We, the Editor and Publisher of Cancer Management and Therapy are retracting the published article. Since publication, concerns have been raised about the duplication of images in this article with those from other unrelated articles. Specifically, The image from Figure 2D, A498, si-NC, has been duplicated with the image from Figure 4C, C-33A, agomir-NC from Wu F, Sui Y, Wang Y, Xu T, Fan L, Zhu H. Long Noncoding RNA SNHG7, a Molecular Sponge for microRNA-485, Promotes the Aggressive Behavior of Cervical Cancer by Regulating PAK4. Onco Targets Ther. 2020;13:685–699. https://doi.org/10.2147/OTT.S232542 (RETRACTED). The image from Figure 5C, 786-O, si-NC, has been duplicated with the image from Figure 2D, H460, si-NC from Dai J, Wang B, Zhao Y, et al. RETRACTED ARTICLE: Long Noncoding RNA LINC01426 Sequesters microRNA-519d-5p to Promote Non-Small Cell Lung Cancer Progression by Increasing ETS1 Expression. Cancer Manag Res. 2020;12:12697–12708. https://doi.org/10.2147/CMAR.S277113 (RETRACTED). The image from Figure 5C, 786-O, si-CASC19+miR-532 inhibitor, and Figure 6E, 786-O, si-CASC19+pcDNA3.1-ETS1 has been duplicated with the image from Figure 6D, A549, agomiR-NC, and Figure 6E, A549, agomiR-NC, respectively, from Kang X, Kong F, Wu S, et al. microRNA-612 suppresses the malignant development of non-small-cell lung cancer by directly targeting bromodomain-containing protein 4. Onco Targets Ther. 2019;12:4167–4179. https://doi.org/10.2147/OTT.S204004 (RETRACTED). The image from Figure 5D, 786-O, si-CASC19+NC inhibitor, has been duplicated with the image from Figure 6F, Hep3B, 2, from Yun Z, Meng F, Jiang P, Yue M, Li S. microRNA-548b suppresses aggressive phenotypes of hepatocellular carcinoma by directly targeting high-mobility group box 1 mRNA. Cancer Manag Res. 2019;11:5821–5834.https://doi.org/10.2147/CMAR.S198615 (RETRACTED).The image from Figure 5D, A498, si-NC, has been duplicated with the image from Figure 5D, CAOV-3, miR-control from Li C, Yu S, Wu S, Ni Y, Pan Z. MicroRNA-936 targets FGF2 to inhibit epithelial ovarian cancer aggressiveness by deactivating the PI3K/Akt pathway. Onco Targets Ther. 2019;12:5311–5322. https://doi.org/10.2147/OTT.S213231 (RETRACTED) and Figure 5d, TPC-1, si-LINC00520+antagomir-577, from Sun Y, Shi T, Ma Y, Qin H, Li K. RETRACTED ARTICLE: Long noncoding RNA LINC00520 accelerates progression of papillary thyroid carcinoma by serving as a competing endogenous RNA of microRNA-577 to increase Sphk2 expression. Cell Cycle. 2020;19(7):787–800. DOI: https://doi.org/10.1080/15384101.2020.1731062 (RETRACTED). The image from Figure 6D, 786-O, si-CASC19+pcDNA3.1-ETS1, has been duplicated with the image from Figure 4D, Migration, HOS, agomir-760, from Yin R, Liu J, Zhao D, Wang F. Long Non-Coding RNA ASB16-AS1 Functions as a miR-760 Sponge to Facilitate the Malignant Phenotype of Osteosarcoma by Increasing HDGF Expression. Onco Targets Ther. 2020;13:2261–2274. https://doi.org/10.2147/OTT.S240022 (RETRACTED). The image from Figure 6E, A498, si-NC, has been duplicated with the image from Figure 2D, Eca109, si-NC, from Gao J, Zhang Z, Su H, Zong L, Li Y. Long Noncoding RNA FGD5-AS1 Acts as a Competing Endogenous RNA on microRNA-383 to Enhance the Malignant Characteristics of Esophageal Squamous Cell Carcinoma by Increasing SP1 Expression. Cancer Manag Res. 2020;12:2265–2278. https://doi.org/10.2147/CMAR.S236576 (RETRACTED). When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient original data from their study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The authors listed in this publication have been informed. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Qinglin Li,1,&ast; Xiaoyan Cai,2,&ast; Guanggang Li,3 Hongyan Ju,3 Dawei Li,4 Feihu Zhou1,5 1Department of Critical Care Medicine, the First Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Nephrology, the Second Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Critical Care Medicine, the Seventh Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China; 4Department of Critical Care Medicine, the Sixth Medical Center, Chinese PLA General Hospital, Beijing, 100048, People’s Republic of China; 5Chinese PLA General Hospital National Clinical Research Center for Geriatric Diseases, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feihu Zhou, Department of Critical Care Medicine, the First Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Tel +86– 10– 66938148, Fax +86– 10– 88219862, Email feihuzhou301@126.comPurpose: Acute kidney injury (AKI) in elderly patients is associated with higher hospital mortality. However, the relationship between AKI and peri-intubation complications is unclear.Methods: This retrospective, observational, multicenter cohort study enrolled 3271 consecutive elderly patients (≥ 75 years) who received invasive mechanical ventilation (MV) in four medical centers of Chinese PLA General Hospital from 2008 to 2020. AKI was diagnosed according to the 2012 KDIGO criteria by an absolute increase in serum creatinine of ≥ 26.5 μmol/L within the first 48 hours of MV. We recorded subsequent in-hospital complications, including incident gastrointestinal bleeding, new-onset electrolyte imbalances, severe hypoxemia, hypoalbuminemia, cardiovascular instability and all-cause 90-day mortality.Results: A total of 1292 patients were included in the final evaluation, with 29.1% presenting AKI (stage 1: 31.4%, stage 2: 35.1%, stage 3: 33.5%). Multiple regression analyses show that more advanced AKI increased the risk of MAP < 65 mmHg (stage 1: OR=1.833, P=0.002; stage 2: OR= 4.653, P< 0.001; stage 3: OR=4.834, P< 0.001) and SBP < 90 mmHg (stage 1: OR=1.644, P=0.014; stage 2: OR=3.701, P< 0.001; stage 3: OR=5.750, P< 0.001), a new need for or requiring an increased dose of vasopressors (stage 1: OR=1.623, P=0.014; stage 2: OR=3.250, P< 0.001; stage 3: OR=12.132, P< 0.001), gastrointestinal bleeding (stage 1: OR=1.102, P=0.669; stage 2: OR=1.471, P=0.060; stage 3: OR=2.377, P< 0.001), severe hypoxia (stage 1: OR=1.213, P=0.399; stage 2: OR=1.449, P=0.077; stage 3: OR=2.214, P< 0.001) and all-cause 90-day mortality (stage 1: OR =0.935; P=0.741; stage 2: OR=1.888; P=0.001; stage 3: OR=12.584; P< 0.001).Conclusion: Our study suggests that the presence of AKI within the first 48 hours of MV in geriatric patients is associated with a higher risk for postintubation complications and 90-day mortality. Moreover, the risk of complications was greater for patients with more severe AKI.Keywords: mechanical ventilation, aged, complications, acute kidney injury, electrolyte imbalance

