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Yidan Xu,1,&ast; Lu Zhang,1,&ast; Zhiyang Chen,1 Xiaonan Sun,1 Mengdan Zhao,1 Qirui Wu,2 Jiqing Hao1 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiqing Hao, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, 81 Meishan Road, Hefei, Anhui, People’s Republic of China, Tel +86-13965029739, Email haojiqing@ahmu.edu.cnPurpose: This study aims to explore the association of inflammatory markers such as the Systemic Immune-Inflammatory Index (SII) and LANR with the comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and lung cancer.Patients and Methods: A cross-sectional analysis was conducted on the clinical data of 309 patients with COPD only and 193 patients with COPD and lung cancer who attended the First Affiliated Hospital of Anhui Medical University. Additionally, we examined autonomous risk factors that contribute to the simultaneous development of COPD and lung cancer through univariate and multivariate logistic regression analyses. This analysis resulted in the development of a nomogram model for visual representation. The effectiveness of the model was assessed using a receiver operating characteristic (ROC) curve, calibration curve, and clinical decision analysis (DCA) curve, with internal validation conducted via repeated sampling methods.Results: Multivariate analysis of clinical characteristics and inflammatory markers showed that smoking history of > 60 pack-years, hemoptysis, emphysema, WBC count > 5.53 (× 10^9/L), SII > 629.285, and LANR < 11.39 were significantly associated with the comorbidity of COPD and lung cancer. These factors were subsequently integrated into the nomogram model. The AUC of the model stood at 0.849 (95% CI: 0.815– 0.882), demonstrating a notable improvement over the COPD-LUCSS scoring system (AUC: 0.716, 95% CI: 0.671– 0.761). The DCA curve indicated a notable clinical advantage provided by the model. Additionally, patients with stage IV tumors exhibited elevated SII levels and reduced LANR levels compared to earlier stages, indicating potential prognostic significance for both markers.Conclusion: Increased levels of the inflammatory markers SII and LANR are associated with the risk of comorbidity of COPD and lung cancer.Keywords: lung cancer, inflammation, systemic immune-inflammation index, nomogram, LANR, chronic obstructive pulmonary disease

Ying Gao,1,2 Jie Hao,1 Zhendong Zhang1 1Department of Breast and Thyroid Surgery, Tianjin Union Medical Center, Tianjin, 300121, People’s Republic of China; 2Department of Thyroid and Neck Cancer, Tianjin Medical University Cancer Hospital, National Cancer Clinical Research Center, Tianjin Cancer Clinical Research Center, Tianjin Key Laboratory of Cancer Prevention and Treatment, Tianjin, 300060, People’s Republic of ChinaCorrespondence: Zhendong Zhang; Jie Hao, No. 190 Jieyuan Road, Hongqiao District, Tianjin, 300121, People’s Republic of China, Tel +8613302182253 ; +8618920392330, Email zhangzhendongdoc@sina.com; haojie1215@126.comAbstract: Decision-making regarding adjuvant chemotherapy for older adults with breast cancer is a challenge because older adult patients often have poor physical health, frailty, and age-related comorbidities, which can compromise treatment outcome. Due to these considerations, doctors tend to use less chemotherapy for breast cancer in older adults. However, older patients in good general health could still benefit from chemotherapy. Careful benefit-risk assessment is essential to provide best care for each older adult patient. Due to a rapidly aging population, breast cancer in older adults is becoming a serious public health issue in China. In this mini review, we discuss the need, means, and tools to assess the benefits and risks of adjuvant chemotherapy in older adults with breast cancer. The contents of this review may drive decision-making with regard to the use and selection of adjuvant chemotherapy for older adult patients in China who are fit for the treatment.Keywords: breast cancer, older adult patients, chemotherapy, assessment

Mengnan Li,1,2,&ast; Xifeng Yang,1,2,&ast; Ru Li,1,2 Baofeng Wu,1,2 Jinxuan Hao,1,2 Yijie Qi,1,2 Tao Bai,1 Luyang Yang,1 Yi Zhang,3 Yunfeng Liu1,4 1Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Clinical Research Center of Endocrine and Metabolic Diseases in Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Email nectarliu@163.com Yi Zhang, Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China, Email yizhang313@163.comPurpose: There is evidence that long-term vascular risk remains increased in patients with hyperthyroidism even after normalization of thyroid function, and the mechanisms that regulate this risk are unclear. The aim of this study was to assess how visceral fat area and subcutaneous fat area change after hyperthyroidism treatment, and to further explore the relationship between thyroid hormones, abdominal fat area (visceral fat area and subcutaneous fat area), and lipids.Patients and Methods: 50 patients with newly diagnosed Graves’ disease were selected. Anthropometric parameters (weight, height, body mass index, waist circumference, neck circumference), laboratory parameters (thyroid hormones, lipid metabolism indices), abdominal fat area (visceral fat area and subcutaneous fat area), and drug dose were collected. Measurements were made at baseline, 6 and 12 months after treatment. We used linear mixed-effects models for analysis.Results: The results showed that the following indexes changed significantly at different time points: visceral fat area, subcutaneous fat area, free triiodothyronine, free thyroxine, thyroid stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, body weight, neck circumference, body mass index, waist circumference, and drug dose (All P< 0.001). We found that free triiodothyronine and free thyroxine were significantly negatively associated with abdominal fat area (P< 0.01). There was no significant correlation between drug dose and abdominal fat area (P> 0.05). Total cholesterol and low-density lipoprotein were significantly positively associated with abdominal fat area (P< 0.01). However, high-density lipoprotein (P=0.06) was not correlated with abdominal fat area. Moreover, the results showed a significant negative correlation between thyroid hormones and lipids (P< 0.001).Conclusion: After anti-thyroid medicine treatment, patients had elevated visceral fat area and subcutaneous fat area and altered lipid profiles. These changes may be one of the reasons why metabolic and cardiovascular diseases remain increased after thyroid function is restored.Keywords: visceral fat area, subcutaneous fat area, thyroid hormones, lipids, Graves’ disease

Dan Li,1,2,&ast; Donglin Zhang,3,&ast; Minjuan Wang,2 Jianfeng Hao,2 Yongquan Shi,4 Dake Chu1,5 1Graduate School, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Scientific Research Management Department, The Third Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China; 3General Medicine Department, The First Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China; 4State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, People’s Republic of China; 5Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dake Chu, Graduate School, Xi’an Jiaotong University, No. 28 Xianning West Road, Xi’an, Shaanxi Province, 710049, People’s Republic of China, Tel/Fax +86-2985323922, Email chudake@xjtu.edu.cnPurpose: We conducted a multicenter cross-sectional study in central and western China to explore the association between inflammatory diet and stomach cancer odds.Patients and Methods: Participants from five hospitals in the central and western regions were collected. All participants completed the questionnaire we provided before the gastroscopy examination, which includes inquiries about risk factors for stomach cancer and food frequency. All participants underwent gastroscopy, and a mucosal biopsy was confirmed pathologically. Pathological findings were classified as chronic gastritis group, precancerous lesions group and stomach cancer group. Dietary Inflammatory Index (DII) scores were calculated based on the frequency of food occurrences in the questionnaire, and finally SPSS was used to calculate the correlation between variables.Results: A total of 1162 patients were included in this study, including 668 cases of chronic gastritis, 411 cases of precancerous lesions, and 83 cases of cancer. A single factor analysis was conducted to examine the risk factors of stomach cancer, revealing a significant association between a pro-inflammatory diet and the stomach cancer odds (p value < 0.05). The results of binary classification analysis further confirmed that a pro-inflammatory diet is a risk factor for stomach cancer 【odds ratio (OR) =7.400)】. Moreover, correlation analysis demonstrated a positive correlation between the severity of gastric mucosal diseases and an inflammatory diet (including anti-inflammatory and pro-inflammatory diets) (rs=0.274, p-value < 0.001).Conclusion: Pro-Inflammatory diet is a risk factor for stomach cancer, and may accelerate the progression of stomach mucosal disease.Keywords: stomach cancer, chronic gastritis, precancerous lesions, dietary inflammatory index, pro-inflammatory diet

Naigeng Wang,1 Fei Li,2 Jing Du,3 Jianhong Hao,1 Xin Wang,2 Yueru Hou,3 Zhenguo Luo1 1Department of Anesthesiology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of ChinaCorrespondence: Zhenguo Luo, Email luozhenguo@stu.xjtu.edu.cnBackground: This study aims to investigate the protective effect of quercetin against global cerebral ischemia‒reperfusion (GCI/R) injury in rats and elucidate the underlying mechanism.Methods: A GCI/R injury rat model was established using a four-vessel occlusion (4-VO) method. An oxygen–glucose deprivation/reoxygenation (OGD/R) injury model was induced in BV2 cells. The extent of injury was assessed by evaluating neurological deficit scores (NDS) and brain water content and conducting behavioral tests. Pathomorphological changes in the prefrontal cortex were examined. Additionally, the study measured the levels of inflammatory cytokines, the degree of microglial activation and polarization, and the protein expression of Toll-like receptor 4 (TLR4) and TIR-domain-containing adaptor inducing interferon-β (TRIF).Results: Quercetin pretreatment significantly ameliorated neurological impairment, improved learning and memory abilities, and reduced anxiety in rats subjected to GCI/R injury. Furthermore, quercetin administration effectively mitigated neuronal injury and brain edema. Notably, it suppressed microglial activation and hindered polarization toward the M1 phenotype. Simultaneously, quercetin downregulated the expression of TLR4 and TRIF proteins and attenuated the release of IL-1β and TNF-α.Conclusion: This study highlights the novel therapeutic potential of quercetin in alleviating GCI/R injury. Quercetin demonstrates its neuroprotective effects by inhibiting neuroinflammation and microglial activation while impeding their transformation into the M1 phenotype through modulation of the TLR4/TRIF pathway.Keywords: quercetin, cerebral ischemia, neuroprotection, neuroinflammation

Jie Hao,1– 3,&ast; Yu Liu,1,&ast; Fengli Guo,1,4 Guiming Fu,1,5 Junya Ning,2,3 Xianhui Ruan,1 Xiangqian Zheng,1 Ming Gao1– 3 1Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Tianjin Union Medical Center of Nankai University, Tianjin, People’s Republic of China; 3Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical Center Nankai University, Tianjin, People’s Republic of China; 4Department of Thyroid and Breast Surgery, Binzhou Medical University Hospital, Binzhou, People’s Republic of China; 5Thyroid-Otolaryngology Department, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangqian Zheng; Ming Gao, Email xzheng05@tmu.edu.cn; headandneck2008@126.comBackground: We planned to explore the underlying mechanism and clinical significance of lnc-SNHG5 and RPS3 in hepatocellular carcinoma in this current study.Methods: The expression of Lnc-SNHG5 and RPS3 in HCC tissues and several cell lines were affirmed, respectively, using UALCAN, TIMER, TCGA and RT-qPCR assay. Cell proliferation ability was detected by colony formation assay and CCK8 assay. Cell apoptosis was monitored by flow cytometry assay. Next, the RPS3 expression levels and the related proteins in NFκB pathway were examined using Western blot analysis. The role of lnc-SNHG5 and RPS3 in vivo was identified by subcutaneous tumor bearing experiment.Results: Lnc-SNHG5 was significantly increased in hepatocellular carcinoma tissues and in hepatocellular carcinoma cells. Further investigation showed that up-regulated lnc-SNHG5 promoted cell viability and cell proliferation ability of SMMC-7721 cells by regulating the cell apoptosis, while down-regulation of lnc-SNHG5 revealed opposite results in QGY-7703 cells. In terms of mechanism, we found that lnc-SNHG5 interacted with RPS3. Lnc-SNHG5 regulated the NFκB pathway through RPS3 in vitro and in vivo.Conclusion: This study suggested that lnc-SNHG5 expression was signally up-regulated in hepatocellular carcinoma, and lnc-SNHG5 promoted the malignant phenotypes in vitro and in vivo via directly regulating RPS3-NFκB pathway. Lnc-SNHG5 might be a target for molecular targeted therapy, a potential and novel diagnostic marker for HCC patients.Keywords: long non-coding RNA, SNHG5, RPS3, HCC, NFκB pathway

