Search

Dongle Liu,1– 3 Honglei Li,1– 3 Simeng Zheng,1– 3 Jiajun Sun,1– 3 Huiran Bai,1– 3 Xiaoming Wu1– 3 1Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, People’s Republic of China; 2State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Qingdao, People’s Republic of China; 3School of Ophthalmology, Shandong First Medical University, Qingdao, People’s Republic of ChinaCorrespondence: Xiaoming Wu, Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, 5 Yanerdao Road, Qingdao, 266000, People’s Republic of China, Email wuxiaominglmm@126.comObjective: To evaluate and compare the clinical outcomes of rotationally asymmetric multifocal intraocular lenses (IOLs) in a mix-and-match approach or bilateral implantation.Methods: In this prospective study, patients were split into two groups based on the types of IOLs implanted. The mix group received mix-and-match implantation of a LENTIS Mplus LS-313 +1.50D IOL in the dominant eye and a LENTIS Mplus LS-313 +3.0D IOL in the fellow eye. The bilateral group received bilateral implantation of LENTIS Mplus LS-313 +3.00D IOLs. A three-month follow-up was performed after the surgery. Binocular visual acuity at various distances, subjective refraction and defocus curves were assessed. Subjective questionnaires included the overall satisfaction, a self-assessment of visual quality, spectacle independence, and presence of photic phenomena were completed.Results: The study was completed by 52 patients in total (25 mix-and-match, 27 bilateral). The mean binocular uncorrected intermediate visual acuity in the mix group and the bilateral group were 0.10 ± 0.12 logMAR and 0.23 ± 0.14 logMAR, respectively, demonstrating a significant difference (P = 0.005). The mix group performed better in intermediate vision (range: − 1.00 to − 2.00 D) than the bilateral group (all P< 0.05), according to binocular defocus curves. About 92.0% of patients in the mix group did not need spectacles for intermediate distance vision compared to 59.26% in the bilateral group (P = 0.0001).Conclusion: The mix-and-match implantation of the +1.50D and +3.00D rotationally asymmetric multifocal IOLs provided good binocular visual outcomes and resulted in better intermediate vision than bilateral implantation of +3.00D IOLs.Keywords: multifocal intraocular lenses, mix-and-match, visual outcomes

Meng Zhang,1,2 Qi Yuan,1 Peiwen Wang,1 Fan Zhang,1 Dan Wu,1 He Bai,1 Jieting Liu,1 Haifeng Liu,1 Xiaohuan Yuan1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2The First Hospital of Qiqihar, Qiqihar, People’s Republic of ChinaCorrespondence: Xiaohuan Yuan, College of Life Science, Mudanjiang Medical University, No. 3 Tongxiang Road, Mudanjiang, 157011, People’s Republic of China, Tel/Fax +86-453-6984401, Email yuanxiaohuan@mdjmu.edu.cnPurpose: Nanovesicles (NVs) derived from bone mesenchymal stem cells (BMSCs) as drug delivery systems are considered an effective therapeutic strategy for diabetes. However, its mechanism of action remains unclear. Here, we evaluated the efficacy and molecular mechanism of BMSC-derived NVs carrying the curcumin analog H8 (H8-BMSCs-NVs) on hepatic glucose and lipid metabolism in type 2 diabetes (T2D).Subjects and Methods: Mouse BMSCs were isolated by collagenase digestion and H8-BMSCs-NVs were prepared by microvesicle extrusion. The effects of H8-BMSCs-NVs on hepatic glucose and lipid metabolism were observed in a T2D mouse model and a HepG2 cell insulin resistance model. To evaluate changes in potential signaling pathways, the PI3K/AKT/AMPK signaling pathway and expression levels of G6P and PEPCK were assessed by Western blotting.Results: H8-BMSCs-NVs effectively improved lipid accumulation in liver tissues and restored liver dysfunction in T2D mice. Meanwhile, H8-BMSCs-NVs effectively inhibited intracellular lipid accumulation in the insulin resistance models of HepG2 cells. Mechanistic studies showed that H8-BMSCs-NVs activated the PI3K/AKT/AMPK signaling pathway and decreased the expression levels of G6P and PEPCK.Conclusion: These findings demonstrate that H8-BMSCs-NVs improved hepatic glucose and lipid metabolism in T2D mice by activating the PI3K/AKT/AMPK signaling pathway, which provides novel evidence suggesting the potential of H8-BMSCs-NVs in the clinically treatment of T2D patients.Keywords: bone mesenchymal stem cell, nanovesicles, curcumin analogue H8, type 2 diabetes

Wei Zheng, Jianhua Liu, Haixia Bai, Xin Xu, Lina Wu, Xiaosong Qin Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Liaoning Clinical Research Center for Laboratory Medicine, Shengyang, People’s Republic of ChinaCorrespondence: Xiaosong Qin, Email qinxs@sj-hospital.orgBackground: Gordonia terrae is an opportunistic pathogen that rarely causes clinical infections. Here, we first report a case of spontaneous bacterial peritonitis in patients with hepatitis C cirrhosis caused by Gordonia terrea.Case Presentation: A 71-year-old male patient was diagnosed with spontaneous bacteria peritonitis secondary to hepatitis C cirrhosis. The result of bacterial culture in ascites was positive, and the pathogenic bacteria was preliminarily identified as the Gordonia genus by matrix-assisted laser desorption ionization–time of flight mass spectrometry. After 16S rRNA sequencing analysis, it was determined to be the Gordonia terrea. Symptoms relieved after treatment with ceftazidime.Conclusion: This case indicates that the clinical infections caused by Gordonia terrea should be brought to the forefront. Accurate and rapid bacterial identification results are highly beneficial to the diagnosis and therapeutic regime.Keywords: spontaneous bacterial peritonitis, rare pathogen, Gordonia terrae, identification