Xiudi Han,1 Liang Chen,2 Hui Li,3 Fei Zhou,3 Xiqian Xing,4 Chunxiao Zhang,5 Lijun Suo,6 Jinxiang Wang,7 Xuedong Liu,1 Bin Cao3 On behalf of the CAP-China network1Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital Group, Qingdao City, Shandong Province, 266011, People’s Republic of China; 2Department of Infectious Diseases, Nanjing Lishui People’s Hospital, Nanjing City, Jiangsu Province, 211213, People’s Republic of China; 3National Clinical Research Center of Respiratory Diseases, Center for Respiratory Diseases, China-Japan Friendship Hospital; Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, 100020, People’s Republic of China; 4Department of Respiratory Medicine, Yan’an Hospital Affiliated to Kunming Medical University, Kunming City, Yunnan Province, 652199, People’s Republic of China; 5Department of Respiratory Medicine, Beijing Huimin Hospital, Beijing, 100054, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, Zibo Municipal Hospital, Zibo City, Shandong Province, 255000, People’s Republic of China; 7Department of Respiratory Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of ChinaCorrespondence: Xuedong Liu, Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital Group, Jiaozhou Road, Qingdao City, Shandong Province, 266011, People’s Republic of China, Tel +86-18661678256, Fax +86-532-82789055, Email xuedongliu@263.net Bin Cao, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Yinghuayuan East Street, Chao-Yang District, Beijing, 100020, People’s Republic of China, Tel +86-13911318339, Fax +86-10-84206264, Email caobin_ben@163.comBackground: Limited data were available about the burden of cardiovascular events (CVEs) during hospitalization in elderly patients with community-acquired pneumonia (CAP). The aim was to assess the incidence, characteristics, predictive factors and outcomes of CVEs in elderly patients with CAP during hospitalization.Methods: This study was a multicenter, retrospective research on hospitalized elderly patients with CAP from the CAP-China network. Predictive factors for the occurrence of CVEs and 30-day mortality were identified by multivariable logistic regression analysis.Results: Of 2941 hospitalized elderly patients, 402 (13.7%) developed CVEs during hospitalization with the median age of 81 years old. Compared with non-CVEs patients, patients with CVEs were older, more comorbidities, and higher disease severity; use of glucocorticoids, leukocytosis, azotemia, hyponatremia, multilobe infiltration and pleural effusion were more common; the rate of clinical failure (CF), in-hospital mortality and 30-day mortality were higher, which significantly increased with age and the number of CVEs (p < 0.001). Multivariable logistic regression showed previous history of congestive heart failure (odds ratio [OR], 6.16; 95% CI, 4.14– 9.18), CF (OR, 4.69; 95% CI, 3.392– 6.48), previous history of ischemic heart disease (OR, 2.22; 95% CI, 1.61– 3.07), use of glucocorticoids (OR, 2.0; 95% CI, 1.39– 2.89), aspiration (OR, 1.88; 95% CI, 1.26– 2.81), pleural effusion (OR, 1.66; 95% CI, 1.25– 2.20), multilobe infiltration (OR, 1.50; 95% CI, 1.15– 1.96), age (OR, 1.05; 95% CI, 1.04– 1.07), and blood urea nitrogen (OR, 1.03; 95% CI, 1.01– 1.06) were independent predictors for the occurrence of CVEs, while level of blood sodium (OR, 0.98; 95% CI, 0.97– 0.99) was protective factor. Renal failure (OR, 9.46; 95% CI, 4.17– 21.48), respiratory failure (OR, 9.32; 95% CI, 5.91– 14.71), sepsis/septic shock (OR, 7.87; 95% CI, 3.58– 17.31), new cerebrovascular diseases (OR, 5.94; 95% CI, 1.78– 19.87), new heart failure (OR, 4.04; 95% CI, 1.15– 14.14), new arrhythmia (OR, 2.38; 95% CI, 1.11– 5.14), aspiration (OR, 1.95; 95% CI, 1.09– 3.50), CURB-65 (OR, 1.57; 95% CI, 1.21– 2.02), and white blood cell count (OR, 1.05; 95% CI, 1.02– 1.09) were independent predictors for 30-day mortality in elderly patients with CAP, while lymphocyte count (OR, 0.63; 95% CI, 0.46– 0.87) was protective factor.Conclusion: Patients with CVEs had heavier disease burden and worse prognosis. Early recognition of risk factors is meaningful to strengthen the management in elderly patients with CAP.Keywords: community-acquired pneumonia, cardiovascular events, prognostic factors, elderly

Jun Wang,1– 3 Linlin Yang,4 Linquan Yang,4 Fei Zhou,1 Hang Zhao,2 Jing Liu,2 Huijuan Ma,1,2,4,&ast; Guangyao Song1,2,&ast; 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology and Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Emergency, Baoding First Central Hospital, Baoding, Hebei, People’s Republic of China; 4Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huijuan Ma, Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, Hebei, People’s Republic of China, Email huijuanma76@163.com Guangyao Song, Department of Endocrinology and Metabolic Diseases, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, Hebei, People’s Republic of China, Email sguangyao2@163.comPurpose: To investigate changes in the protein expression profile of white adipose tissue in low-birth weight (LBW) mice with high-fat diets using tandem mass tag (TMT) and liquid chromatography-mass spectrometry (LC-MS/MS) and parallel reaction monitoring (PRM).Methods: Institute of Cancer Research (ICR) mice were used to establish an LBW model using malnutrition during pregnancy. Male pups were randomly selected from LBW and normal-birth weight (NBW) offspring, then all given a high-fat diet. Blood glucose, serum insulin, total cholesterol (TC) and triglyceride (TG) levels were measured. The weight ratio of liver, muscle, and adiposity index were calculated. Hematoxylin and eosin staining was used to visualize adipose tissue morphology. Oil red O staining of liver and TG content of muscle were used to determine ectopic lipid deposition. TMT combined with LC-MS/MS was used to analyze protein expression in white adipose tissue. PRM and Western blot were used to verify the expression of CD36, SCD1, PCK1 and PPARγ.Results: Compared with NBW mice, fasting blood glucose, insulin and HOMA-IR significantly increased in LBW mice, indicating insulin resistance and impaired glucose regulation; TC, TG, adipocyte size, and adiposity index were increased in LBW mice, suggesting obesity and disorder of lipid metabolism. We observed ectopic lipid deposition in liver and muscle. There were 996 differentially expressed proteins (DEPs) in the LBW/NBW groups. Peroxisome proliferator-activated receptor (PPAR) was a relatively important signaling pathway regulating metabolic process in functional enrichment analysis of DEPs. Up-regulated expression of CD36, SCD1, and PCK1 in the adipose tissue of LBW mice was observed through PPAR pathways cluster analysis. And PRM and Western blot assay validated the proteomics findings.Conclusion: When exposed to high-fat diets, LBW mice exhibited insulin resistance and disorder of lipid metabolism compared with NBW mice. The expression of PPARγ was elevated, as well as upstream CD36, downstream SCD1 and PCK1 of the PPARγ in the adipose tissue of LBW mice. It was suggested that the activation in CD36/PPARγ/SCD1 and CD36/PPARγ/PCK1 pathways may induce adipose dysfunction, thereby increasing susceptibility to insulin resistance.Keywords: low birth weight, adipose tissue, insulin resistance, lipid metabolism

Yuling Xing,1,2 Tiantian Cheng,1,3 Fei Zhou,1,2 Huijuan Ma1,4,5 1Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China; 2Graduate School of Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 3Department of Internal Medicine, School of Clinical Medicine, North China University of Science and Technology, Tangshan, 063210, Hebei, People’s Republic of China; 4Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital Shijiazhuang, Hebei, 050051, People’s Republic of China; 5Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of ChinaCorrespondence: Huijuan Ma, Email huijuanma19@163.comObjective: To investigate the association between vitamin D deficiency and NAFLD risk in patients with type 2 diabetes mellitus (T2DM).Methods: Overall, 434 patients with T2DM admitted to Hebei General Hospital from January 2019 to December 2019 were selected as the study subjects. According to abdominal ultrasound findings, patients were divided into the NAFLD group and the non-NAFLD group. Participants were divided into two study groups according to the 25-hydroxyvitamin D [25(OH)D] level. 25(OH)D deficiency was defined if 25(OH)D vitamin levels were < 20 ng/mL. Chi-square test and one-way analysis of variance were used to compare groups. The relationship between 25(OH)D and NAFLD risk was analyzed using correlation and regression analyses. Furthermore, subgroup analyses were performed to verify the robustness of the results.Results: The 25(OH)D level in patients with T2DM complicated by NAFLD was significantly lower than in patients with T2DM only. Vitamin D deficiency was highly prevalent among T2DM patients with NAFLD. This study suggested that vitamin D deficiency was an independent factor for developing NAFLD in patients with T2DM. T2DM patients with vitamin D deficiency had 2.045 times higher risk of developing NAFLD than those without vitamin D deficiency. Vitamin D deficiency was associated with high NAFLD preference in T2DM patients with BMI > 23kg/m2, but not those with BMI ≤ 23kg/m2. The significant correlation between vitamin D deficiency and NAFLD was found in participants with BMI > 23kg/m2, age ≤ 65 years, without hypertension, TG < 1.7mmol/l, HDL ≥ 1 mmol/l in men, ≥ 1.3 mmol/l in women, HBA1C ≤ 7%, or females.Conclusion: This study suggests that T2DM people with BMI > 23kg/m2 were more susceptible to NAFLD by vitamin D deficiency and that it is necessary to maintain optimal serum vitamin D levels in this population.Keywords: type 2 diabetes mellitus, non-alcoholic fatty liver disease, vitamin D