Jia Hao,1 Weijian Lu,2 Wanqi Gong,3 Xiaoxi Chen4 1School of English for International Business, Guangdong University of Foreign Studies, Guangzhou, People’s Republic of China; 2School of Business and Economics, Maastricht University, Maastricht, Netherlands; 3School of Journalism and Communication, Guangdong University of Foreign Studies, Guangzhou, People’s Republic of China; 4School of Management, Jinan University, Guangzhou, People’s Republic of ChinaCorrespondence: Wanqi Gong, School of Journalism and Communication, Guangdong University of Foreign Studies, No. 1689 Bai Yun Avenue, Guangzhou, 510420, People’s Republic of China, Tel +86 20 39328095, Email yunkigong@gmail.comPurpose: Inspiration is a psychological construct that has been relatively understudied in times of difficulty. This study aims to investigate the mediating effect of inspiration on the relationship between emotions and coping strategies in the context of adversity and to testify the effect in Chinese as well as the International societies.Participants and Methods: Using the snowball sampling method, two survey studies were conducted among 523 Chinese and 503 international participants during and soon after the local Covid-19 outbreak to testify how positive and negative emotions contributed to various coping strategies and whether the experience of inspiration mediated these relations. Structural equation modeling (SEM) was used to analyze the data.Results: Positive emotions had a higher impact on problem-solving and seeking social support coping strategies, whereas negative emotions had a higher impact on avoidance coping strategy. Both positive and negative emotions had positive relationships with inspiration, but positive emotions had a higher impact than negative ones. The indirect effects of emotions on problem-solving and social support coping strategies through inspiration were significantly positive, while the avoidance coping strategy was not influenced by the experience of inspiration.Conclusion: The results suggest that being inspired in both positive and negative emotions is positively related to approach coping strategies in adverse situations such as COVID-19, with the effect patterns slightly differing between Chinese participants and their Western counterparts. This study highlights the importance of inspiration experience as a motivational state that can help individuals bring newly acquired ideas into fruition, especially during times of difficulty. By understanding the role of inspiration in the context of adversity, public health systems can better assist individuals in different societies to cope with the challenges they face.Keywords: COVID-19, coping, inspiration, emotions

Shanshan Wang, Ying Hua, Jun Liu, Zhifan F Huang, Jeffrey W Clymer, Crystal D Ricketts, Jin Hao Ethicon, Inc, Cincinnati, OH, USACorrespondence: Jeffrey W Clymer, Ethicon, Inc, 4545 Creek Road, Cincinnati, OH, 45242, USA, Email jclymer@its.jnj.comBackground: Design of surgical staplers continues to advance with more consistent staple formation that can lead to higher leak pressures and lower rates of leak along the staple line. This study was performed to compare the Ethicon Echelon™+ Stapler with Thunderbird reloads to two other currently available commercial staplers, Reach Anzhi and Fulbright Lunar with corresponding reloads.Methods: The rate of malformed staples for three staplers was determined in porcine stomach (3.0– 3.3 mm thickness) via CT scanning. Staple line air leak pressures in bronchial tissue (3.0– 3.3 mm) and fluid leak pressures in colon (1.3– 1.7 mm) were measured and compared to a standard success criterion for both tissues.Results: The rate of malformed staples in gastric tissue for Echelon+ was more than 90% lower than for the two other commercial staplers (p < 0.001). In bronchus, Echelon+ had 56% higher air leak pressures than Reach Anzhi (p < 0.001) and was not significantly different from Fulbright Lunar. In colon, Echelon+ had over twice the fluid leak pressures of the comparators (p < 0.001).Conclusion: The Echelon+ Stapler with Thunderbird reloads exhibited a low rate of malformed staples, and its staple lines withstood high leak pressures in both thick and thin tissues. Clinical studies are needed to confirm that these observed benefits carry over into actual practice.Keywords: stapler, endoscopic, burst pressure, malformed staples, leaking

Yongkang Liu,1 Cuiping Yuan,1 Xiao Chen,1 Xiaokun Fang,1 Jingru Hao,1 Maodong Zhou,1 Xin Sun,1 Minghua Wu,2 Zhongqiu Wang1 1Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Encephalopathy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Zhongqiu Wang, Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China, Tel/Fax +86 25-86618472, Email zhqwang2012@126.com Minghua Wu, Department of Encephalopathy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China, Tel/Fax +86 25-86618472, Email yfy0069@njucm.edu.cnPurpose: White matter hyperintensities (WMH) are the common marker of cerebral small vessel disease (CSVD). Dyslipidemia plays a notable role in the pathogenesis of CSVD. However, the relationship between dyslipidemia and WMH is poorly elucidated. This study aims to investigate the association between serum lipid fractions and WMH in patients with acute ischemic stroke (AIS).Patients and Methods: A total of 901 patients with AIS were included in this study. The burden of WMH, including deep white matter hyperintensities (DWMH), periventricular white matter hyperintensities (PVWMH), and total WMH load, were evaluated on magnetic resonance imaging (MRI) by the Fazekas scale. All the WMH burden were set as dichotomous variables. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were collected. The association of serum lipid fractions with WMH burden was analyzed using univariate and multivariate logistic regression models.Results: The average age of the participants was 67.6± 11.6 years, and 584 cases (64.8%) were male. About 33.5% (n = 302) patients were smoker, and 23.5% (n = 212) patients had a history of alcohol consumption. The proportion of previous diabetes, ischemic cardiomyopathy and hypertension was 39.0% (n = 351), 21.2% (n = 191) and 75.9% (n = 684), respectively. The average of serum HDL-c, TC, TG, LDL-c levels for all participants were 1.26 ± 0.28 mmol/l, 4.54 ± 1.06 mmol/l, 1.67 ± 1.09 mmol/l, 3.08 ± 0.94 mmol/l. There were no statistical associations between HDL-c, TG, TC, LDL-c and each type of WMH burden (P > 0.05) in multivariate logistic regression analysis. Similar findings were found in subgroup analysis based on gender classification.Conclusion: Serum lipid levels were not associated with the presence of any type of WMH in patients with AIS.Keywords: white matter hyperintensities, HDL-c, triglyceride, total cholesterol, LDL-c, acute ischemic stroke

Liujiazi Shao,1 Yang Liu,2 Junqiang Hao,1 Jiayi Li,1 Hongyu Wang,1 Fu-Shan Xue,1 Bijia Song,1 Lei Wan1 1Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 2Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of ChinaCorrespondence: Bijia Song, Email songbijia@163.comObjective: Our study aimed to demonstrate that the combination of sevoflurane inhalation with continuous intravenous anesthesia can effectively reduce the dosage of muscle relaxants, shorten extubation time under anesthesia while meeting the requirements of laparoscopic deep neuromuscular block (dNMB) in obese patients. Additionally, we sought to assess the potential reduction in postoperative residual muscle relaxants.Methods: Fifty-nine patients were randomly assigned. Anesthesia-related variables, such as anesthetics dosages, muscle relaxant effective time, clinical muscle relaxant time, muscle relaxant in vivo action time, muscle relaxant recovery time, body movement times, and extubation duration were recorded. Surgery-related variables (the Leiden-Surgical Rating Scale (L-SRS), duration of the procedure) were recorded. Pain was measured using the visual analog scale (VAS) score before leaving the PACU. The duration of the PACU stay and patients’ satisfaction levels in the PACU were also recorded.Results: Patients who inhaled sevoflurane during the operation required a lower dosage of muscle relaxant to achieve the same deep neuromuscular block (dNMB) effect. The time from stopping the rocuronium pump to T1 recovery of 90% was shorter, and the time for T1 to recover from 25% to 75% was faster among patients who inhaled sevoflurane during the operation. Furthermore, the sevoflurane combined with continuous intravenous anesthesia group exhibited a shorter extubation time for obese patients undergoing laparoscopic bariatric surgery, along with a reduced risk of experiencing hypoxemia and a shorter observation time in the PACU.Conclusion: Inhaling sevoflurane combined with continuous intravenous anesthesia during the operation effectively reduces the dosage of muscle relaxant required to achieve the same deep neuromuscular block (dNMB) effect. Additionally, this approach significantly shortens the extubation time for obese patients undergoing laparoscopic bariatric surgery and reduces the risk of experiencing hypoxemia, along with reducing the observation time in the PACU.Keywords: obese, laparoscopy bariatric surgery, rocuronium, sevoflurane, deep neuromuscular block

Xiaoyu He,1,2 Yu Luo,2 Jianan Hao,1,2 Rui Hu,1,2 Xiaoyue Yang,1,2 Luping Ren2 1Graduate School, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Luping Ren, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, People’s Republic of China, Tel +86 311 859 889 75, Email renluping1122@163.comPurpose: Diabetes is an important contributor to the progression of atherosclerosis (AS). We aimed to investigate the correlation between ketosis episodes and lipid-related parameters in patients with new-onset ketosis-prone type 2 diabetes (KPT2D), further attempting to assess the impact of ketosis episodes on AS.Patients and Methods: A cross-sectional study of 147 subjects with new-onset diabetes was performed, including 65 KPT2D subjects (KPT2D group) and 82 non-ketotic type 2 diabetes (T2D) (T2D group) subjects. Anthropometric and biochemical parameters were measured in all subjects. Calculation of atherogenic index of plasma (AIP) by traditional lipid parameters.Results: The AIP (P = 0.008) level and the percentage of AIP ≥ 0.24 (P = 0.026) in subjects with KPT2D were higher than in subjects with T2D. The apoA1 (P = 0.001) levels were significantly lower in patients with KPT2D than in patients with T2D. In the KPT2D group, plasma ketones were positively correlated with AIP (P = 0.023) and negatively correlated with apoA1 (P = 0.002). Univariate logistic regression suggested that plasma ketone (OR = 1.704, P = 0.040) was an important related factor for the AS in subjects with KPT2D. Multiple linear regression suggested plasma ketone was significantly positive with AIP (β = 0.437, P = 0.020). In multiple linear regression analysis suggests that apolipoprotein A1 (β = – 0.335, P = 0.033) is strongly associated with ketotic episodes in newly diagnosed ketosis-prone type 2 diabetic patients.Conclusion: Ketosis episodes in patients with KPT2D were significantly and positively associated with elevated AIP levels and reduced apoA1 levels. Frequent ketosis episodes may accelerate the progression of AS.Keywords: ketosis onset, ketosis-prone type 2 diabetes, lipid metabolism, atherosclerosis, atherogenic index of plasma

Can Chang,1 Huan Wang,1 Lianjun Zhang,1 Junling Hao,1 Xiaoning Wang,1 Yaoyao Wang,2 Fei Qi,2 Jingwei Lou,2 Jiangman Zhao,2 Junying Dong1 1Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Heze Branch, Heze, Shandong, 274000, People’s Republic of China; 2Shanghai Zhangjiang Institute of Medical Innovation, Shanghai Biotecan Pharmaceuticals Co., Ltd, Shanghai, 201204, People’s Republic of ChinaCorrespondence: Junying Dong, Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Heze Branch, Caozhou Road 2888, Heze, Shandong, 274000, People’s Republic of China, Tel +86- 13723908695, Email dongjunying2023@163.com Jiangman Zhao, Shanghai Zhangjiang Institute of Medical Innovation, Shanghai Biotecan Pharmaceuticals Co., Ltd, Zhangheng Road 180, Shanghai, 201204, People’s Republic of China, Tel +86- 18817517482, Email zhaojiangman86@163.comPurpose: Severe pneumonia causes the highest mortality rate in immunocompromised patients. This study aimed to investigate the pathogen diagnostic efficacy of metagenomic next-generation sequencing (mNGS) using sputum sample in patients with pneumonia according to patients’ disease severity and immune conditions.Patients and Methods: A total of 180 patients suffering from pneumonia were recruited, and sputum samples were collected in duplicate for pathogen detection by both conventional microbiological tests (CMT) and mNGS. Then, the performance of pathogen identification was examined between two methods, according to disease severity and patients’ immune status.Results: In comparison to CMT, mNGS had higher positivity rates in all patients with pneumonia (85.0% vs 62.2%, P=9.445e-07). The most commonly detected microorganism in sputum of pneumonia patients was Acinetobacter baumannii (42/180, 23.3%) in bacterum level, Candida albicans in fungus level (44/180, 24.4%), and Human herpesvirus 1 (39/180, 27.5%) in virus level. However, for mNGS results, Candida albicans in 34.9% of positive patients, and Human herpesvirus 1 in 7.7% of positive cases were confirmed as pathogens causing pneumonia. Acinetobacter baumannii detected by mNGS in 75% of positive patients was diagnosed as pathogen of pneumonia. The microorganism profile of sputum mNGS differed according to disease severity and immune status of patients. Pneumocystis jirovecii was more likely to infect immunocompromised patients (P=0.002). Pseudomonas aeruginosa (14.8% vs 0.0%, P=0.008) and Human herpesvirus 1 (26.1% vs 5.3%, P=0.004) had higher infection rate in patients with severe pneumonia compared with non-severe cases. mNGS had overwhelming advantages over CMT in detecting a lot of microorganisms including Streptococcus pneumoniae, Enterococcus faecium, Pneumocystis jirovecii, and majority of viruses.Conclusion: mNGS is a complementary tool of CMT for detecting suspected pathogens for patients with lower respiratory infections. The interpretation of opportunistic pathogens identified by mNGS is challenging, and needs comprehensive consideration of sequencing data and clinical factors.Keywords: lower respiratory infections, severe pneumonia, immunocompromised patient, conventional microbiological test, metagenomic-next generation sequencing