Hua Bai,1 Na He,2 Yan Zhang,3 Aqsa Ahmad,3 Xing-Xing Yang,3 Yan Ma,3 Li-Jun Liang1 1Department of Pediatrics, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2PKUFH-NINGXIA Women Children’s Hospital, Yinchuan, 750001, People’s Republic of China; 3The First Clinical Medical College of Ningxia Medical University General Hospital, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Li-Jun Liang, Department of Pediatrics, General Hospital of Ningxia Medical University, 804 Shengli South Street, Yinchuan, Ningxia, 750004, People’s Republic of China, Tel +86 137 0959 6527, Email lianglijunlj@126.comObjective: In this study, we aimed to evaluate the current status of the quality of life (QOL) of pediatric patients and plasma glucose concentration regulation in children with type 1 diabetes (T1DM) in the Ningxia Hui autonomous region.Methods: The study involved children with T1DM admitted to the General Hospital of Ningxia Medical University between October 2011 and October 2021. The children and their parents completed general information and quality of life (QOL) questionnaires. The regulation of plasma glucose concentration was assessed based on HbA1c levels, and plasma glucose and QOL-influencing components were investigated.Results: Among the 136 pediatric patients diagnosed with T1DM, the mean glycated hemoglobin (HbA1c) level was recorded at 8.7% (7.2%, 10.5%). A breakdown of the patient cohort revealed that 44 patients (32.4%) demonstrated good regulation of plasma glucose, 33 patients (24.3%) exhibited acceptable glycemic control, and 59 patients (43.3%) displayed poor regulation of plasma glucose. The control of plasma glucose in pediatric patients diagnosed with T1DM was affected by the duration of the disease, the patient’s age, the frequency of daily plasma glucose measurements, the use of CGM, diabetic ketoacidosis (DKA), and the education level of the mother. The control of plasma glucose, dietary management, DKA, the ability to learn, and health education are interfering factors of quality of life in children diagnosed with T1DM. Effective control of plasma glucose may ensure the QOL in children with T1DM, and DKA was the risk factor for QOL.Conclusion: In Ningxia, the regulation of plasma glucose in pediatric and adolescent patients with T1DM remains suboptimal, leading to poor QOL. There is a pressing need to enhance glucose regulation and QOL through comprehensive strategies, which include reinforced dietary management, rigorous monitoring of plasma glucose levels, and heightened health education levels.Keywords: current status of regulation of plasma glucose concentration, influencing factors, QOL, type 1 diabetes

Binbin Liu,1,&ast; Pan Su,1,&ast; Peilei Hu,1,&ast; Mi Yan,1 Wenbin Li,1 Songlin Yi,1 Zhenhua Chen,1 Xiaoping Zhang,1 Jingwei Guo,1 Xiaojie Wan,1 Jue Wang,1 Daofang Gong,1 Hua Bai,1 Kanglin Wan,2 Haican Liu,2 Guilian Li,2 Yunhong Tan1 1Clinical Laboratory, Hunan Chest Hospital, Changsha, People’s Republic of China; 2National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunhong Tan, Clinical Laboratory, Hunan Chest Hospital, Changsha, People’s Republic of China, Tel +86-13874947876, Email Tanyunhong@163.com Guilian Li, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China, Tel +86-18519886112, Email liguilian@icdc.cnBackground: China is a country with a burden of high rates of both TB and multidrug-resistant TB (MDR-TB). However, published data on pyrazinamide (PZA) resistance are still limited in Hunan province, China. This study investigated the prevalence, transmission, and genetic diversity of PZA resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Hunan province.Methods: Drug susceptibility testing (DST) with the Bactec MGIT 960 PZA kit and pyrazinamidase (PZase) testing were conducted on all 298 MDR clinical isolates. Moreover, 24-locus MIRU-VNTR and DNA sequencing of pncA, rpsA, and panD genes were conducted on 180 PZA-resistant (PZA-R) isolates.Results: The prevalence of PZA resistance among MDR-TB strains reached 60.4%. Newly diagnosed PZA-R TB patients and clustered isolates with identical pncA, rpsA, and panD mutations showed that transmission of PZA-R isolates played a significant role in the formation of PZA-R TB. Ninety-eight mutation patterns were observed in the pncA among 180 PZA-R isolates, and seventy-one (72.4%) were point mutations. Twenty-four of these mutations are new, including 2 base substitutions (V93G and T153S) and 22 nucleotide deletions or insertions. The W119C was found in PZA-S isolates, on the other hand, F94L and V155A mutations were found in both PZA resistant and susceptible isolates with positive PZase activity, indicating that they were not associated with PZA resistance. This is not entirely in line with the WHO catalogue. Ten novel rpsA mutations were found in 10 PZA-R isolates, which all combined with mutations in pncA. Thus, it is unpredictable whether these mutations in rpsA can impact PZA resistance. No panD mutation was found in all PZA-R isolates.Conclusion: DNA sequencing of pncA and PZase activity testing have great potential in predicting PZA resistance.Keywords: tuberculosis, pyrazinamide, transmission, pncA mutations, rpsA mutations, panD mutations, China