Xiaoming Li,1,2 Chao Liu,2 Xiaoli Wang,1 Zhi Mao,2 Hongyu Yi,1 Feihu Zhou2 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, The First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Feihu ZhouCritical Care Medicine, The First Medical Centre, Chinese People’s Liberation Army General Hospital, 28 Fu-Xing Road, Beijing, 100853, People’s Republic of China, Tel +86-10-66938148, Fax +86-10-88219862, Email feihuzhou301@126.comBackground: Sepsis is a systemic inflammatory response due to infection, resulting in organ dysfunction. Timely targeted interventions can improve prognosis. Inflammation plays a crucial role in the process of sepsis. To identify potential sepsis early, we developed and validated a nomogram model and a simple risk scoring model for predicting sepsis in critically ill patients.Methods: The medical records of adult patients admitted to our intensive care unit (ICU) from August 2017 to December 2020 were analyzed. Patients were randomly divided into a training cohort (70%) and a validation cohort (30%). A nomogram model was developed through multivariate logistic regression analysis. The continuous variables included in nomogram model were transformed into dichotomous variables. Then, a multivariable logistic regression analysis was performed based on these dichotomous variables, and the odds ratio (OR) for each variable was used to construct a simple risk scoring model. The receiver operating characteristic curves (ROC) were constructed, and the area under the curve (AUC) was calculated.Results: A total of 2074 patients were enrolled. Finally, white blood cell (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and neutrophil-to-lymphocyte ratio (NLR) were included in our models. The AUC of the nomogram model and the simple risk scoring model were 0.854 and 0.842, respectively. The prediction performance of the two models on sepsis is comparable (p = 0.1298).Conclusion: This study combining five commonly available inflammatory markers (WBC, CRP, IL-6, PCT and NLR) developed a nomogram model and a simple risk scoring model to predict sepsis in critically ill patients. Although the prediction performance of the two models is comparable, the simple risk scoring model may be simpler and more practical for clinicians to identify potential sepsis in critically ill patients at an early stage and strategize treatments.Keywords: nomogram, score, model, prediction, inflammatory marker, sepsis

Yao Wang,1,2 Yujie He,1,2 Yanyan Zhu,1,2 Ting He,1,2 Jie Xu,1,2 Qinmei Kuang,1,2 Yuqi Ji,1,2 Renshi Xu,3 Fangjun Li,4 Fuqing Zhou1,2 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 2Neuroimaging Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang, 330006, People’s Republic of China; 3Department of Neurology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang, 330006, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of ChinaCorrespondence: Fuqing Zhou, Department of Radiology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, People’s Republic of China, Tel +86- 13694881033, Email fq.chou@yahoo.com; ndyfy02301@ncu.edu.cn Fangjun Li, Department of Neurology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, People’s Republic of China, Tel +86- 13576937919, Email fishmonger@126.comObjective: Clinical symptoms such as major defects in energy metabolism may involve the hypothalamus in amyotrophic lateral sclerosis (ALS) patients. Our recent study discovered that the single-nucleotide polymorphisms (SNPs) of rs2619566, rs79609816 and rs10260404 are associated with sporadic ALS (sALS). Thus, this study aims to investigate the hypothalamic functional reorganization and its association with the above polymorphisms risk alleles in sALS patients of Chinese Han ancestry.Methods: Forty-four sALS patients (28 males/16 females) and 40 healthy subjects (HS; 28 males/12 females) underwent resting-state functional MRI, genotyping and clinical assessments. A two-sample t test (P < 0.01, GRF correction at P < 0.05) was performed to compare hypothalamic connectivity for group-level analysis in disease diagnosis and genotype, and then the genotype-diagnosis interaction effect was assessed. Finally, Spearman correlation analyses were performed to assess the relationship between the altered functional connectivity and their clinical characteristics.Results: The sALS patients showed a short disease duration (median = 12 months). Regarding the diagnosis effect, the sALS patients showed widespread hypothalamic hyperconnectivity with the left superior temporal gyrus/middle temporal gyrus, right inferior frontal gyrus, and left precuneus/posterior cingulate gyrus. For the genotype effect of SNPs, hyperconnectivity was observed in only the medial hypothalamus when the sALS patients harboring the minor C allele of rs2619566 in contactin-4 (CNTN4), while the sALS patients with the TT allele showed a hyperconnectivity network in the right lateral hypothalamus. This connectivity pattern was not observed in other SNPs. No significant genotype-diagnosis interaction was found. Moreover, altered functional connectivity was not significantly correlated with clinical characteristics (P : 0.11– 0.90).Conclusion: These results demonstrated widespread hypothalamic hyperconnectivity in sALS. The risk allele C of the CNTN4 gene may therefore influence functional reorganization of the medial hypothalamus. The effects of the CNTN4 rs2619566 polymorphism may exist in the hypothalamic functional connectivity of patients with sALS.Keywords: sporadic amyotrophic lateral sclerosis, hypothalamus, lateral hypothalamus, medial hypothalamus, resting-state functional connectivity

Fei Zhou,1,2,&ast; Ou Dai,1,2,&ast; Cheng Peng,1,2 Liang Xiong,1– 3 Hui Ao,1,4 Fei Liu,1– 3 Qin-Mei Zhou1,3,4 1State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 2School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 3Institute of Innovative Medicine Ingredients of Southwest Specialty Medicinal Materials, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 4Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng Peng; Qin-Mei Zhou Tel +86 28 61800005; +86 28 61800231Email pengchengchengdu@126.com; zhqmyx@sina.cnPurpose: Perilla frutescens (L.) Britt., a traditional edible-medicinal herb in China, has been used to treat cardiovascular and cerebrovascular (cardio-cerebrovascular) diseases for thousands of years. However, knowledge of the mechanisms underlying the effects of essential oil from P. frutescens (EOPF) in the treatment of cardio-cerebrovascular diseases is lacking. The promotion of angiogenesis is beneficial in the treatment of ischemic cardio-cerebrovascular diseases. The current study investigated the pro-angiogenic role of EOPF and its main component perillaldehyde in sunitinib-injured transgenic Tg (flk1:EGFP) zebrafish embryos and human umbilical vein endothelial cells (HUVECs) for the first time.Materials and Methods: The pro-angiogenic effects of EOPF and perillaldehyde were observed in vivo using transgenic Tg (flk1:EGFP) zebrafish embryos and in vitro using HUVECs. Cell viability, proliferation, migration, tube formation, and protein levels were detected by MTT, EdU staining, wound healing, transwell chamber, and Western blot assays, respectively.Results: EOPF and perillaldehyde exerted a significant stimulatory effect on the formation of zebrafish intersegmental vessels (ISVs). Moreover, EOPF and perillaldehyde promoted proliferation, migration, and tube formation in sunitinib-treated HUVECs. Additionally, our findings uncovered that the pro-angiogenic effects of EOPF and perillaldehyde were mediated by increases in the expression ratios of p-ERK1/2 to ERK1/2 and Bcl-2 to Bax.Conclusion: The present study is the first report to provide clear evidence that EOPF and perillaldehyde promote angiogenesis by stimulating repair of sunitinib-injured ISVs in zebrafish embryos and promoting proliferation, migration, and tube formation in sunitinib-injured HUVECs. The underlying mechanisms are related to increased p-ERK1/2 to ERK1/2 and Bcl-2 to Bax expression ratios. EOPF and perillaldehyde may be used in the treatment of cardio-cerebrovascular diseases, which is consistent with the traditional application of P. frutescens.Keywords: Perilla frutescens, essential oil, perillaldehyde, pro-angiogenesis, HUVECs, zebrafish