Xiaonan Sun,1 Zhichao Yuan,1 Lu Zhang,1 Min Ren,2 Jing Yang,2 Yidan Xu,1 Jiqing Hao1 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Breast Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of ChinaCorrespondence: Jiqing Hao, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, People’s Republic of China, Email haojiqing@ahmu.edu.cnPurpose: Elucidation of the oncogenic role of SLC35A2 in human tumors and the potential function and clinical significance in breast cancer.Methods: Pan-cancer analysis was performed via various bioinformatics tools to explain the pathogenic role of SLC35A2. A prognostic nomogram was also developed based on the SLC35A2 expression and clinicopathological characteristics in breast cancer patients. In addition, the role of SLC35A2 was validated in breast cancer by in vivo and in vitro experiments.Results: SLC35A2 expression is increased in 27 tumor types, and its high expression is substantially correlated with poor prognosis in patients with a variety of cancers. Receiver operating characteristic (ROC) curves showed that SLC35A2 expression levels could accurately distinguish most tumor tissues from normal tissues. High SLC35A2 expression was linked to increased immune infiltration in myeloid-derived suppressor cells (MDSC), as well as immune checkpoints, ferroptosis-related genes, tumor mutational burden (TMB), and microsatellite instability (MSI). SLC35A2 may be involved in tumorigenesis by regulating the glycosylation process. Furthermore, multivariate Cox analysis showed that SLC35A2 was an independent prognostic factor for breast cancer. And the nomogram model had good predictive accuracy for the prognosis of breast cancer patients. Meanwhile, cellular experiments demonstrated that knockdown of SLC35A2 could significantly inhibit the proliferation, migration and invasion of breast cancer cells, while increasing the protein level of E-cadherin and decreasing N-cadherin. A nude mouse xenograft model showed that inhibition of SLA35A2 expression could significantly inhibit tumor growth.Conclusion: SLC35A2 has good diagnostic and prognostic values in multiple cancers and is closely related to tumor immune infiltration. In addition, SLA35A2 as an oncogene in breast cancer may be involved in the progression of epithelial mesenchymal transition (EMT).Keywords: SLC35A2, pan-cancer, breast cancer, prognostic, tumor microenvironment, EMT

Chen Li,1,&ast; Jun Hao,2,&ast; Chuangshi Wang,2 Jie Yang,1 Yitian Zheng,1 Kuo Zhang,3 Wen Hui,4 Xiangbin Meng,1 Jun Gao,1 Wei Li,2 Yi-Da Tang1,5 1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, People’s Republic of China; 2Medical Research and Biometrics Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Science and Technology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Yi-Da Tang, Email liwei@mrbc-nccd.com; tangyida@bjmu.edu.cnObjective: The incidence rate of thyroid diseases increased worldwide. This study aims to overview the changing landscape of drug clinical trials on thyroid disease during 2009– 2022.Methods: The detailed information of thyroid disease drug trials registered on the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform for Drug Clinical Studies was searched and collected. The thyroid drug clinical trials were analyzed by the characteristics, time trends, indications, and geographical distribution.Results: Sixty-five thyroid disease drug clinical trials were launched from 2009 to 2022 in China, which included 21 trials in nontumorous thyroid disease and 44 trials in thyroid carcinoma. The number of registered trials of thyroid diseases including thyroid carcinoma and nontumorous thyroid disease increased steadily from 2009 to 2020. Bioequivalence studies accounted for the largest proportion (32[49.2%]), while phase I and Phase II studies both only accounted for 18.5% (12/65). A significant difference was observed in the trials phase, and randomization between thyroid carcinoma and nontumorous thyroid disease. In terms of clinical indications and drug mechanisms, the number of trials in multi-target tyrosine kinase inhibitors for thyroid carcinoma (n=35) ranked first, followed by thyroid hormone for hypothyroidism (n=7), thyrotropin for thyroid carcinoma (n=6). Sixty-five trials were led by 36 principal investigator (PI) units, and more than 30% of PI-leading units were located in Shanghai (n=7) and Beijing (n=4).Conclusion: During the past 13 years, the development of thyroid diseases drugs trials has achieved certain progress in thyroid carcinoma, especially the molecular targeted therapy, yet the development of drug trials on nontumorous thyroid disease was very slow.Keywords: thyroid disease, thyroid carcinoma, nontumorous thyroid disease, China, drug clinical trial

Mingjun Hu,1– 4 Jie Wei,1– 3 Jie Hao,1– 3 Tianbo Jin,1– 3 Bin Li1– 3 1College of Life Sciences, Northwest University, Xi’an, Shaanxi Province, People’s Republic of China; 2Provincial Key Laboratory of Biotechnology of Shaanxi, Northwest University, Xi’an, Shaanxi Province, People’s Republic of China; 3Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, Shaanxi Province, People’s Republic of China; 4Department of Neurosurgery, Xi’an Chang’an District Hospital, Xi’an, Shaanxi Province, People’s Republic of ChinaCorrespondence: Mingjun Hu, College of Life Sciences, Northwest University, &num;229, Taibai North Road, Xi’an, Shaanxi Province, 710069, People’s Republic of China, Tel +86-15339228629, Email slhmj@tom.comBackground: Glioma is the main pathological subtype of brain tumors with high mortality.Objective: This study aimed to elucidate the correlation between TREM1 variants and glioma risk in the Chinese Han population.Methods: Genotyping of six variants of TREM1 was completed by Agena MassARRAY platform in 1061 subjects (503 controls and 558 glioma patients). The relationship between TREM1 polymorphisms and glioma risk was calculated using the logistic regression model, with odds ratio (OR) and 95% confidence intervals (CIs). A multifactor dimensionality reduction (MDR) method was performed to assess SNP–SNP interactions to predict glioma risk.Results: In this research, overall analysis illustrated an association between TREM1 rs9369269 and an increased risk of glioma. Rs9369269 was also related to the risk of glioma in patients aged ≤ 40 years and females. Subjects with rs9369269 AC genotype were likely to obtain glioma compared to people with CC genotype (patients with astroglioma vs healthy people). Compared to TT genotype carriers, carriers with AT genotype of rs1351835 were significantly associated with overall survival (OS).Conclusion: Taken together, the study identified the association between TREM1 variants and glioma risk and TREM1 variants were significantly associated with the prognosis of glioma. In the future, larger samples are needed to verify the results.Keywords: glioma, TREM1, single nucleotide polymorphisms, risk

Meng-Yu Fu,1 Jie Hao,2 Lun-Hui Ye,3 Wei Jiang,2 Ying-Wen Lv,1 Jie-Liang Shen,2 Tao Fu1 1Department of Orthopaedics, The Thirteenth People’s Hospital of Chongqing (The Geriatric Hospital of Chongqing), Chongqing, 400053, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Department of Anesthesiology, The Thirteenth People’s Hospital of Chongqing (The Geriatric Hospital of Chongqing), Chongqing, 400053, People’s Republic of ChinaCorrespondence: Jie-Liang Shen; Tao Fu, Email 18996078008@qq.com; cqsdssrmyyft@163.comBackground: Since the application of ultrasound-guided erector spinae plane block (ESPB) in 2016, the approach has been gradually applied to perioperative analgesia in various surgeries. In recent years, more and more studies have focused on the effect of ESPB in perioperative analgesia of lumbar spinal surgery, but its clinical effect remains controversial.Objective: This systematic review and meta-analysis was designed to explore the efficacy and safety of ESPB used for perioperative pain management in lumbar spinal surgery.Methods: The Pubmed, Web of Science, Cochrane Library, and EMBASE databases were comprehensively searched for relevant articles from inception to March 2022. Randomized controlled trials (RCTs) comparing ESPB with placebo or without ESPB in lumbar spinal surgery were included. The Review Manager 5.3 software was employed for this meta-analysis.Results: Nineteen RCTs with 1381 participants were included for final analysis. ESPB group exhibited lower intraoperative consumption of sufentanil and remifentanil, lower total opioid consumption within 24 h and 48 h after surgery, lower incidence of rescue analgesia, longer time to first rescue analgesic and lower number of PCA button presses compared to the control group (P< 0.05). Moreover, the ESPB group had significantly lower pain scores at rest and on movement within 48 h after surgery compared with the control group (P< 0.05). In terms of opioid-related adverse reactions, ESPB reduced the incidence of postoperative nausea, vomitting, somnolence and itching in comparison to the control group (P< 0.05). ESPB-related serious complications were not reported in included studies.Conclusion: This meta-analysis demonstrated that ESPB used in lumbar spinal surgery was effective in relieving postoperative pain, decreasing the perioperative consumption of opioids, as well as decreasing the incidence of postoperative opioid-related adverse reactions.Keywords: erector spinae plane block, lumbar spinal surgery, perioperative analgesia, randomized controlled trial, meta-analysis

Yue Fang,1,2 Zhichao Yuan,1 Hao Zhang,1 Peng Wang,3 Jiqing Hao1 1Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Intern of Oncology, Hefei Cancer Hospital, Chinese Academy of Sciences (CAS), Hefei, People’s Republic of China; 3Department of Anesthesiology, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Jiqing Hao, Email haojiqing@ahmu.edu.cnPurpose: Heat shock protein 90α (HSP90α) is highly expressed in tumors, and predicts tumor progression. This study analyzed the correlation between the expression level of HSP90α in the serum and the prognosis of patients with lung adenocarcinoma.Patients and methods: The medical records of patients with 228 lung adenocarcinoma from September 2015 to December 2021 were analyzed. HSP90α expression in the patients’ serum was detected by ELISA and the cut-off value (93.76 ng/mL) was determined according to the ROC curve, then the patients were divided into high- and low-level groups. The differences in the medical records of the two groups were compared using the X2 test, and Univariate and multivariate Cox regression analyses showed that serum HSP90α level were independent risk factors for both PFS and OS (P < 0.05).Results: HSP90α was positively correlated with TNM staging (P < 0.01) by One-way analysis of variance. The results of the correlation analysis and the Kaplan–Meier survival curve showed that the expression levels of HSP90α and CEA of patients were positively correlated (R=0.54, P < 0.001), and patients with high HSP90α and CEA levels had the worst OS (P < 0.001).Conclusion: HSP90α expression is negatively correlated with the prognosis of patients with lung adenocarcinoma and is a potential prognostic marker.Keywords: heat shock protein 90α, lung adenocarcinoma, prognosis, CEA

Jingjing Hao, Jingyuan Liu, Lin Pu, Chuansheng Li, Ningning Yin, Ang Li Department of Critical Care Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Ang Li, Email liang@ccmu.edu.cnBackground: Respiratory failure in acquired immunodeficiency syndrome (AIDS) patients was the leading cause of intensive care unit (ICU) admission in our center. We aimed to describe the pulmonary infections and outcomes for respiratory failure in AIDS patients.Methods: A retrospective study was conducted on AIDS adult patients with respiratory failure who were admitted to the ICU in Beijing Ditan hospital, China, from January 2012 to December 2021. We investigated pulmonary infections complicated by respiratory failure in AIDS patients. The primary outcome was ICU mortality, and a comparison between survivors and nonsurvivors was performed. Multiple logistic regression analysis was used to identify predictors of ICU mortality. The Kaplan-Meier curve and Log rank test were used for survival analysis.Results: A total of 231 AIDS patients were admitted to ICU with respiratory failure over a 10-year period with a male predominance (95.7%). Pneumocystis jirovecii pneumonia was the main etiology of pulmonary infections (80.1%). The ICU mortality was 32.9%. In multivariate analysis, ICU mortality was independently associated with invasive mechanical ventilation (IMV) [odds ratio (OR), 27.910; 95% confidence interval (CI, 8.392– 92.818; p = 0.000) and the time before ICU admission (OR, 0.959; 95% CI, 0.920– 0.999; p = 0.046). In the survival analysis, patients with IMV and later admission to ICU had a higher probability of mortality.Conclusion: Pneumocystis jirovecii pneumonia was the primary etiology for respiratory failure in AIDS patients admitted to the ICU. Respiratory failure remains a severe illness with high mortality, and ICU mortality was negatively associated with IMV and later admission to ICU.Keywords: acquired immunodeficiency syndrome, AIDS, respiratory failure, pulmonary infections, ICU mortality