Hua Bai, Wen-Hui Wang, Fan-Fan Zhou, Dan Yang, Rui-Jun Li Department of Oncology, People’s Hospital of Zhengzhou, Zhengzhou, People’s Republic of ChinaCorrespondence: Rui-Jun Li, Department of Oncology, People’s Hospital of Zhengzhou, No. 33, Huanghe Road, Jin-Shui District, Zhengzhou, 450053, People’s Republic of China, Tel +86 13838508075, Email liruijunzy@163.comObjective: Therapeutic regimens are relatively scarce among patients with treatment-refractory metastatic colorectal cancer (CRC). This study aimed to determine the feasibility and tolerability of anlotinib plus PD-1 blockades in patients with treatment-refractory metastatic CRC retrospectively.Methods: A total of 68 patients with previously treated metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in this study retrospectively. Demographic and clinical characteristics of the patients, therapeutic outcomes and safety profile during administration were collected and briefly analyzed. All subjects were followed up regularly. Therapeutic outcomes, including drug response and prognosis, were presented, and a safety profile was depicted to illustrate the adverse reactions.Results: A total of 68 patients with treatment-refractory metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in the final analysis. Best therapeutic response during treatment indicated that partial response was observed in 11 patients, stable disease was noted in 41 patients, and progressive disease was found in 16 patients, producing an objective response rate of 16.2% (95% CI: 8.4%– 27.1%) and a disease control rate of 76.5% (95% CI: 64.6%– 85.9%). Prognostic analysis suggested that the median progression-free survival (PFS) of the 68 patients was 5.3 months (95% CI: 3.01– 7.59), and the median overall survival (OS) was 12.5 months (95% CI: 9.40– 15.60). Of the 11 patients who responded, the median duration of response was 6.7 months (95% CI: 2.89– 10.53). Safety profile during treatment showed that patients experienced adverse reactions regardless of grade, and grade ≥ 3 adverse reactions were found in 61 patients (89.7%) and 41 patients (60.3%), respectively. Common adverse reactions were hypertension, myelosuppression (including leukopenia, neutropenia, thrombocytopenia, and anemia), fatigue, and hand-foot syndrome.Conclusion: Anlotinib plus PD-1 blockades demonstrated encouraging efficacy and acceptable safety profile in patients with treatment-refractory metastatic CRC preliminarily in clinical practice. This conclusion should be confirmed in prospective clinical trials.Keywords: colorectal cancer, anlotinib, PD-1 blockades, efficacy, safety

Menggege Liu,1,2 Qing Zhang,1,3 Juan Liu,1 Huiling Bai,1 Ping Yang,1 Xinhua Ye,1,3 Xiaoqing Yuan1,3 1Department of Endocrinology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 2Second Clinical College, Dalian Medical University, Dalian, People’s Republic of China; 3Changzhou Medical Center, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of ChinaCorrespondence: Xiaoqing Yuan; Xinhua Ye, Email adiposeyy@126.com; Endocrine1314@163.comObjective: To analyze the relationship between leg skeletal muscle mass index (LSMI) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) and the ability of LSMI to predict NAFLD.Methods: Two hundred patients with T2DM and NAFLD treated at Changzhou Second People’s Hospital Affiliated with Nanjing Medical University and the National Metabolic Management Center from June 2022 to June 2023 were divided into four LSMI quartiles. The clinical information from the four patient groups was compared, and the relationship between type 2 diabetes and LSMI and NAFLD was examined. We used receiver operating characteristic curves to determine how well the LSMI predicts NAFLD in T2DM.Results: The lowest quartile (Q1) had a higher prevalence of NAFLD than group Q4 (P < 0.05). LSMI was negatively associated with body mass index, LS, CAP, and other markers (P < 0.05). Receiver operating characteristic curve analysis LSMI predicted NAFLD with an ideal critical value of 0.64 and an area under the curve of 70.9%. The combined predictive value of the LSMI and the appendicular skeletal muscle mass index was more significant.Conclusion: Reduced LSMI is associated with NAFLD.Keywords: non-alcoholic fatty liver disease, type 2 diabetes mellitus, LSMI, ASMI

Shuya Chen,1 Yunhan Deng,2 Yan Zhai,2 Yang Zhan,3 Xue Li,4 Jiandong Wang,1 Huimin Bai2 1Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pathology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 4Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jiandong Wang, Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Qihelou Street, Dongcheng District, Beijing, 100006, People’s Republic of China, Tel +0086-13910566755, Email wangjiandongxy@ccmu.edu.cn Huimin Bai, Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8, North Road of Workers Stadium, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +0086-01085231765, Email bhmdoctor@sina.comPurpose: To reveal the clinical status and construct a predictive prognostic model for patients with uterine leiomyosarcoma (uLMS) at International Federation of Gynecology and Obstetrics (FIGO) stage I.Patients and Methods: The medical records of patients with stage I uLMS during the study period were retrospectively reviewed. Multiple imputation, Martingale residuals and restricted cubic spline were used for data processing. Univariate and multivariate analyses were used to determine independent prognostic factors. The Schoenfeld individual test was used to verify the proportional hazards (PH) assumption. The predictive ability of the nomogram was validated internally.Results: Ultimately, 102 patients were included. The median age at diagnosis was 51 years old. During the medium follow-up time of 68 months, 55 (53.9%) patients developed recurrence. The median recurrence interval was 32 months. The most common metastatic site was the lung (27 cases). Eventually, 38 (37.3%) patients died of uLMS. The 3-year and 5-year overall survival rates were 66.0% and 52.0%, respectively. Age at diagnosis > 49 years, larger tumor size, MI> 10/10HPF, presence of LVSI and Ki-67 labeling index (LI) > 25% (P=0.0467, 0.0077, 0.0475, 0.0294, and 0.0427, respectively) were independent prognostic factors. The PH assumption remained inviolate. The concordance index was 0.847, the area under the time-dependent receiver operating characteristic curve surpassed 0.7, and the calibration curve showed gratifying consistency.Conclusion: Age at diagnosis, tumor size, MI, LVSI, and Ki-67 LI were identified as independent prognostic factors for stage I uLMS. This prognostic nomogram would provide personalized assessment with superior predictive performance.Keywords: uterine leiomyosarcoma, prognosis, nomogram, risk stratification