Tao Zhang,1,&ast; Qin Liu,2,&ast; Yingfan Zhu,1 Songfa Zhang,3 Qiaohua Peng,3 Amanda Louise Strickland,4 Wenxin Zheng,4,5 Feng Zhou2 1Department of Gynecology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pathology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA; 5Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA&ast;These authors contributed equally to this workCorrespondence: Feng ZhouDepartment of Pathology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, 310006, People’s Republic of ChinaTel +86-571-89991702Fax +86-571-87061878Email fungchew@zju.edu.cnPurpose: Programmed death-ligand 1 (PD-L1) has been widely used as a prognostic biomarker and an immunotherapeutic target in numerous cancers, but information on the clinical significance of its expression in endometrial serous carcinoma (ESC) is largely lacking. Here, we evaluate the predictive value of PD-L1 expression in ESC.Materials and Methods: A total of 79 cases of ESC accessioned between January 2003 and September 2015 were selected for further analysis. PD-L1 expression was evaluated in whole tissue sections of these cases by using the tumor proportion score (TPS, cut-off 1%) and combined positive score (CPS, cut-off 1) scoring methods.Results: Overall, there was a heterogeneous expression of PD-L1, focal or patchy, in ESCs. PD-L1 positivity was observed in 43.0% of ESCs by TPS and 73.4% of ESCs by CPS. Kaplan–Meier survival analysis showed that patients with PD-L1-positive tumors suffered significantly worse OS and PFS, when compared with PD-L1 negative tumors (log-rank p = 0.037 and p = 0.003, respectively). In contrast, PD-L1 positivity by CPS within the ESC cases showed no statistical significance for OS and PFS (log-rank p = 0.720 and p = 0.928, respectively). Multivariate Cox analysis showed that PD-L1 positivity by TPS was significantly associated with PFS (HR = 1.921, p = 0.039) but not OS (HR = 1.229, p = 0.631).Conclusion: PD-L1 expression is frequently found in ESC, suggesting a potential role of the PD-1/PD-L1 pathway as a potential therapeutic target for these tumors. PD-L1 expression by TPS also serves as a negative prognostic marker in ESC and implies an unfavorable outcome.Keywords: PD-L1, endometrial serous carcinoma, endometrial cancer, immune therapy

Bing Xu, Mengmeng Yan, Fei Zhou, Desheng Cai, Wenbo Guo, Xiaohui Jia, Runping Liu, Tao Ma, Tong Li, Feng Gao, Penglong Wang, Haimin Lei School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of ChinaCorrespondence: Penglong Wang; Haimin Lei Email wpl581@126.com; hm_lei@126.comBackground: The clinical utility of camptothecin (CPT) is restricted by poor aqueous solubility, high lipophilicity, active lactone ring instability, and off-targeted toxicities. We report here a prostate-specific membrane antigen (PSMA) and esterase dual responsive self-assembled nanoparticles (CPT-WT-H NPs) for highly efficient CPT delivery and effective cancer therapy.Methods and Results: In this study, smart self-assembled nanoparticles CPT-WT-H NPs were elaborately designed and synthesized by combing hydrophobic CPT with hydrophilic PSMA-responsive penta-peptide via a cleavable ester bond. This dual responsive nanoparticle with negatively charged surface first respond to the extracellular PSMA and then to the intracellular esterase, achieving a programmable release of CPT at the tumor site and producing the byproducts of biocompatible glutamic acid and aspartic acid. Our data demonstrated that CPT-WT-H NPs exhibited greatly improved water solubility and stability. Results from MTT and flow cytometry showed CPT-WT-H NPs exhibited significantly higher cytotoxicity as well as apoptosis-inducing activity against PSMA-expressing LNCaP-FGC cells than the non-PSMA-expressing cancer cells, showing excellent cytotoxic selectivity. Moreover, the unique nanostructure provided the efficient transportation of CPT to tumor site, which resulted in the effective inhibition of tumor growth and low systemic toxicity in vivo.Conclusion: CPT-WT-H NPs exhibited excellent in vitro PSMA-response ability and in vivo antitumor activity and safety, holding the promise to become a new and potent anticancer drug. The current research presents a promising strategy for efficient drug delivery.Keywords: CPT prodrug, dual responsive, sequential drug release, prostate-specific membrane antigen, self-assembly

Jianming Wu,&ast; Fangyan Zhou,&ast; Yu Gao Department of Dermatological, Yuying Children’s Hospital, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Gao Email 570875734@qq.comPurpose: Assessment of the clinical effectiveness and safety of 755-nm long-pulse alexandrite laser combined with 0.5% timolol maleate eye drops in treating thicker infantile hemangioma (IH).Materials and Methods: Retrospective analysis of IH treated with 755-nm long-pulse alexandrite laser and topical timolol in the Second Affiliated Hospital of Wenzhou Medical University from October 2019 to October 2020. Seventy-eight cases were included, with a five-week laser treatment interval. Treatment status was documented during the 35 weeks before each treatment, the effect was assessed at the visual analog scale (VAS), and side effects were recorded. During the 6-month follow-up period, the recurrence and residual skin lesions were monitored. The relationship between IH thickness, treatment duration and VAS was analyzed.Results: Among the 78 children with hemangioma, 4 children were treated with a combination of propranolol, fractional laser and cinnamyl alcohol injection due to poor curative effect. Finally, the lesions were effectively alleviated. At the 5th, 15th, 25th, and 35th weeks of treatment, the average VAS of 74 children were 3.56 ± 1.20, 4.61 ± 1.43, 5.63 ± 1.60, and 6.63 ± 1.72, respectively. We analyzed VAS in different thickness groups with Repeated Measures Analysis of Variance(RMANOVA). The results show that the VAS of the thickness 2– 3 mm and 3– 5mm groups were higher than the 5– 7mm and 7– 8mm groups (F group = 440.54, P < 0.05, F time = 448.31, P < 0.05). During the 6-month follow-up period, none of the 74 children relapsed and the residual skin lesions gradually vanished.Conclusion: Combined treatment of IHs with a 755-nm long-pulse alexandrite laser and 0.5% timolol maleate eye drops which has apparent clinical efficacy and safety reduce residual skin lesions and decrease the IH recurrence rate.Keywords: infantile hemangioma, 755-nm long-pulse alexandrite laser, timolol maleate eye drops, thick

Lijin Lin,1– 4,&ast; Ze Chen,4,5,&ast; Ting Ding,1,2,&ast; Hui Liu,4,6,&ast; Feng Zhou,4,7 Xuewei Huang,3,4 Xingyuan Zhang,4,8 Weifang Liu,4,8 Bing-Hong Zhang,9 Yufeng Yuan,10 Peng Zhang,4,8 Xiao-Jing Zhang,4,8 Zhi-Gang She,3,4 Jingjing Cai,4,11 Wenping Chen,1,2 Hongliang Li2– 4,7 1Department of Endocrinology, Huanggang Central Hospital, Huanggang, People’s Republic of China; 2Huanggang Institute of Translational Medicine, Huanggang, People’s Republic of China; 3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Institute of Model Animal of Wuhan University, Wuhan, People’s Republic of China; 5Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 6Neonatology of Gastroenterology, Tongren Hospital of Wuhan University & Wuhan Third Hospital, Wuhan, People’s Republic of China; 7Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 8Basic Medical School of Wuhan University, Wuhan, People’s Republic of China; 9Neonatology Department, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 10Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 11Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongliang Li; Wenping Chen Email lihl@whu.edu.cn; chenwenping@hgyy.org.cnPurpose: To analyze the impact of hyperglycemia on the clinical outcome of COVID-19 in patients with newly diagnosed diabetes (NDD).Patients and Methods: We performed a retrospective study of 3114 cases of COVID-19 without pre-existing diabetes, 351 of which had NDD, in Hubei Province, China. The Cox regression model was used to calculate the risk of adverse clinical outcomes comparing the NDD vs non-NDD group before and after propensity score-matched (PSM) analysis. Patients with NDD were further divided into a sustained hyperglycemia group, a fluctuating group, and a remitted group based on their blood glucose levels during hospitalization as well as into hypoglycemic agent users and nonusers.Results: Compared to the non-NDD individuals, individuals with NDD had a significantly increased risk of all-cause mortality (adjusted HR after PSM, 2.65; 95% CI, 1.49– 4.72; P = 0.001) and secondary outcomes involving organ damage during the 28-day follow-up period. Subgroup analyses indicated that among individuals with NDD, the individuals with remitted hyperglycemia had the lowest 28-day mortality, whereas those with sustained hyperglycemia had the highest (IRR 24.27; 95% CI, 3.21– 183.36; P < 0.001). Moreover, individuals treated with hypoglycemic agents had significantly lower all-cause mortality than those not treated with hypoglycemic agents (IRR 0.08; 95% CI, 0.01– 0.56; P < 0.001).Conclusion: Our study reinforces the clinical message that NDD is strongly associated with poor outcomes in COVID-19 patients. Furthermore, resolved hyperglycemia in the later phase of the disease and the use of hypoglycemic agents were associated with improved prognosis in patients with NDD.Keywords: COVID-19, newly diagnosed diabetes, hyperglycemia, prognosis, blood glucose