Yu Luo,1 Cuiyu Wang,1,2 Tian Zhang,1,3 Xiaoyu He,1,4 Jianan Hao,1,4 Andong Shen,3,5 Hang Zhao,1 Shuchun Chen,1 Luping Ren1 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 2Graduate School, Hebei North University, Zhangjiakou, People’s Republic of China; 3Graduate School, North China University of Science and Technology, Tangshan, People’s Republic of China; 4Graduate School, Hebei Medical University, Shijiazhuang, People’s Republic of China; 5Gastroenterology Department, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Luping Ren, Email renluping1122@163.comPurpose: Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are frequently co-occurring diseases. Liver fibrosis (LF), with increasing incidence, has a prognostic value for NAFLD mortality. Our study aimed to investigate the relevant factors for FL in T2DM individuals with NAFLD.Patients and Methods: A total of 565 T2DM patients with NAFLD from Hebei General Hospital participated in the study. Patients underwent an abdominal ultrasound, a questionnaire and laboratory tests. The fibrosis-4 index (FIB-4) was used to evaluate LF, with FIB ≥ 1.3 indicating LF and FIB ≥ 2.67 indicating F3-4 fibrosis.Results: Compared with NLF group, LF group had higher levels of systolic blood pressure (SBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (GGT). The glomerular filtration rate (GFR), low-density lipoprotein cholesterol (LDL), glycated hemoglobin (HbA1c), and platelets (PLT) in LF patients were lower than those without LF. Patients with LF were older than those without LF. ALT, AST, and GGT in patients with severe LF were higher than those with mild LF, while platelet was lower. Age, SBP, duration of diabetes, ALT, AST, and GGT were positively correlated with FIB-4, while eGFR, TC, LDL, and HbA1c were negatively correlated with FIB-4. Logistic regression showed that age, SBP, ALT, GGT, LDL, and PLT were independently associated with LF.Conclusion: For T2DM patients combined with NAFLD, older age, higher SBP, higher ALT, higher GGT, lower LDL, and lower PLT were relevant factors for LF.Keywords: type 2 diabetes mellitus, non-alcoholic fatty liver disease, fibrosis-4 index, liver fibrosis

Jianan Hao,1,2,&ast; Yichao Wang,1,&ast; Lijing Huo,3 Tiantian Sun,1 Yunfeng Zhen,1 Zhe Gao,1 Shuchun Chen,1 Luping Ren1 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Graduate School of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Laboratory Department, Hebei General Hospital, Shijiazhuang, Hebei, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Luping Ren, Endocrinology Department, Hebei General Hospital, 348, Heping West Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email renluping1122@163.comObjective: We aimed to examine the association between bone morphogenetic protein-9 (BMP-9) and type 2 diabetes mellitus (T2DM) in conjunction with non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR) and to identify evidence supporting the potential role of BMP-9 in the clinical prevention and treatment of T2DM in conjunction with NAFLD.Methods: One hundred and twenty subjects were included in this study. We sorted all of the subjects into four groups of equal size (n=30 each). A trained expert assessed the height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) of the subjects and computed the body mass index (BMI). All subjects had their fasting blood glucose (FBG), fasting insulin (FINS), serum BMP-9, and biochemical indices assessed.Results: Significant variations were observed in BMI, SBP, DBP, ALT, TC, TG, HDL-C, LDL-C, ApoB, FBG, FINS, HOMA-IR, and serum BMP-9 among the four groups (P< 0.05). The level of serum BMP-9 was positively correlated with HDL-C, while the level of serum BMP-9 was negatively correlated with BMI, SBP, DBP, ALT, TC, TG, LDL-C, FBG, FINS, and HOMA-IR. Multiple stepwise regression analyses revealed that FINS, LDL-C, HDL-C, and BMI were independent factors impacting serum BMP-9 levels (P< 0.05). Logistic regression analyses revealed that BMP-9 was a protective factor for T2DM paired with NAFLD, while HOMA-IR was a risk factor.Conclusion: Serum BMP-9 levels are significantly lower in the T2DM+NAFLD group when compared to other groups, and BMP-9 is an independent risk factor for T2DM paired with NAFLD.Keywords: bone morphogenetic protein-9, type 2 diabetes mellitus, non-alcoholic fatty liver disease, insulin resistance, glucose and lipid metabolism

Yu Luo,1 Jianan Hao,1,2 Xiaoyu He,1,2 Cuiyu Wang,1 Hang Zhao,1 Zhimei Zhang,1 Liqun Yang,1 Luping Ren1 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 2Graduate School, Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Luping Ren, Hebei General Hospital, No. 348, Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel +18633021149, Fax +86 311 85988406, Email renluping1122@163.comPurpose: The triglyceride–glucose index (TyG) is positively correlated with serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). However, whether this relationship exists in non-obese T2DM patients remains unknown. The study investigated the relationship between TyG and SUA in Chinese non-obese T2DM patients and examined the prognostic value of TyG in hyperuricemia (HUA).Patients and Methods: In total, 719 T2DM patients who were not obese were enrolled from among those who visited the Hebei General Hospital. The patients were categorized into groups according to their SUA levels. The relationship between TyG and clinical parameters was examined through correlation analysis. To consider covariates and examine the independent impact of TyG on HUA, logistic regression was performed. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of TyG and homeostasis model assessment of insulin resistance (HOMA-IR) for HUA.Results: The HUA prevalence was 12.10%. TyG was statistically different among the four SUA groups, with lower TyG levels in the Q1, Q2, and Q3 groups than that in the Q4 group. TyG was positively correlated with SUA (r = 0.176, P < 0.001). Logistic regression exhibited that TyG and SUA were independently correlated (OR = 2.427, 95% CI = 1.134-5.195, P = 0.022) even after adjustment for confounding factors. The ROC curve showed that the predictive value of TyG for HUA was higher than that of HOMA-IR (AUROC = 0.613, P = 0.001).Conclusion: TyG was positively correlated with SUA in non-obese T2DM patients. TyG may better predict HUA in non-obese T2DM patients than HOMA-IR.Keywords: type 2 diabetes mellitus, insulin resistance, uric acid, hyperuricemia, TyG, HOMA-IR, inflammation

Xinqun Cheng,1,2,&ast; Lingjia Fan,3,&ast; Jiabei Hao,4 Honghou He,4 Jincheng Yan,1,2 Yanbin Zhu1,2 1Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, People’s Republic of China; 2Hebei Orthopedic Research Institute, Key Laboratory of Biomechanics of Hebei Province, Shijiazhuang, 050051, People’s Republic of China; 3Department of Orthopadic Surgery, Shandong First Medical University, Jinan, 250000, People’s Republic of China; 4Basic Medical College, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jincheng Yan; Yanbin Zhu, Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, People’s Republic of China, Email Yandoctor163@163.com; zhuyanbin111@126.comBackground: Deep vein thrombosis (DVT) is a devastating complication in geriatric patients before hip fracture surgery, and the predictive value of red cell distribution width (RDW) and high-density lipoprotein cholesterol (HDL-C) for DVTs after hip fracture remains to be established. This study aimed to assess the predictive value of RDW, HDL-C, and RDW-to-HDL-C ratio (RHR) in preoperative DVTs screening.Methods: We retrospectively analyzed the data of geriatric patients (≥ 65 years old) admitted for hip fracture surgery between 2015 and 2020. The receiver operating characteristic (ROC) curve and related parameters were used to evaluate the predictive value of the biomarkers. Patients were divided into two groups according to the cutoff value of RHR, and propensity score matching (PSM) and subgroup analyses were performed to assess the true correlations between RHR and DVT.Results: Among 2566 eligible patients included, we identified RDW with the area under ROC curve (AUC) of 0.532, cut-off value of 15.89, specificity of 88.2%, sensitivity of 18.2%, HDL-C with AUC of 0.574, cut-off value of 1.20, specificity of 55.6%, sensitivity of 59.3%, and RHR with AUC of 0.578, cut-off value of 13.45, specificity of 71.3%, sensitivity of 43.4%. RHR (> 13.45) was independently associated with 1.54-fold risk (95% CI: 1.11– 2.14, P=0.011) of DVTs among the post-PSM cohort. And compared with the counterparts, the relative risk of RHR associated with DVT was higher in the subgroups of aged 65– 79 years (1.61 vs 1.45), non-hypoproteinemia (2.70 vs 1.29), non-diabetic (1.58 vs 1.41), non-hypertension (2.40 vs 1.06), ASA score I-II (2.38 vs 1.04), and femoral neck fracture (1.70 vs 1.50).Conclusion: RDW, HDL-C and RHR were valuable biomarkers in predicting preoperative DVTs in geriatric patients with hip fracture, and RHR would be more efficient in the subgroups of younger age, better medical condition or femoral neck fracture.Keywords: geriatric patients, hip fracture, deep vein thrombosis, red cell distribution width, high-density lipoprotein cholesterol

Miaomiao Li,1,&ast; Yue Yuan,1,&ast; Xue Han,2 Xinjuan Liu,1 Weizhen Zhang,2 Jianyu Hao1 1Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianyu Hao, Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8, South Road of Workers Stadium, Chaoyang District, Beijing, 100020, Email haojianyu@ccmu.edu.cn Weizhen Zhang, Department of Physiology and Pathophysiology, Peking University Health Science Center, No. 38, Xueyuan Road, Haidian District, Beijing, 100191, Email weizhenzhang@bjmu.edu.cnBackground: Chronic pancreatitis (CP) is a long-term inflammatory disease of the pancreas that can be caused by various pathogenic factors. Oxidative stress (OS), which is associated with several pancreatic diseases, can induce pancreatic stellate cell (PSC) activation, leading to pancreatic fibrosis. Given the inefficacy of existing treatments for CP, in this study, our objective was to evaluate the therapeutic effect of the antioxidant, mitoquinone (MitoQ).Methods: First, in vivo, we established a CP mouse model via the repeated injection of cerulein. Mice in the MitoQ group simultaneously received MitoQ daily. After 4 weeks of cerulein injection, pancreatic tissues from mice were evaluated by morphological changes and the expression of fibrosis markers. Further, OS in the collected pancreatic tissue samples was evaluated by determining the level of malondialdehyde (MDA) as well as the expression levels and activities of antioxidants. Furthermore, in vitro, the effect of MitoQ on human PSCs (hPSCs) was evaluated based on PSC activation markers and fibrotic phenotypes, and OS in these treated hPSCs was evaluated by measuring reactive oxygen species (ROS), MDA, and antioxidant levels.Results: In vivo, MitoQ alleviated pancreatic fibrosis and inhibited OS in the cerulein-induced murine CP model. In vitro, it inhibited PSC activation as well as the subsequent development of the profibrogenic phenotypes by balancing out the levels of free radicals and the intracellular antioxidant system.Conclusion: MitoQ is a potential candidate for CP treatment.Keywords: chronic pancreatitis, pancreatic stellate cells, pancreatic fibrosis, oxidative stress, mitochondria-specific antioxidant, MitoQ, superoxide dismutase

Lu Zhang,1 Yue Fang,1 Jianghao Xing,1 Hao Cheng,2 Xiaonan Sun,1 Zhichao Yuan,1 Yidan Xu,1 Jiqing Hao1 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Jiqing Hao, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, 81 Meishan Road, Hefei, 230022, People’s Republic of China, Tel +86 13965029739, Email haojiqing@ahmu.edu.cnPurpose: This study aimed to analyze the association between venous thromboembolism (VTE) and inflammatory markers like systemic immune-inflammation index (SII) and prognosis nutritional index (PNI), and to evaluate their efficacy for the diagnosis of VTE in patients with gastrointestinal malignancies.Patients and Methods: A total of 1326 patients with the initial diagnosis of gastrointestinal cancer in the First Affiliated Hospital of Anhui Medical University (AHMU) were enrolled in the training cohort. Univariate and multivariate analysis was used to pinpoint independent predictors of VTE, which were eventually visualized as the nomogram models. The Akaike Information Criterion (AIC) was used to screen the best model. The receiver operating characteristic curve (ROC) and the clinical decision curve analysis (DCA) were utilized to evaluate the models’ predictive performance in the training queue and another external sample of 250 patients at the Second Affiliated Hospital of AHMU.Results: A total of 476 patients were complicated with VTE in the training cohort. Multifactorial analysis of clinical characteristics and inflammatory markers showed that PNI, SII, age, tumor location, and therapy were independent risk factors of VTE, visualized as model A. Another model B was constructed by adding coagulation markers to the previous analysis. Model B was the best prediction model with the minimum AIC value, followed by model A with an AUC of 0.806 (95% CI 0.782∼ 0.830) which was similar to model B’s 0.832 (95% CI 0.810∼ 0.855) but significantly higher than the currently widely used Khorana score’s 0.592 (95% CI 0.562∼ 0.621) and the CATS score’s 0.682 (95% CI 0.653∼ 0.712). The external verification yielded similar findings, with the AUC being 0.792 (95% CI 0.734∼ 0.851), 0.834 (95% CI 0.778∼ 0.890), 0.655 (95% CI 0.582∼ 0.729), and 0.774 (95% CI 0.699∼ 0.849) respectively. The DCA curves demonstrated that new models had excellent usefulness in screening patients with a high VTE risk.Conclusion: The SII and PNI were simple and viable inflammatory markers associated with VTE, and the nomogram based on them and clinical features had a meaningful clinical utility for VTE in patients with gastrointestinal malignancies.Keywords: venous thromboembolism, gastrointestinal cancers, inflammation, systemic immune-inflammation index, nomogram