Min Sun,1,2 Lei Gao,1 Hongmei Bai,1 Weiwei Hu,1 Xiaofang Zhang,1 Jin Xiao,1 Xiangliang Deng,1 Hongmei Tao,1 Ping Ge,2 Yuhong Qin,1,&ast; Dongying Zhang1,&ast; 1Department of Cardiovascular Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Health Management Center, The First Branch of the Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongying Zhang; Yuhong Qin, Tel +86-23-13608398395 ; +86-23-13068357151, Email zhangdongying@cqmu.edu.cn; 798213639@qq.comPurpose: To investigate the association of visceral fat with arterial stiffness of heart failure patients with preserved ejection fraction (HFpEF) and to evaluate the extent to which this association is mediated by blood pressure (BP).Patients and Methods: This cross-sectional descriptive study (clinicaltrials.gov identifier: NCT04535726) recruited 94 patients with HFpEF totally from October to December 2020. The obesity-related measurements included visceral fat area (VFA), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist–hip ratio (WC/HC), abdominal circumference (AC), body fat mass and fat percentage. Brachial-ankle pulse wave velocity (baPWV) was used to estimate the degree of arterial stiffness. Mediation analysis was performed to reveal whether the effect of visceral fat area on arterial stiffness can be mediated by BP in patients with HFpEF and the extent to which this association was mediated by BP.Results: About 93.6% of HFpEF patients were accompanied with abdominal obesity. Patients in baPWV ≥ 1800cm/s group were older, with a higher incidence of type 2 diabetes mellitus (T2DM), hypertension and abdominal obesity. VFA, systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) were correlated with baPWV in total group. Adjusted for age ≥ 75 years old, gender, smoking, T2DM, calcium channel blocker and statins, the mediation effect of systolic SBP and PP on the VFA-baPWV association were 53.3% (indirect effect was 2.28, 95% CI 0.62– 4.73) and 48.4% (indirect effect was 2.07, 95% CI 0.51– 4.38), respectively. DBP failed to mediate the association between VFA and baPWV (indirect effect was 0.50, 95% CI − 0.41– 2.14).Conclusion: The association of visceral fat with baPWV in HFpEF patients may be partly accounted for SBP or PP. Elevated SBP and PP might be important potential targets for preventing arterial stiffness in HFpEF patients.Keywords: mediation analysis, blood pressure, visceral fat area, brachial-ankle pulse wave velocity, HFpEF

The efficient generation, manipulation and detection of magnetic skyrmions are important for the development of future spintronic devices. One approach is to use electric-current-induced spin torques. Recently, thermally induced skyrmion motion has also been observed, but wider experimental evidence and its capabilities remain limited. Here we report the thermal generation, manipulation and thermoelectric detection of nanoscale skyrmions in microstructured metallic multilayers integrated with on-chip heaters. The local application of heat can facilitate a domain morphological transition and the formation of skyrmions at the device edge, where a low energy barrier exists. We observe the unidirectional diffusion of skyrmions from hot regions to cold regions, which is due to the interplay among the repulsive forces between skyrmions, thermal spin–orbit torques, entropic forces and magnonic spin torques. The thermally generated skyrmions can also be electrically detected via the Nernst voltage.

Jianxia Ma,1,&ast; Jianqin Sun,2,&ast; Huijing Bai,2 Houlian Ma,1 Ke Wang,1 Jun Wang,1 Xiaofeng Yu,1 Yiru Pan,3 Jianfeng Yao1 1Department of Gastroenterology, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Clinical Nutrition Center, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Clinical Laboratory, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfeng Yao, Department of Gastroenterology, Huadong Hospital Affiliated to Fudan University, No. 221. Road West Yanan, Shanghai, 200040, People’s Republic of China, Tel +862162483180, Email yjf1966@126.comPurpose: This study was to explore the influence of flax seeds on the gut microbiota of elderly patients with functional constipation.Patients and Methods: Sixty elderly patients (68.68± 8.73 years) with functional constipation were recruited between January 2018 and March 2018. They received oral flax seeds (50 g/d) for one month. Bowel habits and adverse events were recorded before and after treatment. Fresh stool was collected before and after treatment and the amplification product of 16S rRNA V5 region was sequenced using the next-generation sequencing technique on the Ion Torrent PGM platform. The gut microbiota were analyzed before and after flax seeds treatment in the same subject.Results: Flax-seed treatment significantly increased the frequency of defecation and decreased abdominal distension in elderly patients with chronic constipation. The majority of gut bacteria belonged to the phyla of Firmicutes, Bacteroidetes, and Proteobacteria, accounting for 98.71%. After flax seeds treatment, the diversity of bacterial clusters significantly increased with increases of Roseburia_hominis, Pseudomonas_azotoformans, uncultured_Clostridiales_bacterium, Blautia_obeum, Ruminococcus_sp._16442, Pyramidobacter_piscolens, Acinetobacter_lwoffii, Prevotella_melaninogenica. The abundance of Blautia in patients with chronic constipation was significantly lower than healthy controls, while Blautia_obeum increased significantly after flax seed treatment. Blautia_obeum might be the predominant genus accounting for the therapeutic effect of flax seeds.Conclusion: Flax seeds may improve the defecation in elderly patients with chronic constipation and change intestinal microecological structure. Thus, flax seeds may serve as an effective diet supplement in the management of chronic constipation.Keywords: constipation, flax seeds, high-throughput sequencing, gut microbiota

Zheng S, Zhang M, Bai H, et al. Int J Nanomedicine. 2019;14:9513–9524. The authors have advised due to an error at the time of figure assembly, the image of Spleen at 1 day in Figure 8B on page 9522 is incorrect. The correct Figure 8 is shown below. Figure 8 In vivo toxicity test of Mn-MoS2 QDs: (A(a–l)) Mouse serum biochemistry analysis and blood routine analysis before (0d, control) and after injection of Mn-MoS2 QDs for 1, 7, 21d. (B) Histological images of the heart, lungs, liver, spleen and kidneys of mice 1, 7 and 21 days post-intravenous injection of Mn-MoS2 QDs and in control mice. The organs were sectioned and stained with hematoxylin and eosin (H&E) and observed under a light microscope, scale bar = 100 μm. The authors apologize for this error and advise it does not affect the results of the paper.