Qin Liu,1,&ast; Xin Zhou,1,&ast; Xiaofei Zhang,1 Amanda Louise Strickland,2 wenxin zheng,3 Hao Chen,3 Feng Zhou1 1Department of Pathology, Zhejiang University School of Medicine Women’s Hospital, Hangzhou, 310006, People’s Republic of China; 2Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, USA; 3Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, USA&ast;These authors contributed equally to this workCorrespondence: Feng ZhouDepartments of Pathology, Zhejiang University School of Medicine Women’s Hospital, Hangzhou, 310006, People’s Republic of ChinaTel +86-0571-89991702Email fungchew@zju.edu.cnHao ChenDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, USATel +1-469-419-1538Email Hao.Chen@UTSouthwestern.eduPurpose: To investigate the prevalence of precancers [high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS)] and cancers [squamous cell carcinoma (SCC) and adenocarcinoma (ADC)] in various high-risk human papillomavirus (hrHPV) genotypes or age groups among women with negative for intraepithelial lesion or malignancy (NILM) and hrHPV-positive pap results.Materials and Methods: In total, 26,228 women with NILM/hrHPV+ were included in the study. Among them, 5893 had immediate follow-up biopsy results available and were selected for further prevalence analysis.Results: About 7.6% and 0.7% women with NILM/hrHPV+ had HSIL and AIS, respectively. The prevalence of HSIL+ squamous lesions is significantly higher in HPV-16+ group than that in other genotype groups (p < 0.0001). The prevalence of AIS+ glandular lesions is significantly higher in HPV-18/45+ groups than women in other genotype groups (p < 0.0001). In addition, the prevalence of HSIL+ lesions was significantly higher in age 25– 39 years group than that in age 40– 65 years group and > 65 years group (p < 0.0001). Overall, the prevalence of HSIL+ in younger women was significantly higher than that in older women when using a cutoff age of 40 years (9.3% vs 5.9%, p < 0.0001) or 50 years (8.6% vs 4.9%, p < 0.0001). No significant difference in AIS+ prevalence was found among different age groups (p = 0.611). Interestingly, the prevalence of SCC and ADC in older women (≥ 40 years, 0.3% and 0.3%, respectively) was significantly higher than that in younger women (< 40 years, 0% and 0.07%) (p = 0.001 for SCC; p = 0.02 for ADC).Conclusion: The significant risk of cervical precancers and cancers still exists in women with NILM/hrHPV+, notably the older patient group had a lower risk of cervical precancer, but higher risk of cancer. Therefore, HPV genotyping can be an effective supplemental tool to cytology, and patient age also needs to be considered in the clinical management of patient.Keywords: risk stratification, E6/E7 mRNA genotyping, NILM, hrHPV

Liqin Chen,1,&ast; Jiankun Chen,1,2,&ast; Yuwan Wu,1 Jinyao Zhong,1 Fuzhen Zhou,1 Yuntao Liu,1,2 Aiting Xu,3 Jiqiang Li,1,2 Huayang Cai1 1The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, People’s Republic of China; 2Guangzhou Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Emerging Infectious Diseases, Guangzhou, 510006, Guangdong, People’s Republic of China; 3The People’s Hospital of Yangjiang, Yangjiang, 529500, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiqiang Li; Huayang Cai Email lijiqiangjizhen@163.com ; caihuayang@gzucm.edu.cnBackground: Hypertension has been reported as the most prevalent comorbidity in patients with coronavirus disease 2019 (COVID-19). This retrospective study aims to compare the clinical characteristics and outcomes in COVID-19 patients with or without hypertension.Methods: A total of 944 hospitalized patients with laboratory-confirmed COVID-19 were included from January to March 2020. Information from the medical record, including clinical features, radiographic and laboratory results, complications, treatments, and clinical outcomes, were extracted for the analysis.Results: A total of 311 (32.94%) patients had comorbidity with hypertension. In COVID-19 patients with hypertension, the coexistence of type 2 diabetes (56.06% vs 43.94%), coronary heart disease (65.71% vs 34.29%), poststroke syndrome (68.75% vs 31.25%) and chronic kidney diseases (77.78% vs 22.22%) was significantly higher, while the coexistence of hepatitis B infection (13.04% vs 86.96%) was significantly lower than in COVID-19 patients without hypertension. Computed tomography (CT) chest scans show that COVID-19 patients with hypertension have higher rates of pleural effusion than those without hypertension (56.60% vs 43.40%). In addition, the levels of blood glucose [5.80 (IQR, 5.05– 7.50) vs 5.39 (IQR, 4.81– 6.60)], erythrocyte sedimentation rate (ESR) [28 (IQR, 17.1– 55.6) vs 21.8 (IQR, 11.5– 44.1), P=0.008], C-reactive protein (CRP) [17.92 (IQR, 3.11– 46.6) vs 3.15 (IQR, 3.11– 23.4), P=0.013] and serum amyloid A (SAA) [99.28 (IQR, 8.85– 300) vs 15.97 (IQR, 5.97– 236.1), P=0.005] in COVID-19 patients with hypertension were significantly higher than in patients without hypertension.Conclusion: It is common for patients with COVID-19 to have the coexistence of hypertension, type 2 diabetes, coronary heart disease and so on, which may exacerbate the severity of COVID-19. Therefore, optimal management of hypertension and other comorbidities is essential for better clinical outcomes.Keywords: COVID-19, coronavirus disease, hypertension, clinical characteristics, comorbidities

Fengqi Liu,1,2,&ast; Li Zhong,1,2,&ast; Feifei Zhou,3,&ast; Cheng Zheng,1,4 Kai Zhang,1 Jiachang Cai,5 Hongwei Zhou,5 Kankai Tang,2 Zhaohui Dong,2 Wei Cui,1 Gensheng Zhang1 1Department of Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of China; 2Department of Critical Care Medicine, First Affiliated Hospital, Huzhou Teachers College, The First People’s Hospital of Huzhou, Huzhou, 313000, Zhejiang, People’s Republic of China; 3Department of Critical Care Medicine, Ningbo Medical Center, Li Huili Hospital, Ningbo, Zhejiang, 315040, People’s Republic of China; 4Department of Critical Care Medicine, Taizhou Municipal Hospital, Taizhou, Zhejiang, 318000, People’s Republic of China; 5Department of Clinical Microbiology Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gensheng Zhang; Wei CuiDepartment of Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, cc88 Jiefang Road, Hangzhou, 310009, People’s Republic of ChinaTel +86-571-8778-3636; +86-571-8778-3551Fax +86-571- 87022776Email genshengzhang@zju.edu.cn; zricu@zju.edu.cnPurpose: Candida albicans (C. albicans) candidemia has been well reported in previous studies, while research on non-albicans Candida (NAC) bloodstream infections remains poorly explored. Therefore, the present study aimed to investigate the clinical characteristics and outcomes of patients with NAC candidemia.Patients and Methods: We recruited inpatients with candidemia from January 2013 to June 2020 in a tertiary hospital for this retrospective observational study.Results: A total of 301 patients with candidemia were recruited in the current study, including 161 (53.5%) patients with NAC candidemia. The main pathogens in NAC candidemia were Candida tropicalis (C. tropicalis) (23.9%), Candida parapsilosis (15.6%) and Candida glabrata (10.3%). Patients with NAC candidemia had more medical admissions (P=0.034), a higher percentage of hematological malignancies (P=0.007), a higher frequency of antifungal exposure (P=0.012), and more indwelling peripherally inserted central catheters (P=0.002) than those with C. albicans candidemia. In a multivariable analysis, prior antifungal exposure was independently related to NAC candidemia (adjusted odds ratio [aOR], 0.312; 95% confidence interval [CI], 0.113– 0.859). Additionally, NAC was obviously resistant to azoles, especially C. tropicalis had a high cross-resistance to azoles. However, no significant differences were noted in the mortality rates at 14 days, 28 days and 60 days between these two groups.Conclusion: NAC is dominant in candidemia, and prior antifungal exposure is an independent risk factor. Of note, although the outcomes of NAC and C. albicans candidemia are similar, drug resistance to specific azoles as well as cross-resistance frequently occurs in patients with NAC candidemia, and this drug resistance deserves attention in clinical practice and further in-depth investigation.Keywords: non-albicans candidemia, clinical features, risk factor, cross-resistance