Yun Yan,1,&ast; Lei Yang,2,&ast; Xiaoli Li,3,&ast; Jian Hao,4,&ast; Bijue Wang,4 Dan Wang,5 Junning Wang3 1Department of Orthopedics and Traumatology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China; 2Department of Osteoporosis, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China; 3Department of Respiratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China; 4Xi’an Public Health Center, Xi’an, Shaanxi, 710200, People’s Republic of China; 5Department of Pathology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710054, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junning Wang, Department of Respiratory, Honghui Hospital, Xi’an Jiaotong University, No. 555, Youyi East Road, Nanshaomen, Xi’an, Shaanxi, 710054, People’s Republic of China, Tel/Fax +86 02962818354, Email wangjunningde@163.comPurpose: At present, it has been found that managing patients with a redetected positive RNA test after recovery from foreign-imported coronavirus disease 2019 (COVID-19) cases in China is challenging. The purpose of the current study was to describe the clinical characteristics of these patients.Methods: This retrospective cohort study included 137 COVID-19 patients who were discharged from the Xi’an Public Health Center from 28 July 2020 to 31 December 2021. We compared the clinical characteristics between positive retest patients and non-positive retest patients.Results: 137 COVID-19 patients entered our study, 27 (19.7%) cases of COVID-19 with a redetected positive RNA test by the end of the follow-up period. Fever [(n = 31 (22.6%)], cough [n = 26 (18.9%)] and sore throat [n = 20 (14.5%)] were the most common initial symptoms among the foreign-imported COVID-19 patients, and there were almost no significant differences in initial symptoms between positive retest patients and non-positive retest patients. The positive retest patients had a higher lymphocyte count (p = 0.031) and lymphocyte percentage (p = 0.007) during readmission. There were generally no significant differences in other routine blood test findings, IgG and IgM antibody responses, between positive retest patients and non-positive retest patients, or in positive retest patients over time (before, during, or after positive patient detection). After readmission, positive retest patients displayed fewer symptoms or no obvious disease progression and more sustained remission by CT imaging.Conclusion: Our findings revealed that the clinical characteristics at the time of initial diagnosis were not closely related to redetected positive RNA tests after recovery from foreign-imported COVID-19 cases. Positive retest patients had virtually no symptoms and displayed no obvious disease progression during readmission. These findings provide important information and clinical evidence for the effective management of foreign-imported COVID-19 patients during their convalescent phase.Keywords: SARS-CoV-2, COVID-19, clinical characteristics, foreign-imported cases, redetected positive RNA test

Qiuyue Feng,1,2 Jingjing Hao,3 Ang Li,3 Zhaohui Tong1 1Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Respiratory Medicine, Beijing Huairou Hospital, Beijing, 101400, People’s Republic of China; 3Department of Critical Care Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Zhaohui Tong, Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China, Email tongzhaohuicy@sina.com Ang Li, Department of Critical Care Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Email liang@ccmu.edu.cnPurpose: Pneumocystis jirovecii pneumonia (PCP) is a major cause of death in immunocompromised patients. Many risk factors for poor prognosis have been reported, but few studies have created predictive models with these variables to calculate the death rate accurately. This study created nomogram models for the precise prediction of mortality risk in human immunodeficiency virus (HIV) uninfected and HIV-infected patients with PCP.Patients and Methods: A retrospective study was performed over a 10-year period to evaluate the clinical characteristics and outcomes of PCP in HIV-uninfected and HIV-infected adults treated in Beijing, China from 2010 to 2019. Univariate and multivariate logistic regression analyses were used to identify mortality risk factors to create the nomograms. Nomogram models were evaluated by using a bootstrapped concordance index, calibration plots and receiver operating characteristic (ROC) curves.Results: A total of 167 HIV-uninfected and 193 HIV-infected PCP patients were included in the study. Pneumothorax, duration of fever after admission, CD4+ T cells ≤ 100/μL and trimethoprim-sulfamethoxazole (TMP-SMX) combined with caspofungin (CAS) treatment were independent risk factors for death in HIV-uninfected PCP patients. We derived a well calibrated nomogram for mortality by using these variables. The area under the curve was 0.865 (95% confidence interval 0.799– 0.931). Independent risk factors for death in HIV-infected PCP patients were pneumothorax, platelet (PLT) ≤ 80× 109/L, haemoglobin (HGB) ≤ 90 g/L, albumin (ALB), cytomegalovirus (CMV) coinfection and TMP-SMX combined with CAS treatment. The nomogram showed good discrimination, with a C-index of 0.904 and excellent calibration.Conclusion: The nomograms which were derived may be useful tools for the precise prediction of mortality in HIV-uninfected and HIV-infected patients, but require validation in clinical practice.Keywords: Pneumocystis jirovecii pneumonia, nomogram, HIV, HIV-uninfected, mortality

Jingchen Hao,1,&ast; Zhangrui Zeng,1,&ast; Xue Xiao,2 Yinhuan Ding,1 Jiamin Deng,3 Yueshuai Wei,1 Jinbo Liu1 1Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, People’s Republic of China; 2Department of Laboratory Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo Liu, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel/Fax +86 830 3165730, Email liulab2019@163.comBackground: Colistin is one of the few options for treating carbapenem-resistant Enterobacterales (CREs). There is little available information about the epidemic status of colistin-resistant CREs in Southern Sichuan, China. This study mainly investigated the genomic and phenotypic characteristics of an extensively drug resistant E. coli LZ00114 isolated from Luzhou, China.Materials and Methods: In 2020, LZ00114 was isolated from the urine of a patient with hydronephrosis and urinary tract infection in Luzhou, China. We assessed the resistance profile of LZ00114 in the presence and absence of the protonophore carbonyl cyano-m-chlorophenylhydrazine (CCCP) and 1-(1-naphthylmethyl)-piperazine (NMP) by antimicrobial susceptibility testing. The growth kinetics, motility, and pathogenicity of LZ00114 were determined to evaluate its microbial characteristics. In combination with whole genome sequencing (WGS) and real-time reverse transcription PCR (RT-PCR), we comprehensively analyzed the resistance mechanisms of LZ00114.Results: LZ00114 was resistant to various antimicrobial agents, including meropenem, tetracycline, ciprofloxacin, gentamicin, fosfomycin, and polymyxin B. Notably, CCCP reversed the resistance of LZ00114 to polymyxin B. LZ00114 displayed high pathogenicity in the infection model (P< 0.01) compared with the Lab-WT strain, and its growth rate and motility were not significantly different from the Lab-WT strain. WGS and conjugation revealed that LZ00114 belonged to ST410 and carried a blaNDM-5-harboring self-transmissible IncX3 plasmid and a multi-replicon IncFII/FIA/FIB plasmid carrying blaOXA-1-blaCTX-M-55-tet(B)-aac(6’)-Ib-cr-dfrA17-sul1-fosA3. Comparative genomics revealed genetic relatedness between LZ00114 and strains isolated from other regions. Furthermore, there were point mutations in pmrA (S29G, G144S), pmrB (D283G, Y358N), marR (G103S, Y137H), emrA (I219V), and emrD (G323D) of LZ00114. RT-PCR confirmed the overexpression of efflux pumps and PmrABC in LZ00114.Conclusion: This study provides valuable information for the surveillance of antimicrobial resistance and a theoretical basis for the prevention and control of colistin-resistant E. coli. There is still a need to be vigilant about the clone spread of the high-risk clone group E. coli ST410.Keywords: E. coli, antimicrobial resistance, whole genome sequencing, colistin, carbonyl cyanide m-chlorophenylhydrazine, CCCP, ST410

Zhaoyinqian Li,&ast; Jingling Xie,&ast; Jiaxin Yang, Siyi Liu, Zixuan Ding, Jingchen Hao, Yinhuan Ding, Zhangrui Zeng, Jinbo Liu Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo LiuDepartment of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Taiping Street, Luzhou, 646000, Sichuan, People’s Republic of ChinaTel +86 0830 3165730Email Liulab2019@163.comObjective: This study aimed to determine the clinical manifestations, antimicrobial resistance, molecular characteristics, and risk factors for ESKAPE pathogens infection in burn patients.Methods: A retrospective study of 187 burn patients infected with ESKAPE pathogens was conducted at the Department of Plastic and Burn Surgery of the Affiliated Hospital of Southwest Medical University (Luzhou, China) from October 2018 to June 2021. All strains were identified using a MicroScan WalkAway 96 Plus System, and antimicrobial susceptibilities were determined using the VITEK system or the disk diffusion method. The antimicrobial resistance genes of multi-drug resistant ESKAPE (MDR-ESKAPE) were detected by polymerase chain reaction (PCR). The multivariable logistic regression analysis was used to estimate the risk factors for ESKAPE infection and MDR-ESKAPE infection.Results: A total of 255 strains were isolated in various types of clinical specimens from 187 burn patients, of which 47.5% were ESKAPE pathogens (121/255). Among these, MDR-ESKAPE pathogens accounted for 55% (67/121). Additionally, aph3ʹIII, mecA, blaSHV, blaTEM, blaPDC, and blaSHV were the most prevalent genes detected in Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp., respectively. The independent risk factors for ESKAPE infection were total body surface area (TBSA) > 30– 50% (odds ratio [OR] = 10.428; 95% confidence interval [CI], 2.047 to 53.108), TBSA > 50% (OR = 15.534; 95% CI, 1.489 to 162.021), and parenteral nutrition (OR = 3.597; 95% CI, 1.098 to 11.787). No independent risk factors were found for MDR-ESKAPE infection.Conclusion: Clinical staff should be alert to the risk of nosocomial infection with ESKAPE pathogens in burn patients receiving parenteral nutrition and under TBSA > 30%. Full attention should also be paid to the ESKAPE resistance, strict adherence to infection control protocols for the rational use of antimicrobial agents, and enhanced clinical standardization of antimicrobial agents management.Keywords: burn, ESKAPE pathogens infection, antimicrobial resistance, risk factors

Shaochong Lin,1,2 Junpeng Du,3 Jun Hao,1 Xiaohua Luo,1 Han Wu,1 Huifang Zhang,1 Xinxin Zhao,1 Lida Xu,1 BaoJin Wang1,2 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Henan International Joint Laboratory of Ovarian Malignant Tumor, Zhengzhou, 450052, People’s Republic of China; 3Department of Pediatric Surgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: BaoJin WangDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No. 7, Kangfu Front Street, Erqi District, Zhengzhou, 450052, People’s Republic of ChinaTel +86 156 3927 7692Fax +86 371-66903480Email 2995269936@qq.comPurpose: Family with sequence similarity 83 (FAM83) is a newly discovered oncogene family, and the members of which can affect the prognosis of patients with malignant tumors via various mechanisms. However, the functions and molecular mechanisms of FAM83 genes in ovarian cancer (OC) have not yet been investigated. This study aimed to explore the clinical significance and prognostic value of FAM83 genes in OC.Materials and Methods: We used a series of bioinformatics databases (Oncomine, GEPIA, cBioPortal, Kaplan–Meier plotter, DAVID and TIMER) to investigate the expression status, prognostic value, genetic alteration and biological function of all eight FAM83 genes in OC. In addition, a tissue microarray cohort (TMA) comprising 99 ovarian tumor tissues and 19 normal ovarian tissues was used to validate the protein expression and clinicopathological significance of FAM83H.Results: Several datasets demonstrated the mRNA levels of FAM83A/D/E/F/H were significantly higher in OC compared with that in normal tissue. Moreover, the upregulation of FAM83D/H has been mutually confirmed in the Oncomine and GEPIA datasets. Kaplan–Meier survival analysis indicated that the FAM83D/H upregulation could predict poor prognosis of OC patients who had shorter overall survival (OS) and progression-free survival (PFS). In addition, cBioportal analysis indicated that the genetic alterations of FAM83 genes might affect the survival outcomes of patients with OC. Furthermore, KEGG analysis suggested that FAM83D/H are involved in the progression of OC through the cell cycle signaling pathway, and they had significant co-expression relationship with cell cycle-related genes. Finally, immunohistochemistry analysis confirmed the high expression of FAM83H protein in OC tissue, suggesting that its expression is positively correlated with the FIGO stage and pathological subtype of OC.Conclusion: This study elucidated the expression status and prognostic value of FAM83 genes in OC and identified that FAM83D/H might be potential targets for the prognostic monitoring and targeted therapy of OC.Keywords: FAM83s, ovarian cancer, prognosis, immunohistochemistry, biomarker