Hai Zhao,1,&ast; Yaqiong Huang,1,&ast; Hao Wang,2 Juan Zhao,1 Shanshan Tian,1 Haixia Bai,1 Mufang Guo,1 Caiping Dong,1 Yongliang Shi,1 Xia Li,1 Chengjun Zhu,1 Tao Feng,1 Xia Ma,3 Zhifei Hou1,4 1Department of Pulmonary and Critical Care Medicine, Sinopharm Tongmei General Hospital, Datong, People’s Republic of China; 2School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Respiratory and Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhifei Hou; Xia Ma, Tel +86 18811189252 ; +86 15103510398, Email houzhifei1898@126.com; maxialn007@sina.comPurpose: CWP is an untreatable but preventable fibrotic lung disease caused by the chronic inhalation of coal dust. Genetic factors such as polymorphisms play an important role in the development of CWP. The present study investigated the association between the polymorphisms of SMAD4 and NLRP3 and CWP risk in a Chinese Han population.Patients and Methods: SMAD4 rs10502913 and NLRP3rs1539019 polymorphisms were examined in 292 CWP subjects and 315 coal dust-exposed controls. The genotypes were analyzed using direct sequencing. The allele and genotype proportion between the cases and controls were compared using the chi-square test.Results: The AG and GG genotypes of SMAD4 rs10502913 were not associated with altered CWP risk compared with AA genotype (adjusted OR = 1.535 and 1.426, 95% CI = 0.785– 3.000 and 0.732– 2.781, p = 0.210 and 0.297, respectively). Also, the NLRP3 rs1539019 heterozygous and homozygous variants CA and CC genotypes were not associated with the risk of CWP compared with the AA genotype (adjusted OR = 0.985 and 1.127, 95% CI = 0.652– 1.489 and 0.713– 1.782, p = 0.944 and 0.608, respectively). In addition, there was no interaction between SMAD4 rs10502913 and NLRP3 rs1539019 genotypes and smoking status on CWP risk in the stratified analyses.Conclusion: In this present study, SMAD4 rs10502913 and NLRP3 rs1539019 genotypes were not associated with altered CWP risk in the Chinese Han population. Large sample sizes and multicenter studies are needed to elucidate these results in the future.Keywords: CWP, polymorphisms, SMAD4 rs10502913, NLRP3 rs1539019

Lingli Han,1 Ji Zhang,2 Jingxuan Yang,1 Xiaoyu Yang,1 Hua Bai1 1The Third Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Zhengzhou Maternal and Child Health Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Hua Bai, The Third Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China, Tel +86 371 66903017, Email sfyhlb3726@zzu.edu.cnPurpose: Postpartum depression is related to many factors, which affect the health of mothers and infants. The purpose of this study is to test the mediated effect of self-efficacy in the relationship between vulnerable personality and postpartum depression.Patients and Methods: A cross-sectional survey was conducted with pregnant women aged ≥ 20 years from February to April 2021 in Zhengzhou, China. We recruited 587 pregnant women, and 429 pieces of data were available. The demographic characteristics questionnaire, General Self efficacy Scale (GSES) and Vulnerable Personality Style Questionnaire (VPSQ) were distributed in the prenatal survey. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen postpartum depression symptoms at one month through WeChat and telephone follow-up. A mediated model was constructed to explain the relationship of variables and test the mediated effect of self-efficacy.Results: The valid questionnaires were 429 (effective response rate: 90.7%). The vulnerable personality and low self-efficacy were related to postpartum depression (all P< 0.01). The self-efficacy of pregnant women was inversely associated with vulnerable personality (β= − 0.415) and postpartum depression (β= − 0.216). The vulnerable personality and self-efficacy can explain 29.0% of the variation in postpartum depression. It was confirmed that a partial mediating effect of self-efficacy accounted for 18.0% (0.090/0.501) of the total effect.Conclusion: Maternal self-efficacy partly mediates the relationship between vulnerable personality traits and postpartum depression. The study implies the importance of targeted interventions to improve self-efficacy for women with vulnerable personality traits to reduce the risk of postpartum depression.Keywords: postpartum depression, vulnerable personality, self-efficacy, mediated effect

Huiran Bai,1,2 Honglei Li,1,2 Simeng Zheng,1,2 Lihong Sun,1,2 Xiaoming Wu1,2 1Qingdao Eye Hospital of Shandong First Medical University, Qingdao, People’s Republic of China; 2State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, People’s Republic of ChinaCorrespondence: Xiaoming WuDepartment of Ophthalmology, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, People’s Republic of ChinaTel +86532-87610668Email wuxiaominglmm@126.comPurpose: To investigate the incidence of Nd:YAG capsulotomy after implantation of two types of multifocal intraocular lenses (MIOLs).Methods: This retrospective analysis included patients who had undergone cataract extraction and implanted diffractive MIOL (Acri. LISA tri 839M) or asymmetric refractive MIOL (SBL-3) from May 2016 to September 2018. They were followed up for at least 3 years. During the follow-up period, the relevant data of patients were kept by special person in the hospital. The rates of Nd:YAG capsulotomy and the Kaplan–Meier survival curve were used to analyze the two groups.Results: The Asymmetric Refractive MIOL group was comprised of 98 patients (121 eyes), while the Diffractive MIOL group was comprised of 99 patients (120 eyes). There were no significant differences in age, sex, or IOL power between the two groups. The Nd:YAG rate of the asymmetric refractive MIOL group and the diffractive MIOL group was 3.3% and 7.5% respectively (P = 0.15) in the first year, 14.88% and 22.5% respectively (P = 0.129) in the second year, and 21.49% and 34.17% respectively (P = 0.028) in the third year. In the first 7 months of follow-up, the two groups showed the same performance in the Nd:YAG rate. After that, there was a difference between the two groups, and the difference gradually increased. Until the 27th month of follow-up, the difference was significant (P < 0.05). What is more, there were significant differences in survival (without Nd:YAG capsulotomy)/failure (with Nd:YAG capsulotomy) functions (P = 0.0035).Conclusion: The incidence of Nd:YAG laser capsulotomy in patients with diffractive MIOLs was higher than that in patients with asymmetric refractive MIOLs.Keywords: Nd:YAG capsulotomy rates, asymmetric refractive MIOL, diffractive MIOL, posterior capsular opacification