Xiangli Xu,1 Fubo Zhou,2 Yang Hua,2 Beibei Liu,2 Lili Wang,2 Weihong Hou,2 Mingyu Xia2 1Department of Ultrasound, The Second Hospital of Harbin, Harbin, People’s Republic of China; 2Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yang HuaDepartment of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Road, Beijing, 100053, People’s Republic of ChinaTel +86-10-83198923Fax +86-10-83198967Email dryanghua99@163.comObjective: To explore whether current smoking could influence plaque characteristics and determine its correlation to the irregular surface and calcification of carotid plaque.Methods: Three hundred and seventeen patients with severe carotid atherosclerosis stenosis (SCAS) detected by color duplex flow imaging (CDFI) and confirmed by CT angiography (CTA) were recruited. The results of laboratory parameters were collected by using electronic database of the hospital. Computerized tomography (CT) scanning and high-resolution ultrasonography were performed for assessment of plaque morphology, respectively.Results: All enrolled smokers and non-smokers had no significant difference among all characteristics not related to smoking. CT scanning could efficiently identify the difference among enrolled smokers and non-smokers not only for the characteristics related to smoking but also the onsets of carotid plaque. Surface morphology was also efficiently detected by ultrasonography. Further ridge trace analysis showed that ultrasonography is efficient for diagnosis of calcified plaque compared with gold standard for plaque diagnosis. Further correlation analysis showed that ultrasonography parameters could offer reliable evidence for plaque scores, which was associated with age index. Ultrasonography parameters could efficiently differentiate plaque morphologies among enrolled smokers and never-smokers.Conclusion: Current smoking was positively associated with plaque calcification onsets, and smoking cessation could efficiently attenuate such injury. High-frequency ultrasound can clearly distinguish the details of calcification with promising clinical significance for current smoking patients.Keywords: smoking, ultrasonography, carotid plaque, calcification

Xiangli Xu,1 Yang Hua,2 Beibei Liu,2 Fubo Zhou,2 Lili Wang,2 Weihong Hou2 1Department of Ultrasound, the Second Hospital of Harbin, Harbin, People’s Republic of China; 2Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yang HuaDepartment of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Road, Beijing, 100053, People’s Republic of ChinaTel +86-10-83198923Fax +86-10-83198967Email dryanghua99@163.comPurpose: To investigate the relationship between calcification characteristics of carotid atherosclerotic plaque and lipid rich necrotic core (LRNC) and intraplaque hemorrhage (IPH).Methods: Patients with severe carotid stenosis undergoing carotid endarterectomy (CEA) were selected. Ultrasound and CT angiography (CTA) were performed to evaluate the calcification characteristics of the plaque before the surgery.Results: A total of 142 patients were included and 142 pathological specimens of postoperative plaque were obtained accordingly. There were 78 plaques (54.9%) with LRNC and 41 (28.9%) with IPH. The plaque with LRNC had higher calcification rate (93.6%) compared with the plaque with IPH (87.8%). LRNC was often found in multiple calcification (P = 0.003) and mixed type calcification (P = 0.001). Multiple calcification was more likely to combine with IPH (P = 0.008), while simple basal calcification was not likely to combine IPH (P = 0.002). Smaller granular calcification was more likely to be associated with IPH (P < 0.05). In multivariate regression analysis of IPH and calcification characteristics, simple basal calcification was still a protective factor for IPH (OR, 0.25; 95% CI, 0.09– 0.66; P = 0.005), while multiple calcification was closely related to the occurrence of IPH (OR, 3.58; 95% CI, 1.49– 8.61; P = 0.004).Conclusion: Calcification characteristics of carotid atherosclerotic plaques are closely related to the vulnerability of plaques, especially multiple calcification and mixed type calcification.Keywords: carotid artery, atherosclerotic plaque, intraplaque calcification, vulnerable plaque

Fujun Zhou,1,* Cheng Cao,2,* Huiping Chai,2 Jingfang Hong,3 Min Zhu1 1Department of Health and Nursing, Anhui Vocational College of City Management, Hefei City, Anhui Province, People’s Republic of China; 2Department of Thoracic Surgery, 4th Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China; 3School of Nursing, Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng CaoDepartment of Thoracic Surgery, 4th Affiliated Hospital of Anhui Medical University, No. 100 Huaihai Avenue, Hefei, 230022, Anhui Province, People’s Republic of ChinaTel/Fax +86 0551-66331040 Email caochengaysfy@163.comBackground: Smoking is the most common cause of chronic obstructive pulmonary disease (COPD), and the early diagnosis for COPD remains poor. Exploring the molecular mechanism and finding feasible biomarkers will be beneficial for clinical management of COPD. Circular RNAs (circRNAs) are noncoding RNAs that act as miRNA sponges to regulate the expression levels of genes, leading to the changes of cellular phenotypes and disease progression. CircRNA HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (circ-HACE1) was abnormally expressed after the induction of cigarette smoke extract (CSE) in cell model. This study was performed to explore its function and mechanism in COPD.Methods: Circ-HACE1, microRNA-485-3p (miR-485-3p) and toll-like receptor 4 (TLR4) detection was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis/cell cycle were respectively examined using cell counting kit-8 (CCK-8) and flow cytometry. Inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Oxidative stress was evaluated through the measurement of malondialdehyde (MDA) and superoxide dismutase (SOD). The target binding analysis was conducted via dual-luciferase reporter assay. Western blot was employed for protein expression detection of TLR4.Results: Circ-HACE1 was overexpressed in smokers or smokers with COPD and CSE upregulated circ-HACE1 expression in 16HBE cells. Knockdown of circ-HACE1 attenuated CSE-stimulated cell viability and cell cycle repression, as well as the enhancement of cell apoptosis, inflammatory response and oxidative stress. MiR-485-3p was a target of circ-HACE1. Circ-HACE1 regulated CSE-induced cell injury via targeting miR-485-3p. TLR4 was a downstream target of miR-485-3p, and miR-485-3p inhibited the CSE-induced cell damages by directly downregulating the level of TLR4. Circ-HACE1/miR-485-3p regulated TLR4 expression in CSE-treated 16HBE cells, and TLR4 overexpression also reversed all effects of si-circ-HACE1 on CSE-treated 16HBE cells.Conclusion: These findings elucidated that circ-HACE1 contributed to the CSE-induced cell damages in COPD cell models via regulating TLR4 by acting as the sponge of miR-485-3p.Keywords: circ-HACE1, chronic obstructive pulmonary disease, cigarette smoke extract, miR-485-3p, TLR4

Fangwei Zhou, Caiming Xu, Yanxiang Sun, Xuehui Meng Humanities and Management School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xuehui MengHumanities and Management School of Zhejiang Chinese Medical University, 548# Binwen Road, Binjiang District, Hangzhou, 310051, People’s Republic of ChinaTel/Fax +86 571-86633056Email mengxuehui@aliyun.comPurpose: This study aimed to analyze the status of patient satisfaction in outpatients of tertiary hospitals and the factors affecting patient satisfaction, in order to provide a scientific basis for improving patient satisfaction.Methods: A total of 6480 surveys of outpatients were conducted by a cross-sectional study in 16 tertiary hospitals in the Zhejiang province of China. The main contents of the survey were the basic characteristics of patients. Statistical description, single-factor analysis and binary logistic regression analysis were used to screen influencing factors.Results: Results of this study showed that the total satisfaction score of outpatients was 87.13± 13.47, and higher scored factors in the survey factors were nursing level, the convenience of registration and convenience of appointment diagnosis and treatment. The factors with lower scores were treatment effect, environmental sanitation and comfort and other staffs’ attitudes. Hospital managers should pay attention to the improvement of treatment level, environmental sanitation and comfort and other staffs’ attitudes.Conclusion: In the process of serving outpatients, doctors should pay more attention to patients who are male, 31– 45 years old or over 60 years old, permanent residents, from public institutions, possessed postgraduate education, without medical insurance, and who visiting paediatrics and Chinese medicine hospitals.Keywords: outpatient satisfaction, tertiary hospitals, patient, influencing factor