Yinfeng Liu,1,2 Jun Hao,3 Guanli Yuan,4 Mengyu Wei,1 Yuhui Bu,1 Tingting Jin,3 Li Ma1 1Department of Breast Disease Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Department of Breast Surgery, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of China; 3Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of ChinaCorrespondence: Li MaDepartment of Breast Disease Center, The Fourth Hospital of Hebei Medical University, No. 169, Tianshan Street, Shijiazhuang, Hebei, 050000, People’s Republic of ChinaTel +86 -0311-66696348Email mali1021@126.comBackground: Circadian clock genes play a crucial role in physiological and pathological processes, and their aberrant expressions were involved in various human cancers. The objective of this study was to investigate the expression level of Period circadian regulator 1 (PER1), an important circadian clock gene, and its biological roles in the development and progression of breast cancer.Methods: The expression level of PER1 in breast cancer samples was analyzed using the Oncomine database, and the correlation between PER1 expression and clinicopathologic parameters was assessed by bc-GenExMiner v4.5. In addition, Kaplan–Meier plotter database was used to determine the prognostic significance of PER1 expression for breast cancer patients. The expressions of PER1 in breast cancer tissues and cells were validated by Western blot. The loss-or-gain assay of PER1 was conducted to investigate the effects of its expression on cell proliferation, migration and invasion of breast cancer. The relationship between PER1 expression and epigenetic modifications was further explored by Western blot.Results: The results of the bioinformatics analysis revealed that the expression level of PER1 was markedly reduced in breast cancer tissues (P< 0.001), and patients with high expression of PER1 had a better overall survival (HR:0.78, 95% CI:0.63– 0.97, P=0.026) and recurrence-free survival (HR:0.83, 95% CI:0.75– 0.93, P=0.001) than those with low expression. The assay of gene loss-or-gain indicated that downregulation of PER1 expression markedly promoted cell proliferation, migration and invasion (P< 0.05), whereas these malignant phenotypes of breast cancer cells were inhibited by PER1 overexpression (P< 0.05). Further studies showed that trichostatin A (TSA), a histone deacetylase inhibitor, induced the expression of PER1 protein in breast cancer cells (P< 0.05).Conclusion: PER1 functions as a tumor suppressor in the development and progression of breast cancer, and its expression silencing might be regulated by epigenetic modifications.Keywords: breast cancer, circadian clock gene, Period circadian regulator 1, PER1, tumor suppressor

Qiang Tan, Ming Chen, Jia Hao, Kun Wei Department of Cardiology, Qinhuangdao First Hospital, Hebei Medical University, Qinhuangdao, Hebei Province, People’s Republic of ChinaCorrespondence: Qiang TanDepartment of Cardiology, Qinhuangdao First Hospital, Hebei Medical University, No. 258 of Wenhua Road, Qinhuangdao, Hebei Province, 066000, People’s Republic of ChinaEmail qhdtanqiang@aliyun.comBackground and Objectives: Hyperinsulinemia plays a key role in the development of cardiovascular impairment in patients with metabolic syndrome. The aim of this study was to evaluate the influence of hyperinsulinemia on long-term clinical outcomes of percutaneous coronary intervention (PCI) in patients without diabetes mellitus who have acute myocardial syndrome (ACS).Methods: Between March 2016 and January 2019, we enrolled 468 patients with ACS and without diabetes mellitus who received primary PCI. Patients were divided into a low-insulin group (n = 157), medium-insulin group (n = 154), and high-insulin group (n = 157) according to tertiles of fasting insulin level. The primary endpoint was major adverse cardiac events (MACE; all-cause death, non-fatal myocardial infarction, target vessel revascularization [TVR]) at 24 months. The secondary endpoint was angina hospitalization.Results: Patients in the high-insulin group had an unfavorable prognosis, with a higher rate of MACE (34.39%) than the low-insulin group (22.29%) and medium-insulin group (23.37%) at 24 months (P < 0.05). This difference was mainly driven by the increase in TVR. The high-insulin group also had a higher rate of angina hospitalization than the low-insulin group. Cox proportional hazards regression showed that high-insulin level (hazard ratio [HR] 1.870, 95% confidence interval [CI] 1.202– 2.909), small-vessel lesion (HR 1.713, 95% CI 1.111– 2.642), bifurcation lesion (HR 3.394, 95% CI 2.033– 5.067), SYNTAX score (HR 1.084, 95% CI 1.039– 1.130), and stent length (HR 1.017, 95% CI 1.002– 1.032) increased the incidence of MACE in patients with ACS and without diabetes who underwent PCI.Conclusion: Hyperinsulinemia might be a valid predictor of clinical outcomes in patients with ACS undergoing PCI.Keywords: percutaneous coronary intervention, hyperinsulinemia, acute myocardial syndrome, major adverse cardiac events

Jinyong Hao,1,2 Xiaojun Huang1,2 1Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, People’s Republic of China; 2Gansu Provincial Digestive Endoscopy Engineering Research Center, Lanzhou, People’s Republic of ChinaCorrespondence: Jinyong Hao; Xiaojun HuangDepartment of Gastroenterology, Lanzhou University Second Hospital, No. 82 Linxia Road, Chengguan District, Lanzhou City, Gansu Province, 730030, People’s Republic of ChinaTel +86 18189556508Email haojinyong517@163.com; huangxj@lzu.edu.cnAbstract: Choledochoscopy technology has realized the direct observation of bile duct lesions, and can be loaded with a variety of special accessories to perform the corresponding diagnosis and treatment operations, and has become an important means for the diagnosis of unexplained bile duct stricture and treatment of refractory bile duct stones. With the further enhancement of the imaging quality and operability, the clinical application of choledochoscopy has gradually expanded to the precise positioning of cholangiocarcinoma before surgical resection, the drainage of the gallbladder through the nipple, the removal of the displaced bile duct stent and other fields. This paper briefly reviewed the historical evolution of choledochoscopy and reviewed the latest clinical advances of oral choledochoscopy in the diagnosis and treatment of biliary tract diseases.Keywords: oral choledochoscopy, SpyGlass, biliary stricture of unknown cause, refractory bile duct stones

Ying Ben,1,2,* Juan Hao,1,* Zhihong Zhang,1,2 Yunzhao Xiong,1 Cuijuan Zhang,1,2 Yi Chang,1,2 Fan Yang,1,2 Hui Li,1,2 Tianya Zhang,1 Xiangting Wang,1,2 Qingyou Xu1,2 1Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China; 2Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingyou XuHebei University of Chinese Medicine, No. 326 Xinshinan Road, Qiaoxi District, Shijiazhuang, Hebei Province, 050090, People’s Republic of ChinaTel +86 13832368865Fax +86 311 89926000Email qingyouxu@sohu.comPurpose: To investigate the effect of astragaloside IV (AS-IV) on mitochondrial-dependent apoptosis in the dorsal root ganglion of diabetic peripheral neuropathy (DPN) rats through the SIRT1/p53 pathway.Methods: Diabetic rat model was induced by high-carbohydrate/high-fat diet and intraperitoneal injection of STZ. Diabetic rats were divided into three groups (n =16 per group): DPN group, AS-IV group (60mg/kg/d) and α-lipoic acid (ALA) group (60mg/kg/d). Weight and blood glucose levels were monitored every 4 weeks for 12 weeks. DPN was evaluated using the Von Frey Filaments Test and nerve conduction velocity. The dorsal root ganglia of rats were isolated and the pathological changes of mitochondria were observed by electron microscopy. The activity of mitochondrial electron transport chain complex, mitochondrial membrane potential, malonaldehyde (MDA) and glutathione (GSH) levels were measured. Neural apoptosis was detected using the Terminal Deoxynucleotidyl Nick-End Labeling (TUNEL) assay kit. The cleaved caspase-3, major proteins in the SIRT1/p53 pathway, including SIRT1, acetyl p53, Drp1, BAX, and BCL-2, were detected using immunohistochemistry and Western blot. Gene expression of major proteins in the SIRT1/p53 pathway was also detected.Results: After 12 weeks of treatment, AS-IV and ALA did not significantly affect body weight or fasting glucose levels, but reduced mechanical abnormal pain in DPN and improved nerve conduction velocity. AS-IV and ALA increased the level of GSH and decreased the level of MDA. Both AS-IV and ALA can reduce mitochondrial damage, improve mitochondrial electron transport chain complex activity and mitochondrial membrane potential, and reduce the percentages of positive cells with DNA fragmentation and the expression of cleaved caspase-3 protein. AS-IV and ALA up-regulated the expression of SIRT1 and down-regulated the expression of acetyl-p53, Drp1 and the ratio of BAX to BCL-2. Changes in gene expression were similar.Conclusion: AS-IV can reduce the occurrence of mitochondrial-dependent apoptosis by regulating the SIRT1/p53 pathway. It has a similar therapeutic effect as ALA and is therefore a promising drug for the potential treatment of DPN.Keywords: astragaloside IV, diabetic peripheral neuropathy, dorsal root ganglion, mitochondria, apoptosis, SIRT1/p53 pathway

Xu Han,1,* Jialin Hao,2,* Suling Ding,3 En-Hua Wang,1 Liang Wang1 1Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, People’s Republic of China; 2Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, People’s Republic of China; 3Department of Pathology, Jinzhou Central Hospital, Jinzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang WangDepartment of Pathology, First Affiliated Hospital and College and Basic Medical Sciences, China Medical University, Shenyang, People’s Republic of ChinaTel/Fax +86 24 23261638Email cmuwangliang@qq.comAbstract: Bronchiolar adenoma (BA) is recognized as a neoplasm with benign clinical course. Histologically, BA is characterized by nodular proliferation of the bilayered bronchiolar-type epithelium, including multipartite epithelial cells and a continuous layer of basal cells. Recent reports have revealed the frequent presence of driver gene mutations in BA, suggesting its neoplastic nature. However, it is still debatable whether BA has malignant potential. Herein, we report the first case of BA harboring the same KRAS mutation with the adjacent invasive mucinous adenocarcinoma (IMA). Additionally, the loss of continuity of the basal cell layer in the junctional zone between BA and IMA indicated a malignant transformation from BA to IMA in this particular case.Keywords: bronchiolar adenoma, invasive mucinous adenocarcinoma, KRAS, transformation

Hao Su,1 Chen Chang,2 Jiajie Hao,2 Xin Xu,2 Mandula Bao,1 Shou Luo,1 Chuanduo Zhao,1 Qian Liu,1 Xishan Wang,1 Zhixiang Zhou,1 Haitao Zhou1 1Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Zhixiang Zhou; Haitao ZhouNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, People’s Republic of ChinaTel/Fax +861087787110Email zhouzhixiangdoctor@126.com; zhouhaitao01745@163.comPurpose: The molecular mechanism of perineural invasion (PNI) in stage II colorectal cancer (CRC) remains not to be defined clearly. This study aims to identify the genomic aberrations related to PNI in stage II CRC.Patients and Methods: Using array-based comparative genomic hybridization (array-CGH), primary tumor tissues and paracancerous normal tissues of stage II CRC with PNI and without PNI were analyzed. We identified genomic aberrations by using Genomic Workbench and MD-SeeGH and validated the aberrations of selected genes by real-time polymerase chain reaction (PCR). Gene ontology (GO) and pathway analysis were performed to determine the most likely biological effects of these genes.Results: The most frequent gains in stage II CRC were at 7q11.21-q11.22, 8p11.21, 8p12-p11.23, 8q11.1-q11.22, 13q12.13-q12.2, and 20q11.21-q11.23 and the most frequent losses were at 17p13.1-p12, 8p23.2, and 118q11.2-q23. Four high-level amplifications at 8p11.23-p11.22, 18q21.1, 19q11-q12, and 20q11.21-q13.32 and homozygous deletions at 20p12.1 were discovered in Stage II CRC. Gains at 7q11.21-q22.1, 16p11.2, 17q23.3-q25.3, 19p13.3-p12, and 20p13-p11.1, and losses at 11q11-q12.1, 11p15.5-p15.1, 18p11.21, and 18q21.1-q23 were more commonly found in patients with PNI by frequency plot comparison together with detailed genomic analysis. It is also observed that gains at 8q11.1-q24.3, 9q13-q34.3, and 13q12.3-q13.1, and losses at 8p23.3-p12, 17p13.3-p11.2, and 21q22.12 occurred more frequently in patients without PNI. Further validation showed that the expression of FLT1, FBXW7, FGFR1, SLC20A2 and SERPINI1 was significantly up-regulated in the NPNI group compared to the PNI group. GO and pathway analysis revealed some genes enriched in specific pathways.Conclusion: These involved genomic changes in the PNI of stage II CRC may be useful to reveal the mechanisms underlying PNI and provide candidate biomarkers.Keywords: array CGH, colorectal cancer, perineural invasion, biomarker