Zuli Fu,1,2 Qian Xu,1 Chiyuan Zhang,1,3 Hui Bai,1 Xuliang Chen,1 Yanfeng Zhang,1 Wanjun Luo,1 Guoqiang Lin1 1Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Guoqiang LinDepartment of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of ChinaTel/Fax +86-731-84327097Email lgq186snoopy@126.comPurpose: Post-operative delirium (POD) is a common complication after aortic surgery with poor outcomes. Blood pressure may play a role in the occurrence of POD. The study aimed to identify whether admission systolic blood pressure (SBP) level in the intensive care unit (ICU) is correlated with POD in acute Stanford type A aortic dissection (AAAD) patients undergoing aortic surgery.Patients and Methods: We conducted a single-center retrospective cohort study enrolling consecutive 205 patients with acute type A aortic dissection undergoing aortic surgery. Patients were divided into 3 groups: low, normal, and high SBP level group. Outcomes of interest were POD, 30-day mortality and other complications including acute kidney injury, cardiac complications, spinal cord ischemia, stroke, and pneumonia. Confusion Assessment Method for Intensive Care Unit (CAM-ICU) method was used to assess POD. Univariate and multivariate logistic regression, Cox regression, and subgroup analysis were performed to uncover the association between SBP and POD.Results: The mean age of these patients was 51± 16 years old. Thirty-six patients (17.6%) developed POD. Patients with high admission SBP were more likely to develop POD (P < 0.01). Univariate analysis showed that high admission SBP was associated with a higher risk of POD among AAAD patients (OR, 3.514; 95% CI, 1.478– 8.537, P < 0.01). Multivariate logistic regression model confirmed that high SBP was an independent predictor of POD. Subgroup analysis indicated that patients with anemia and high admission SBP were at higher risk of POD.Conclusion: High admission SBP was positively associated with the incidence of POD in AAAD patients who underwent surgical repair in ICU.Keywords: acute Stanford type A aortic dissection, intensive care unit, major surgery, post-operative delirium, systolic blood pressure

Honglei Li,1,2 Dongle Liu,1,2 Han Gao,3 Jiajun Sun,1,2 Huiran Bai,1,2 Xiaoming Wu1,2 1Qingdao Eye Hospital of Shandong First Medical University, Qingdao, People’s Republic of China; 2State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, People’s Republic of China; 3Department of Ophthalmology, Qingdao Central Hospital, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Xiaoming WuQingdao Eye Hospital of Shandong First Medical University, 5 Yanerdao Road, Qingdao, 26600, People’s Republic of ChinaEmail wuxiaominglmm@126.comPurpose: This study compared the clinical outcomes after cataract surgery with implantation of refractive rotationally asymmetric bifocal intraocular lens (IOL) (LS-313 MF30) and apodized diffractive bifocal IOL (ReSTOR SN6AD1).Methods: This was a prospective, non-randomized, controlled study, where patients diagnosed with age-related cataracts were selected for phacoemulsification combined with bilateral IOL implantation. Based on the type of IOL voluntarily implanted, the patients were divided into two groups, ie, refractive and diffractive groups. In total, 30 cases (60 eyes) were in a refractive group, while 30 cases (60 eyes) were in diffractive group. Three months after surgery, we examined the uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), defocus curve, objective visual quality, and subjective questionnaire.Results: Three months after surgery, the UIVA of the refractive group (0.18 ± 0.08) logMAR was better than that of the diffractive group (0.29 ± 0.16) logMAR (P < 0.05). No significant difference in UDVA and UNVA was noted between the two groups. For a 4mm pupil diameter, the intraocular and total eye aberration, higher-order aberration (HOA), coma, spherical aberration, and trefoil in the refractive group were significantly higher than those in diffractive group (P < 0.05). The intraocular modulation transfer function (MTF), intraocular strehl ratio (SR), total eye MTF, and total eye SR in the refractive group were lower than those in diffractive group (P < 0.05). No significant difference in glare incidence, spectacle independence rate, and patient satisfaction was observed between the two groups (P > 0.05). The halos incidence in the refractive group was lower than the diffractive group (P < 0.05).Conclusion: Both bifocal IOLs obtained satisfactory UDVA and UNVA, with higher patient satisfaction. Unlike the apodized diffractive bifocal IOL, the refractive rotationally asymmetric bifocal IOL yielded slightly better UIVA, lower halos incidence, whereas the apodized diffractive bifocal IOL showed a better objective visual quality.Keywords: refractive rotationally asymmetric, apodized diffractive, intraocular lens, visual quality

Liao Tan,1,2 Qian Xu,3 Chan Li,2 Xuliang Chen,3 Hui Bai3 1Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Hui BaiDepartment of Cardiovascular Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410013, People’s Republic of ChinaEmail 2211200403@qq.comObjective: Serum bicarbonate (HCO3−) level is strongly related to multiple cardiovascular complications. Currently, there is no study evaluating the prognostic ability of serum HCO3− level in intensive care unit (ICU) patients with acute aortic dissection (AAD). Hence, this study was to assess the relationship between admission serum HCO3− level and clinical outcomes in patients with AAD.Design, Settings and Participants: Clinical data were extracted from the MIMIC-III database. Cox proportional hazards models and Kaplan–Meier (KM) survival curve were used to evaluate the association between serum HCO3− levels and short- and long-term mortality in ICU patients with AAD. The subgroup analysis and the receiver operating characteristic (ROC) curve analysis and further KM survival curve based on best cut-off value were applied to assessment of the performance of HCO3− in predicting the mortality in each period (30 days, 90 days, 1 year and 5 years).Main Results: Firstly, 336 eligible patients were trisected to low-HCO3− level group (< 22 mmol/L), mid-HCO3− level group (22– 24 mmol/L) and high-HCO3− level group (> 24 mmol/L). Then, in multivariate analysis, the serum HCO3− of low levels (< 22 mmol/L) was a significant risk predictor of all-cause mortality in 30 days, 90 days, 1 year and 5 years. Subgroup analyses indicated that there is no interaction in most strata. Finally, areas under ROC curve ranged from 0.60 to 0.69.Conclusion: The low HCO3− serum level measured at ICU admission significantly predicts short-term and long-term mortality in AAD patients.Keywords: serum bicarbonate, intensive care unit, acute aortic dissection, all-cause mortality