Yu Tan,1,&ast; Feng Zhou,2,&ast; Dejiang Yang,1 Xiaowei Zhang,1 Meihong Zeng,1 Lei Wan1 1Department of Neurology, The Third Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330008, People’s Republic of China; 2Department of Neurology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai City, Guangdong Province, 519000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu TanDepartment of Neurology, The Third Affiliated Hospital of Nanchang University, No. 128 Xiangshan Road, Nanchang City, Jiangxi Province, 330008, People’s Republic of ChinaEmail YuTanhospital@163.comBackground: Ischemic stroke is a destructive cerebrovascular disorder related to oxidative stress; NOX2 is a major source for ROS production; and miR-126a-5p is involved in several diseases, such as abdominal aortic aneurysm. We investigated the role of miR-126a-5p in regulating NOX2 in ischemic stroke.Methods: MiR-126a-5p and NOX2 were examined in the brains of rats subjected to cerebral ischemia/reperfusion (I/R) by RT-PCR and Western blot. MiR-126a-5p agomir was delivered to examine the effects of miR-126a-5p on I/R injury. The neurological deficit, infarct volume, and brain water content were evaluated. NOX activity, ROS production, and MDA and SOD levels were detected to assess oxidative stress. H&E staining was used to examine cell state. Apoptosis was evaluated by TUNEL, caspase-3 activity, and cleaved-caspase-3 protein level. The relationship between miR-126a-5p and NOX2 was analyzed by bioinformatics and luciferase reporter assay. MiR-126a-5p mimic, miR-126a-5p inhibitor, or pcDNA-NOX2 were transfected in SH-SY5Y cells to further assess the effects of miR-126a-5p on OGD/R-induced cells injury.Results: NOX2 was upregulated and miR-126a-5p was down-regulated in the brains of I/R rats. MiR-126a-5p agomir obviously reduced the neurological deficit, infarct volume, brain water content, oxidative stress, and apoptosis in I/R rats. MiR-126a-5p targeted NOX2 directly and regulated NOX2 negatively. Moreover, miR-126a-5p mimic elevated cell viability and inhibited oxidative stress and apoptosis in OGD/R-treated SH-SY5Y cells, while miR-126a-5p inhibitor had the opposite effects. NOX2 overexpression antagonized the protective effects of miR-126a-5p mimic on OGD/R-induced cell injury.Conclusion: MiR-126a-5p is a novel potential target for ischemic stroke therapy due to its protection against cerebral I/R injury via directly targeting NOX2.Keywords: oxidative stress, NOX2, miR-126a-5p, cerebral ischemia/reperfusion

Youshi Meng,1,2,* Chunli Zhang,1,2,* Lucong Liang,1,2,* Lei Wei,1,2 Hao Wang,1,2 Fengkun Zhou,1,2 Rongjie Li,1,2 Donghua Zou,1,2 Xiaohua Huang,3 Jie Liu4 1Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 2Department of Neurology, The First People’s Hospital of Nanning, Nanning, Guangxi, 530022, People’s Republic of China; 3Department of Neurology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China; 4Department of Cardiology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohua HuangDepartment of Neurology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of ChinaEmail newxiaohua66@163.comJie LiuDepartment of Cardiology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of ChinaTel +867712636189Email gxnnliujie@163.comPurpose: Carotid atherosclerosis is a kind of systemic atherosclerosis in the carotid arteries. However, the efficiency of treatment is insufficient. Therefore, it is urgent to find therapeutic targets and deepen the understanding of carotid atherosclerosis.Materials and Methods: In this study, we analyzed differentially expressed genes (DEGs) between atheroma plaque and macroscopically intact tissue (control samples). Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analysis based on the DEGs. Four methods were used to identify the hub genes in the protein–protein interaction networks of the DEGs. Furthermore, we also performed network module analysis to reveal carotid atherosclerosis-related gene modules and biological functions.Results: The enrichment results showed that the biological functions were related to inflammation, immunity, chemokine and cell adhesion molecule, such as PIK-Akt signaling pathway, Rap1 signaling pathway, MAPK signaling pathway, NOD-like receptor signaling pathway and B cell receptor signaling pathway. In addition, we screened the hub genes. A total of 16 up-regulated genes (C3AR1, CCR1, CCR2, CD33, CD53, CXCL10, CXCL8, CXCR4, CYBB, FCER1G, FPR2, ITGAL, ITGAM, ITGAX, ITGB2, and LILRB2) were identified as hub genes. A total of 5 gene modules were obtained. We found that biological functions obtained for each cluster were mostly related to immunity, chemokines and cell adhesion molecules.Conclusion: The present study identified key DEGs in atheroma plaque compared with control samples. The key genes involved in the development of carotid atherosclerosis may provide valuable therapeutic targets for carotid atherosclerosis.Keywords: identification of key genes, carotid atherosclerosis, cluster analysis

Fengkun Zhou,1,2,* Deyao Chen,1,2,* Guoying Chen,1,2,* Peiling Liao,1,2 Rongjie Li,1,2 Qingfang Nong,1,2 Youshi Meng,1,2 Donghua Zou,1 Xianfeng Li1,2 1Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 2Department of Neurology, The First People’s Hospital of Nanning, Nanning, Guangxi, 530022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Donghua Zou; Xianfeng LiThe Fifth Affiliated Hospital of Guangxi Medical University, 89 Qixing Road, Nanning, Guangxi, 530022, People’s Republic of ChinaTel +867712636189Email danvor0922@hotmail.com; lxianf@sina.comPurpose: Alzheimer’s disease (AD) and vascular dementia shared similar symptoms, the aim of the present study was to identify potential differences in the mechanisms underlying the two diseases.Materials and Methods: The data set including AD, vascular dementia, and control samples was carried out gene differential expression analysis, weighted gene co-expression network analysis, functional enrichment, protein–protein interaction network construction, and least absolute shrinkage and selection operator analysis to reveal the differences in the mechanisms underlying the two diseases and potential diagnostic gene signature.Results: We identified the gene modules related to AD or vascular dementia. Enrichment analysis of module genes and construction of a protein–protein interaction network suggested that the “brown” module may be involved in a chemokine pathway, the “blue” module may be involved in cortisol synthesis and secretion, and the “turquoise” module may be involved in cholinergic synapse transmission. The hub gene-based signature index may be a biomarker of AD and vascular dementia and may even differentiate the two diseases from each other with high area under curve.Conclusion: Our results identified not only core pathways involved in both AD and vascular disease, but also their potentially specific pathways. We proposed the hub gene-based signature index may be useful for diagnosing AD and vascular dementia.Keywords: Alzheimer’s disease, vascular dementia, weighted gene co-expression network analysis, LASSO, WGCNA

Menglei Zhang,1,2,* Fangyue Zhou,1,* Yuan He,3 Xiang Tao,4 Keqin Hua,1,2 Jingxin Ding1,2 1Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China; 2Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, People’s Republic of China; 3Public Health School of Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingxin DingDepartment of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, 128 Shen-Yang Road, Shanghai, 200011, People’s Republic of ChinaTel +86-13918206746Fax +86-21-63455090Email djxdd@sina.comPurpose: This study aimed to establish a predictive model for lymph node involvement (LNI) in patients with borderline ovarian tumor (BOT) using clinicopathological factors.Patients and Methods: We collected clinical data from consecutive patients who underwent lymphadenectomy for BOT between 2001 and 2018 and analyzed their clinicopathological features. Multivariate logistic regression was used to identify all independent risk factors associated with LNI; these were then incorporated into the prediction model.Results: In total, we included 248 patients with BOT who were undergoing lymphadenectomy. These were divided into a training cohort (n=174) and a validation cohort (n=74). When considering histopathological data, 16 and 5 patients were identified to have LNI in the training and validation cohorts, respectively. Overall, 13.5% (21/156) patients with serous BOT had LNI while 0% (0/92) patients with non-serous BOT had LNI. We identified several predictors of LNI: the largest tumor being ≥ 12.2cm in diameter, the presence of lesions on the ovarian surface, and the presence of pelvic or abdominal lesions. We created a prediction model and nomogram that incorporated these three risk factors for serous BOT. The model achieved good discriminatory abilities of 0.951 and 0.848 when predicting LNI in the training and validation cohorts, respectively. The LNI-predicting nomogram had an area under curve (AUC) of 0.951 and generated well-fitted calibration curves.Conclusion: Non-serous BOT may not require lymphadenectomy as part of surgical staging. The individual risk of LNI in patients with serous BOT can be accurately estimated using our prediction model and nomogram. The use of LNI criteria provides a practical way to support the clinician in making an optimal decision relating to surgical scope for patients with BOT.Keywords: lymph node involvement, borderline ovarian tumor, lymphadenectomy, prediction model, nomogram