Fangyu Wang,1,* Junfang Hao,1,2,* Ning Li,3,* Guangxu Xing,1 Man Hu,1 Gaiping Zhang1,4 1Key Laboratory for Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, Henan 450002, People’s Republic of China; 2College of Biology and Food, Shangqiu Normal University, Shangqiu, Henan 476000, People’s Republic of China; 3College of Food Science and Technology, Henan Agricultural University, Zhengzhou, Henan 450000, People’s Republic of China; 4College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 450000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gaiping ZhangKey Laboratory for Animal Immunology, Henan Academy of Agricultural Sciences, 116# Huayuan Road, Zhengzhou, Henan Province 450002, People’s Republic of ChinaEmail zhanggaiping2003@163.comPurpose: The vaccine design has shifted from attenuated or inactivated whole pathogen vaccines to more pure and defined subunit vaccines. The purification of antigen proteins, especially the precise display of antigen regions, has become a key step affecting the effectiveness of subunit vaccines.Materials and Methods: This work presents the application of molecular docking for a peptide ligand designed for PCV2 Cap purification and assembly in one step. Based on the PCV2 Cap protein affinity peptide (L11-DYWWQSWE), the amino terminal of PCV2 Cap was covalently coupled with the polylactic acid–glycolic acid copolymer (PLGA) carboxyl terminal through the EDC/NHS method.Results: The PLGA had an average diameter of 106 nm. The average diameter increased to 122 nm after the PCV2 Cap protein conjugation, and the Zeta potential shifted from − 13.7 mV to − 9.6 mV, indicating that the PCV2 Cap protein stably binds to the PLGA. Compared with the free PCV2 Cap protein group, the neutralizing antibody titer was significantly increased on the 14th day after the PLGA-Cap immunization (P < 0.05). The neutralizing antibody level was extremely significant on the 28th day (P < 0.001). The CCK-8 analysis showed that PLGA-Cap had an obvious cytotoxic effect on RAW264.7 cells at the PLGA nanoparticle concentration up to 200 μg/mL but had no obvious cytotoxic effect on DC2.4 cells. Compared with the Cap protein group, the antigen-presenting cells had a stronger antigen uptake capacity and a higher fluorescence in the PLGA-Cap group. The immune effect showed that the level of the neutralizing antibody produced by this structure is much better than that of purified protein and helps improve the immune system response.Conclusion: This technology provides a potential new perspective for the rapid enrichment of the antigen protein with the affinity peptide ligand.Keywords: PCV2 Cap, peptide ligand, antigen display, protein assembly, nano vaccine, neutralizing antibody

Songming Li,* Junwen Hao,* Yun Hong, Junhao Mai, Weijun Huang Department of Thyroid and Breast Surgery, Guangzhou Panyu Central Hospital, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Songming Li Tel +86 13560013154Email LSMGZPCH@163.comBackground: Breast cancer (BC) is the most commonly diagnosed cancer in women. Tumor recurrence and metastasis are the key causes of death in BC patients. Long non-coding RNA (lncRNA) is closely associated with BC progression. lncRNA nuclear-enriched abundant transcript (NEAT)1 has been reported to regulate the proliferation and mobility of several types of cancer cells. However, how lncRNA NEAT1 affects the proliferation and invasion of BC cells is not known.Methods: Quantitative real time-polymerase chain reaction (qRT-PCR) was used to measure expression of lncRNA NEAT1 and microRNA (miR)-146b-5p in BC tissues and cell lines. Cell Counting Kit (CCK)-8, cell colony-formation, wound-healing, and Transwell™ assays were undertaken to determine the effects of lncRNA NEAT1 and miR-146b-5p on progression of BC cells. The interaction between lncRNA NEAT1 and miR-146b-5p was examined by luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and RNA-pulldown assays.Results: Expression of lncRNA NEAT1 was upregulated in BC tissues and cell lines. High expression of lncRNA NEAT1 predicted poor overall survival in BC patients. Silencing of expression of lncRNA NEAT1 inhibited epithelial–mesenchymal transition (EMT) and suppressed the proliferation, migration and invasion of BC cells. Ectopic expression of lncRNA NEAT1 induced EMT and promoted BC progression. Mechanistic investigations revealed that miR-146b-5p was a direct target of lncRNA NEAT1, and its expression was correlated negatively with expression of lncRNA NEAT1 in BC tissues.Conclusion: lncRNA NEAT1 could (i) serve as a novel prognostic marker for BC and (ii) be a potential therapeutic target for BC.Keywords: lncRNA NEAT1, miR-146b-5p, breast cancer, growth, metastasis

Xiufeng Zhang,1–3 Dongdong Han,1–3 Pengfei Pei,1–3 Jie Hao,1–3 Yixing Lu,1–3 Peng Wan,1–3 Xianfeng Peng,4 Weibiao Lv,5 Wenguang Xiong,1–3 Zhenling Zeng1–3 1National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, South China Agricultural University, Guangzhou 510642, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Veterinary Drugs Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, People’s Republic of China; 3National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou 510642, People’s Republic of China; 4Guangzhou Insighter Biotechnology Co., Ltd, Guangzhou 510642, People’s Republic of China; 5Department of Clinical Laboratory, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528000, People’s Republic of ChinaCorrespondence: Wenguang Xiong; Zhenling ZengSouth China Agricultural University, Wushan Road, Tianhe District, Guangzhou 510642, People’s Republic of ChinaTel +86 20-85281204Fax +86 20-85284896Email xiongwg@scau.edu.cn; zlzeng@scau.edu.cnBackground: Bacterial infections cause a serious public health crisis due to the emergence of resistance towards multiple conventional antibacterial drugs. In particular, multidrug-resistant (MDR) Enterococcus faecium which belongs to “ESKAPE” organisms is causing significant problems worldwide. Hence, there is an urgent need to find alternative therapies. Recently, substituted benzene guanidine compounds have been used as lead structures to discover new promising drugs in both synthetic and medicinal chemistry.Purpose: Here we investigated the antimicrobial activity of a new substituted benzene guanidine analog, isopropoxy benzene guanidine, against Enterococci.Material and methods: The isopropoxy benzene guanidine was synthesized by Guangzhou Insighter Biotechnology Co., Ltd and tested on both reference bacterial strain and 32 clinical MDR Enterococci strains. The in vitro antibacterial activity was evaluated by microdilution method and kill kinetic assays. The potential antibacterial mechanism was measured by fluorescence spectrometry using fluorescent membrane potential probe 3, 3-diethyloxacarbocyanine iodide (DiOC2 (3)).Results: Isopropoxy benzene guanidine exhibited potent bactericidal activity against both reference strain and MDR Enterococci isolates. The minimum inhibitory concentration (MIC) range for isopropoxy benzene guanidine was 1–4 μg/mL. Minimum bactericidal concentration (MBC) was about 2-8-fold of its MIC values. Time-kill studies showed that isopropoxy benzene guanidine provided superior bactericidal effect against reference and MDR strains within 12 hrs at 2×MIC. Furthermore, isopropoxy benzene guanidine could cause a large reduction in the magnitude of the generated membrane potential compared to that of the untreated cells.Conclusion: The present study highlights the potent bactericidal activity of isopropoxy benzene guanidine on Enterococci by disrupting the cell membrane potential. These findings demonstrate that isopropoxy benzene guanidine may be a good chemical lead for further medicinal chemistry and pharmaceutical development and could be used as a therapeutic agent for infectious diseases caused by MDR Enterococci.Keywords: isopropoxy benzene guanidine, MDR Enterococci, DiOC2, 3, cell membrane potential, bactericidal activity

Jing Hao,1 Rebecca Critchley-Thorne,2 David L Diehl,3 Susan R Snyder1 1Department of Epidemiology and Health Services Research, Geisinger, Danville, PA, USA; 2Research & Development, Cernostics Inc, Pittsburgh, PA, USA; 3Department of Gastroenterology, Geisinger, Danville, PA, USACorrespondence: Jing HaoDepartment of Epidemiology and Health Services Research, Geisinger, 100 N Academy Ave, MC44-00, Danville, PA 17822, USATel +1 570 214 2543Fax +1 570 214 9451Email jhao@geisinger.eduPurpose: This study evaluates the cost-effectiveness of a quantitative multi-biomarker assay (the Assay) that stratifies patients with Barrett’s Esophagus (BE) by risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) and can be used to guide clinical decisions, versus the current guidelines (standard of care [SOC]) for surveillance and treatment of BE.Patients and methods: Markov decision modeling and simulation were used to compare cost and quality-adjusted life-years (QALYs) from the perspective of a US health insurer with care delivered by an integrated health system. Model assumptions and disease progression probabilities were derived from the literature. Performance metrics for the Assay were from an independent clinical validation study. Cost of the Assay was based on reimbursement rates from multiple payers. Other costs were derived from Geisinger payment data.Results: Base-case model results for a 5-year period comparing the Assay-directed care to the SOC estimated an incremental cost-effectiveness ratio (ICER) of $52,483/QALY in 2012 US dollars. Assay-directed care increased the use of endoscopic treatments by 58.4%, which reduced the progression to HGD, EAC and reduced EAC-related deaths by 51.7%, 47.1%, and 37.6%, respectively, over the 5-year period. Sensitivity analysis indicated that the probability of the Assay being cost-effective compared to the SOC was 57.3% at the $100,000/QALY acceptability threshold.Conclusion: Given the model assumptions, the new Assay would be cost-effective after 5 years and improves patient outcomes due to improvement in the effectiveness of surveillance and treatment protocols resulting in fewer patients progressing to HGD and EAC and fewer EAC-related deaths.Keywords: Barrett’s esophagus, esophageal adenocarcinoma, risk prediction multi-biomarker assay, cost effectiveness

Li S, Wen D, Che S, et al. Onco Targets Ther. 2018;11:3215–3223. The Editor and Publisher of OncoTargets and Therapy wish to retract the published paper. Concerns were raised regarding the alleged manipulation and duplication of tumor images shown in Figure 6B. Specifically: Figure 6B, top row images for sh-NC, appear to be duplicated with images of the same tumors in Figure 2D from Liu et al, 2019 (https://doi.org/10.1016/j.biopha.2019.108862) and Figure 6B from Li et al, 2018 (https://doi.org/10.1016/j.biopha.2018.03.122). Similarly, Figure 6B, bottom row images for sh-LINC00152, also appear to be duplicated with images of the same tumors in Figure 2D from Liu et al, 2019 (https://doi.org/10.1016/j.biopha.2019.108862) and Figure 6B from Li et al, 2018 (https://doi.org/10.1016/j.biopha.2018.03.122). The authors responded to our queries but could not provide a satisfactory explanation for the alleged duplication or provide adequate raw data for their study. The findings of the study were deemed invalid and the Editor requested for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Caiyun Wang,1 Hongmei Xu,2 Jikui Deng,3 Hui Yu,4 Yiping Chen,5 Shifu Wang,6 Weichun Huang,7 Jianhua Hao,8 Chun Wang,9 Huiling Deng,10 Yinghu Chen11Infection Disease Department, The Children‘s Hospital of Zhejiang University School of Medicine, Hangzhou, 310052, People’s Republic of China; 2Infection Disease Department, Children‘s Hospital of Chongqing Medical University, Chongqing 400014, People’s Republic of China; 3Department of Infectious Diseases, Shenzhen Children‘s Hospital, Shenzhen 518038, People’s Republic of China; 4Department of Infectious Diseases, Children‘s Hospital of Fudan University, Shanghai 201102, People’s Republic of China; 5Infection Disease Department, Yuying Children‘s Hospital of Wenzhou Medical University, Wenzhou 325027, People’s Republic of China; 6Department of Children’s Medical Laboratory Diagnosis Center, Qilu Children‘s Hospital of Shandong University, Jinan, 250022, People’s Republic of China; 7Department of Clinical Laboratory, Shanghai Children‘s Medical Center of Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People’s Republic of China; 8Infection Disease Department, Kaifeng Children‘s Hospital, Kaifeng 475000, People’s Republic of China; 9Clinical Laboratory, Children’s Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, 200040, People’s Republic of China; 10Department of Infectious Diseases, Xi’an Children’s Hospital, Xi’an, 710003, People’s Republic of ChinaBackground: Prognosis of pneumococcal meningitis (PM) remains very poor, especially in less developed countries. Currently, few multi-centric studies on pediatric PM have been reported in mainland China.Objectives: This study aimed to explore the correlation of clinical and laboratory findings with complications and prognosis in pediatric PM.Methods: The pediatric PM patients were retrospectively recruited from ten pediatric tertiary hospitals across China between January 2013 and June 2018. Clinical, biochemical, and microbiological data and follow-up information were collected. Predictive factors for complications and prognostic factors for overall survival (OS) and sequelae-free survival (SFS) were analyzed.Results: A total of 132 pediatric PM patients were included. Seventy-one patients had complications, 25 patients died, and 39 patients had neurological sequelae. Multivariate logistic regression suggested that age less than 28 months (adjusted OR=2.654, 95%CI=1.067–6.600, P=0.036) and lower white blood cells in blood (aOR=3.169, 95%CI=1.395–7.202, P=0.006) were associated with high risk of complications. Multivariate Cox’s proportional hazard regression suggested that age less than 28 months (aHR=6.479, 95%CI=1.153–36.404, P=0.034), coma (aHR=9.808, 95%CI=2.802–34.323, P=0.000), and non-adjuvant steroid therapy (aHR=4.768 95%CI=1.946–11.678, P=0.001) were independent prognostic factors for poor OS; coma (aHR=5.841, 95%CI=2.652–12.864, P=0.000), septic shock on admission (aHR=2.949, 95%CI=1.049–8.290, P=0.040), and lower glucose level in cerebrospinal fluid (CSF) (aHR=2.523, 95%CI=1.336–4.765, P=0.004) were independent prognostic factors for poor SFS.Conclusion: Age, coma, and adjuvant steroid therapy were independent factors for OS, while coma, septic shock on admission, and lower glucose level in CSF were independent factors for SFS in pediatric PM patients. These factors might be used to identify PM patients with poor prognosis and guide individual treatment.Keywords: pneumococcal meningitis, clinical findings, complication, prognosis, pediatric