Shunjie Bai,1,&ast; Jing Xie,2,&ast; Huili Bai,3 Tian Tian,4 Tao Zou,5,6 Jian-Jun Chen7 1Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Endocrinology, the Fourth People’s Hospital of Chongqing, Chongqing University Central Hospital, Chongqing, People’s Republic of China; 3The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Neurology, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 5Department of Psychiatry, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 6Shanghai Key Laboratory of Forensic Medicine, Academy of Forensic Science, Shanghai, People’s Republic of China; 7Institute of Life Sciences, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian-Jun ChenInstitute of Life Sciences, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaEmail chenjianjun@cqmu.edu.cnTao ZouDepartment of Psychiatry, The Affiliated Hospital of Guizhou Medical University, Yunyan District, Guiyang, Guizhou Province, 550004, People’s Republic of ChinaEmail zoutaozou@tom.comBackground: Although many works have been conducted to explore the biomarkers for diagnosing major depressive disorder (MDD), the widely accepted biomarkers are still not identified. Thus, the combined application of serum metabolomics and fecal microbial communities was used to identify gut microbiota-derived inflammation-related serum metabolites as potential biomarkers for MDD.Methods: MDD patients and healthy controls (HCs) were included in this study. Both serum samples and fecal samples were collected. The liquid chromatography mass spectrometry (LC-MS) was used to detect the metabolites in serum samples, and the 16S rRNA gene sequencing was used to analyze the gut microbiota compositions in fecal samples.Results: Totally, 60 MDD patients and 60 HCs were recruited. The 24 differential serum metabolites were identified, and 10 of these were inflammation-related metabolites. Three significantly affected inflammation-related pathways were identified using differential metabolites. The 17 differential genera were identified, and 14 of these genera belonged to phyla Firmicutes. Four significantly affected inflammation-related pathways were identified using differential genera. Five inflammation-related metabolites (LysoPC(16:0), deoxycholic acid, docosahexaenoic acid, taurocholic acid and LysoPC(20:0)) were identified as potential biomarkers. These potential biomarkers had significant correlations with genera belonged to phyla Firmicutes. The panel consisting of these biomarkers could effectively distinguish MDD patients from HCs with an area under the curve (AUC) of 0.95 in training set and 0.92 in testing set.Conclusion: These findings suggested that the disturbance of phyla Firmicutes might be involved in the onset of depression by regulating host’s inflammatory response, and these potential biomarkers could be useful for future investigating the objective methods for diagnosing MDD.Keywords: major depressive disorder, gut microbiota, biomarkers, inflammation, metabolite

Junlong Guo,1,2 Lulu Yang,1,2 Yan Xu,1,2 Chenxi Zhang,1,2 Xian Luo,1,2 Shuai Liu,1– 3 Lihua Yao,4 Hanping Bai,4 Xiaofen Zong,4 Jihui Zhang,5 Zhongchun Liu,4 Bin Zhang1,2 1Department of Psychiatry, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Mental Health Center, Guangdong Provincial People’s Hospital, Guangzhou, People’s Republic of China; 3Department of Psychiatry, The Third People’s Hospital of Qinghai Province, Xining, People’s Republic of China; 4Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 5Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Bin ZhangDepartment of Psychiatry, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People’s Republic of ChinaTel +86-20-62786731Email zhang73bin@hotmail.comZhongchun LiuDepartment of Psychiatry, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, People’s Republic of ChinaEmail zcliu6@whu.edu.cnIntroduction: The prevalence rate and related factors of insomnia remained unknown after the COVID-19 epidemic had been under control. Therefore, we conducted this survey to investigate the prevalence rate and related factors of insomnia symptoms in the Chinese general public after the COVID-19 had been initially control.Methods: An online survey was conducted among Chinese citizens through the JD Health APP. The questionnaire was used for collecting demographic data and self-designed questions related to the COVID-19 outbreak. Insomnia Severity Index, Patient Health Questionnaire-9, Somatic Symptom Scale-8 and Impact of Events Scale-Revised were used for measuring psychological symptoms. To examine the associations of sociodemographic and psychological factors with insomnia symptoms, a binary logistic regression was used.Results: In total, there were 14,894 eligible participants, and 4601 (30.9%) participants were found to have insomnia symptoms. The regression model revealed that a higher risk of insomnia symptoms was associated with being over the age of 40 years, having history of psychiatric disorders, smoking, having infected friends or colleagues, having depressive or somatic symptoms, experiencing psychological distress and feeling estranged from family members. Meanwhile a lower risk of insomnia symptoms was associated with being female, having closer family relationships, not feeling alienated from others and being satisfied with the available information.Conclusion: In our study, 30.9% of the participants in the general public reported insomnia symptoms after the COVID-19 epidemic had been initially controlled. When providing precise interventions for insomnia, extra attention should be paid to the individuals who are male, elderly and smokers, and those with psychiatric disorder history, with infected friends or colleagues, with psychological symptoms and with poor social support.Keywords: insomnia symptoms, prevalence, COVID-19, under control, general public, China