Qinglin Li,1,* Yan Wang,2,* Zhi Mao,1 Hongjun Kang,1 Feihu Zhou1,3 1Department of Critical Care Medicine, The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Health Care, The Second Medical Centre, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Chinese PLA General Hospital National Clinical Research Center for Geriatric Diseases, Beijing, 100853, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feihu ZhouDepartment of Critical Care Medicine, The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of ChinaTel + 86-10-66938148Fax + 86-10-88219862Email feihuzhou301@126.comPurpose: We examined the relationship between different levels of serum sodium and mortality among elderly patients with acute kidney injury (AKI).Methods: We retrospectively enrolled elderly patients from Chinese PLA General Hospital from 2007, to 2018. All-cause mortality was examined according to eight predefined sodium levels: < 130.0 mmol/L, 130.0– 134.9 mmol/L, 135.0– 137.9 mmol/L, 138.0– 141.9 mmol/L, 142.0– 144.9 mmol/L, 145.0– 147.9 mmol/L, 148.0– 151.9 mmol/L, and ≥ 152.0 mmol/L. We estimated the risk of all-cause mortality using a multivariable adjusted Cox analysis, with a normal sodium level of 135.0– 137.9 mmol/L as a reference.Results: In total, 744 patients were suitable for the final evaluation. After 90 days, the mortality rates in the eight strata were 36.1, 27.8, 19.6, 24.4, 30.7, 48.6, 52.8, and 57.7%, respectively. In the multivariable adjusted analysis, patients with sodium levels < 130.0 mmol/L (HR: 2.247; 95% CI: 1.117– 4.521), from 142.0 to 144.9 mmol/L (HR: 1.964; 95% CI: 1.100– 3.508), from 145.0 to 147.9 mmol/L (HR: 2.942; 95% CI: 1.693– 5.114), from 148.0 to 151.9 mmol/L (HR: 3.455; 95% CI: 2.009– 5.944), and ≥ 152.0 mmol/L (HR: 3.587; 95% CI: 2.151– 5.983) had an increased risk of all-cause mortality. After 1 year, the mortality rates in the eight strata were 58.3, 47.8, 33.7, 38.9, 45.5, 64.3, 69.4, and 78.4%, respectively. Patients with sodium levels < 130.0 mmol/L (HR: 1.944; 95% CI: 1.125– 3.360), from 142.0 to 144.9 mmol/L (HR: 1.681; 95% CI: 1.062– 2.660), from 145.0 to 147.9 mmol/L (HR: 2.631; 95% CI: 1.683– 4.112), from 148.0 to 151.9 mmol/L (HR: 2.411; 95% CI: 1.552– 3.744), and ≥ 152.0 mmol/L (HR: 3.037; 95% CI: 2.021– 4.563) had an increased risk of all-cause mortality.Conclusion: Sodium levels outside the interval of 130.0– 141.9 mmol/L were associated with increased risks of 90-day mortality and 1-year mortality in elderly AKI patients.Keywords: serum sodium, acute kidney injury, elderly, mortality

Chenglong Sun,1,2,* Fei Zhou,3,* Xuefei Li,4 Chao Zhao,4 Wei Li,3 Jiayu Li,3 Anwen Xiong,3 Jia Yu,3 Guanghui Gao,3 Qi Wang,3 Fengying Wu,3 Caicun Zhou3 1Radiotherapy Department, Anhui No. 2 Provincial People’s Hospital, Hefei 230041, Anhui, People’s Republic of China; 2Medical College of Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China; 3Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China; 4Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengying Wu; Caicun ZhouDepartment of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai 200433, People’s Republic of ChinaTel +086 13167060870; +086 13301825532Email fywu@163.com; caicunzhoudr@126.comIntroduction: Immune checkpoint inhibitor (ICI) monotherapy has limited efficacy in patients with non-small cell lung cancer (NSCLC) and brain metastases (BMs). With the wide use of ICI-based combinations, the efficacy of different ICI combination strategies in patients with NSCLC and BMs needs to be further elucidated.Methods: We retrospectively reviewed 526 patients with non-small cell lung cancer (NSCLC) treated with ICIs from January 2016 to December 2019 in the Shanghai Pulmonary Hospital. Patients with BMs treated with ICIs were further divided into two groups: those with BM prior to the ICI treatment (pBM group), and those with BM after the treatment (aBM group). We assessed intracranial progression-free survival (IPFS), systemic progression-free survival (SPFS), overall survival (OS), intracranial objective response rate (IORR), and intracranial disease control rate (IDCR).Results: We found 77 patients out of 526 with BMs; 69 presented the BMs prior to the ICI treatments and 8 showed BMs after the ICI treatments. In the pBM group, the median IPFS and SPFS were 7.39 months and 5.39 months, respectively. Combination therapy significantly improved both the IPFS (p=0.007) and the SPFS (p=0.007) when compared with monotherapy. Further analysis demonstrated that ICIs combined with chemotherapy significantly improved both the IPFS (p=0.009) and the SPFS (p=0.006) when compared with monotherapy. While ICIs combined with anti-angiogenic therapy improved the SPFS (p=0.005) but not the IPFS (p=0.139). The median OS was 27.43 months for patients in the pBM group. Further analyses suggested that combination treatment also improved the OS when compared with monotherapy (p=0.003). Subgroup analysis results showed that ICIs combined with chemotherapy led to better OS than ICIs monotherapy (p=0.006). Radiotherapy had no significant impact on survival (IPFS p=0.272, OS p=0.142) in the patients of the pBM group.Conclusion: ICIs combined with chemotherapy demonstrated survival benefits over ICI monotherapy in patients with NSCLCs and BMs.Keywords: NSCLC, immune checkpoint inhibitors, brain metastases, survival, chemotherapy, anti-angiogenesis

Qinglin Li, 1,* Tianyi Zhang, 2,* Fei Li, 3, 4,* Zhi Mao, 1 Hongjun Kang, 1 Ling Tao, 3,* Feihu Zhou, 1, 3,* Yue Cai 1, 3, 4,* 1Department of Critical Care Medicine, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 2Institution of Hospital Management, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 3Department of Cardiology, Xijing Hospital, Xi’an 710032, People’s Republic of China; 4Department of Infectious Diseases, Huo Shen Shan Hospital, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feihu Zhou Tel +86 10 6693 8148Email feihuzhou301@126.comYue Cai Tel + 86 159 0238 8078Email caiyueclear1981@163.comObjective: Severe or critical patients with coronavirus disease 2019 (COVID-19) are at increased risk for developing acute kidney injury (AKI). However, the rate of AKI in patients of different severities and independent predictive factors associated with AKI are not well understood.Patients and Methods: We enrolled 107 severely or critically ill elderly patients with COVID-19 who were admitted to the intensive care unit (ICU) in Wuhan, China. AKI was defined according to the 2012 KDIGO criteria. We explored the association between AKI and in-hospital mortality using logistic regression. A predictive nomogram was formulated to predict the AKI development of patients with COVID-19 based on multivariate logistic regression.Results: A total of 107 elderly patients were enrolled during the study period. The mean age was 70 (64– 78) years, and 69 (64.5%) were men. For the 107 patients, the degree of severity of COVID-19 was categorized as 37 patients with the severe type (34.6%) and 70 patients with the critical type (65.4%). Overall, 48 of the 107 patients (44.9%) developed AKI during their hospitalization, while AKI occurred in 7 (18.9%) out of the 37 severe patients and 41 (44.9%) out of the 70 critical patients. Of the AKI patients, 35.4% (17/48) required continuous renal replacement therapy, including 14.3% of AKI patients in severe cases and 39.0% of AKI patients in critical cases. Kaplan–Meier analysis demonstrated that patients with AKI had a significantly higher risk for in-hospital mortality than severely and critically ill patients without AKI. Multivariate logistic regression analysis showed that AKI (OR = 33.74; 95% CI = 3.34– 341.29; P = 0.003), septic shock (OR = 15.58; 95% CI = 2.08– 116.78; P = 0.008), invasive mechanical ventilation (OR = 18.44; 95% CI = 2.35– 144.69; P = 0.006), and oxygenation index (OR = 0.99; 95% CI = 0.98– 1.000; P = 0.014) were independent risk factors for in-hospital mortality. A nomogram was established based on the multivariate analysis results. The C-index for the developed AKI model was 0.935 (95% CI, 0.892– 0.978); when 10-fold cross validation was used to validate the model, the corrected C-index was 0.825.Conclusion: AKI is common among COVID-19 patients admitted to the ICU and is recognized as a marker of disease severity. The proposed nomogram accurately predicted AKI development in ICU patients with COVID-19 based on individual characteristics. Therefore, the strategy for kidney protection against severe or critical pneumonia is appropriate.Keywords: coronavirus disease 2019, acute kidney injury, diagnosis, nomogram, in-hospital mortality