Daniel D Maeng, Jove Graham, Michael Bogart, Jing Hao, Eric A Wright Department of Epidemiology and Health Services Research, Geisinger, Danville, PA, USA Purpose: Pharmacist-led medication therapy disease management (MTDM) has shown improvement in clinical outcomes in patients with certain chronic diseases. However, only limited data demonstrating the impact on health care utilization and cost of care are available. This study seeks to evaluate the impact of a pharmacist-led MTDM program on clinical surrogate outcomes, care utilization, and cost of care among patients with diabetes mellitus. Methods: A retrospective cohort study was conducted by utilizing electronic health records and insurance claims data. Patients were identified between February 2011 and December 2014. Data were collected from Geisinger, a large integrated health care system located in Pennsylvania and southern New Jersey. A total of 5,500 patients with diabetes mellitus were identified; 2,750 were enrolled in MTDM and were 1-to-1 propensity score-matched to a comparison cohort not enrolled in a pharmacist-led MTDM program. Results: There were no differences between groups in composite HbA1c, blood pressure, or low-density lipoprotein cholesterol goal attainment at 12 months (12% vs 12%, P=0.53). HbA1c goal was reached more frequently among patients without MTDM compared to those at 12 months (57% vs 51%, P

Yinan Jiang,1 Meiling Zhang,2 Tangxi Guo,1 Chaogang Yang,1 Chunxiao Zhang,1 Jinjin Hao2 1Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; 2Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Background: MicroRNAs could target multiple genes by regulating the translation or degradation of mRNAs, and are involved in functions such as signal transduction pathways affecting the physiological functions of normal or tumor cells. Methods: In this study, the expressions of miRNA-21-5p in gastric cancer tissues and SGC-7901 cells were analyzed, and the effects of miRNA-21-5p on cell proliferation, migration, invasion, and apoptosis and the expressions of target proteins SMADs in SGC-7901 cells were evaluated. Inflammatory factors interleukin 1β and tumor necrosis factor α in siRNA-transfected SGC-7901 cells were determined by enzyme-linked immunosorbent assay. Results: MiRNA-21-5p was consistently upregulated in gastric cancer tissues and SGC-7901 cells compared to normal tissues or cells. The knockdown of miRNA-21-5p with antisense oligonucleotides suppressed cell proliferation, migration, and invasion as well as inflammatory response, and promoted cell apoptosis and SMAD7 expression. Conclusion: These results indicate SMAD7 may mediate the oncogenic properties of miRNA-21-5p in gastric cancer, and miRNA-21-5p would be a promising strategy for the treatment of gastric cancer. Keywords: miRNA-21-5p, gastric cancer, SMAD7, SGC-7901, migration, invasion

Songhe Li,1 Dacheng Wen,2 Songtian Che,3 Zhihua Cui,1 Yabin Sun,1 Hua Ren,1 Jilong Hao1 1Department of Ophthalmology, The First Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, People’s Republic of China Background: A growing body of evidence supports the involvement of long noncoding RNA 00152 (LINC00152) in the progression and metastasis of multiple cancers. However, the exact roles of LINC00152 in the progression of human retinoblastoma (RB) remain unknown. We explored the expression and biological function of human RB.Materials and methods: The expression level of LINC00152 in RB tissues and cells was analyzed using quantitative real-time PCR. The function of LINC00152 was determined using a series of in vitro assays. In vivo, a nude mouse model was established to analyze the function of LINC00152. Gene and protein expressions were detected using quantitative real-time PCR and Western blot assays, respectively.Results: The expression of LINC00152 mRNA was upregulated in RB tissues and cell lines. Knockdown of LINC00152 significantly inhibited cell proliferation, colony formation, migration, and invasion and promoted cell apoptosis and caspase-3 and caspase-8 activities in vitro, as well as suppressing tumorigenesis in vivo. We identified several genes related to proliferation, apoptosis, and invasion including Ki-67, Bcl-2, and MMP-9 that were transcriptionally inactivated by LINC00152.Conclusion: Taken together, these data implicate LINC00152 as a therapeutic target in RB. Keywords: retinoblastoma, LINC00152, proliferation, invasion

Quanwu Sun,1,* Chuan Zhou,2,* Ruofei Ma,3 Qianhong Guo,4 Haiyun Huang,1 Jie Hao,1 Hong Liu,1 Rong Shi,1 Bo Liu1 1Department of Breast Surgery, The People’s Hospital of Gansu Province, Lanzhou City, Gansu, China; 2Department of Urology/Institute of Urology, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, China; 3Department of Abdominal Surgery, Gansu Tumor Hospital, Lanzhou City, Gansu, China; 4Department of Oncological Surgery, The First People’s Hospital of Tianshui City, Tianshui City, Gansu, China *These authors contributed equally to this work Abstract: Integrin-beta 1 (ITGB1) is aberrantly overexpressed or downregulated in solid cancers; however, its prognostic value remains controversial. Therefore, we conducted a meta-analysis to explore whether ITGB1 expression is correlated with overall survival (OS) and the clinicopathological characteristics of patients with solid cancers. We systematically searched the PubMed, Embase, and Web of Science databases for eligible studies published up to June 1, 2017. In total, 22 studies involving 3,666 patients were included. A sensitivity analysis was performed to assess the validity and reliability of the pooled OS. Among the 22 studies, 7 focused on lung cancer, 3 focused on colorectal cancer, 6 focused on breast cancer, 3 involved melanoma, and 3 involved pancreatic cancer. The pooled results showed that high ITGB1 expression was significantly associated with worse OS in lung cancer (pooled hazard ratio [HR]=1.78, 95% CI: 1.19–2.65, p

Xiao-Yu Cheng,1,2 Zou Liu,1,2 Li Shang,1 Hong-Qing Cai,1 Yu Zhang,1,2 Yan Cai,1,2 Xin Xu,1,2 Jia-Jie Hao,1,2 Ming-Rong Wang1,2 1State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2Center for Cancer Precision Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China Abstract: Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, with a low 5-year overall survival rate. In previous studies, we and others have found that 9p21.3 was the most frequently deleted region in ESCC. The MTAP gene, which is located close to CDKN2A/B in 9p21.3, encodes methylthioadenosine phosphorylase. This enzyme plays an important role during the process of adenosine transfer. In the present study, we found that MTAP is deleted at the genomic level in 19.1% (64/341) of primary ESCC tumors, and decreased mRNA and protein expression were present in 31.1% (28/90) and 33.3% (6/18) of ESCCs, respectively. Further statistical analysis showed a positive correlation between deletion and decreased mRNA expression of MTAP in the ESCC tissues tested (coefficient: 0.826; P=1.17×10-23). Knockdown of MTAP expression using small interfering RNA-mediated silencing promoted the invasion and migration of ESCC cells. Also, overexpression of MATP using pcDNA3.1-MTAP plasmid decreased the cell invasion and migration. At the molecular level, MTAP knockdown downregulated E-cadherin and p-GSK3β but upregulated Slug expression. Our results indicated that MTAP deletion results in the decreased expression in ESCCs and that it plays a role in promoting the mobility and inducing the epithelial-to-mesenchymal transition of ESCC cells via the GSK3β/Slug/E-cadherin axis. The data suggest that MTAP might function as a tumor suppressor gene in ESCC. Keywords: ESCC, MTAP, deletion, invasion, migration

Sarra Setrerrahmane,1 Jian Yu,1 Jingchao Hao,1,2 Heng Zheng,3 Hanmei Xu1,3 1The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, Jiangsu, 2College of Pharmacy & the Provincial Key Laboratory of Natural Drug and Pharmacology, Kunming, Yunnan, 3State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China Background: Developing innovative drugs with potent efficacy, specificity, and high safety remains an ongoing task in antitumor therapy development. In the last few years, peptide drugs have become attractive agents in cancer therapy. HM-3, mainly with antiangiogenic effect, and AP25, with an additional antiproliferative effect, are two peptides designed in our laboratory targeting αvβ3 and α5β1 integrins, respectively. The low molecular weight of the two peptides renders their recombinant expression very difficult, and the complicated structure of AP25 makes its chemical synthesis restricted, which presents a big challenge for its development.Methods: Bifunctional peptides designed by the ligation of HM-3 and AP25, using linkers with different flexibility, were prepared using recombinant DNA technology in Escherichia coli. The fusion peptides were expressed in a modified auto-induction medium based on a mixture of glucose, glycerol, and lactose as carbon substrates and NH4+ as nitrogen source without any amino acid or other elements. Subsequently, the antiangiogenic, antiproliferative, and cell adhesion assays were conducted to evaluate the bioactivity of the two fusion peptides.Results: The peptides were successfully expressed in a soluble form without any induction, which allows the culture to reach higher cell density before protein expression occurs. Human umbilical vein endothelial cell migration assay and chick embryo chorioallantoic membrane assay showed, at low doses, a significantly increased antiangiogenic effect (>75%) of the purified products compared with the single molecules. Meanwhile, MTT assay confirmed their enhanced antitumor activity against gastric cancer cell line MGC-803; however, no significant effect was observed on hepatoma HepG2 cells and no cytotoxicity on normal human lens epithelial cell SRA01/04 and human epithelial esophageal cells.Conclusion: Bifunctional molecules with antiangiogenic and antiproliferative effects were obtained by using this technique, which presents an alternative for small peptide production, instead of the conventional chemical method. The increased molecular weight facilitates the peptide expression with a simultaneous improvement in their stability and biological activity. Keywords: innovative drugs, bifunctional peptides, linkers, auto-induction, antiangiogenic, antitumor

Nan Zhang,1 Ronghui Wang,2 Junnian Hao,1 Yang Yang,1 Hongmi Zou,3 Zhigang Wang1 1Chongqing Key Laboratory of Ultrasound Molecular Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, 2Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 3Department of Ophthalmology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Abstract: High-intensity focused ultrasound (HIFU) is a promising and noninvasive treatment for solid tumors, which has been explored for potential clinical applications. However, the clinical applications of HIFU for large and deep tumors such as hepatocellular carcinoma (HCC) are severely limited by unsatisfactory imaging guidance, long therapeutic times, and damage to normal tissue around the tumor due to the high power applied. In this study, we developed doxorubicin/perfluorohexane-encapsulated hollow mesoporous Prussian blue nanoparticles (HMPBs-DOX/PFH) as theranostic agents, which can effectively guide HIFU therapy and enhance its therapeutic effects in combination with chemotherapy, by decreasing the cavitation threshold. We investigated the effects of this agent on ultrasound and magnetic resonance imaging in vitro and in vivo. In addition, we showed a highly efficient HIFU therapeutic effect against HCC tumors, as well as controlled drug release, owing to the phase-transitional performance of the PFH. We therefore conclude that HMPB-DOX/PFH is a safe and efficient nanoplatform, which holds significant promise for cancer theranostics against deep tumors in clinical settings. Keywords: high-intensity focused ultrasound, HIFU, hollow mesoporous Prussian blue nanoplatforms, hepatocellular carcinoma, dual-modality imaging, synergistic chemo-/thermotherapy, theranostics