Han Bai,1 Jianjun Yu,2 Shidong Jia,2 Xiaoran Liu,1 Xu Liang,1 Huiping Li1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People’s Republic of China; 2Huidu Shanghai Medical Sciences, Shanghai, 201499, People’s Republic of ChinaCorrespondence: Xu Liang; Huiping LiKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, People’s Republic of ChinaTel/Fax +86-10-88196739Email liangxu15@outlook.com; huipingli2012@hotmail.comPurpose: The status of TP53 mutations was measured in cell-free DNA from patients with metastatic breast cancer (MBC) to investigate disease characteristics and the prognostic role of different locations of the TP53 mutation site.Patients and Methods: Blood samples were taken from a total of 187 patients diagnosed with MBC who were treated at the Department of Breast Oncology, Peking University Cancer Hospital between January 2013 and March 2020. Next-generation sequencing was used to investigate the TP53 mutation spectra of circulating free DNA in these blood samples.Results: Among the 187 MBC patients, TP53-mutated patients had a significantly shorter median disease-free survival (DFS) and overall survival (OS) compared with TP53 wild-type patients (P=0.001 and P=0.006, respectively). Additionally, in hormone receptor positive/HER2 negative (HR+/HER2-) and triple negative (TNBC) cohorts, TP53-mutated patients had a significantly shorter median DFS than TP53 wild-type patients (P=0.038 and P=0.023, respectively). The 79 patients with TP53 mutations carried 87 somatic TP53 mutations, of which most (77.0%) mapped to the DNA-binding domain (DBD) of the protein encoded by TP53 exons 5– 8. In patients with TP53 mutations, those occurring in the non-DBD had a significantly shorter median DFS and OS than TP53 wild type (P< 0.001 and P=0.001, respectively). Additionally, patients with non-missense mutations in the DBD had a significantly shorter median DFS and OS than TP53 wild-type patients (P=0.001 and P< 0.001, respectively). TP53-mutated patients had a significantly shorter DFS than TP53 wild-type patients in the adjuvant endocrine therapy sensitive group (P=0.008), but differences in the endocrine therapy resistant group were not significant.Conclusion: TP53-mutated MBC patients had a significantly worse outcome than TP53 wild-type patients especially those in HR+/HER2– and TNBC cohorts. Of TP53-mutated patients, those with non-missense mutations in the DBD had worse breast cancer-related survival. TP53 mutations were also associated with endocrine resistance.Keywords: advanced breast cancer, TP53 mutation, NGS, adjuvant endocrine therapy, DNA-binding domain

Shunjie Bai,1 Liang Fang,2,3 Jing Xie,4 Huili Bai,1 Wei Wang,5 Jian-jun Chen6 1Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Cerebral Vascular Disease Research, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Endocrinology and Nephrology, The Fourth People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 5Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 6Institute of Life Sciences, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Jian-jun Chen, Email chenjianjun@cqmu.edu.cnBackground: Major depressive disorder (MDD) and suicide are two major health problems, but there are still no objective methods to diagnose MDD or suicidal ideation (SI). This study was conducted to identify potential biomarkers for diagnosing MDD patients with SI.Methods: First-episode drug-naïve MDD patients with SI and demographics-matched healthy controls (HCs) were recruited. First-episode drug-naïve MDD patients without SI were also included. The serum lipids, C-reactive protein (CRP), transferring (TRSF), homocysteine (HCY) and alpha 1-antitrypsin (AAT) in serum were detected. The univariate and multivariate statistical analyses were used to identify and validate the potential biomarkers.Results: The 86 HCs, 53 MDD patients with SI and 20 MDD patients without SI were included in this study. Four potential biomarkers were identified: AAT, TRSF, high-density lipoprotein cholesterol (HDLC), and apolipoprotein A1 (APOA1). After one month treatment, the levels of AAT and APOA1 were significantly improved. The panel consisting of these potential biomarkers had an excellent diagnostic performance, yielding an area under the ROC curve (AUC) of 0.994 and 0.990 in the training and testing set, respectively. Moreover, this panel could effectively distinguish MDD patients with SI from MDD patients without SI (AUC=0.928).Conclusion: These results showed that these potential biomarkers could facilitate the development of an objective method for diagnosing MDD patients with SI, and the decreased AAT levels in MDD patients might lead to the appearance of SI by resulting in the elevated inflammation.Keywords: major depressive disorder, suicidal ideation, biomarkers

Wei Jin,1,* Jian-Chun Duan,2,* Zhi-Jie Wang,2 Lin Lin,2 Hua Bai,2 Jie Wang,2 Li Feng1 1Department of Chinese Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 2State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie WangState Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, People’s Republic of ChinaTel +86 139-1070-4669Email zlhuxi@163.comLi FengDepartment of Chinese Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, People’s Republic of ChinaTel +86 186-1814-7576Email fengli663@126.comAbstract: Immunotherapy provided with checkpoint inhibitors such as the programmed cell death-1 (PD-1) receptor or its ligand-1 (PD-L1) protein has been shown to be effective for treating several types of cancer, and was recently approved for use in treating malignant melanoma, advanced non-small cell lung cancer (NSCLC), urothelial carcinoma, head and neck squamous cell carcinoma, liver cancer, and additional forms of cancer. However, there is little evidence concerning its effectiveness in treating thymic squamous cell carcinoma (TSCC). Here, we report two cases of refractory TSCC that were treated with PD-1 single/combination therapy in a clinical setting. The patients exhibited variable responses to therapy without any serious adverse events. In summary, our findings show that immunotherapy provided with an immuno-checkpoint inhibitor in combination with chemotherapy/anti-angiogenesis therapy can improve the treatment response of patients with refractory TSCC. Anti-PD-1 single/combination therapy may be used as a strategy for treating advanced refractory TC.Keywords: thymic carcinoma, anti-PD-1, single/combination therapy

Ruili Jiao,1,2,* Shipeng Sun,3,* Xiaoqiong Gao,1 Ran Cui,1 Guangming Cao,1 Huali Wei,4 Shuzhen Wang,1 Zhenyu Zhang,1 Huimin Bai1 1Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 2Department of Obstetrics and Gynecology, Maternal and Child Health Hospital, Beijing, People’s Republic of China; 3Clinical Laboratories, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Department of Obstetrics and Gynecology, Emergency General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huimin Bai; Zhenyu Zhang Email bhmdoctor@sina.com; zhenyuzhang@ccmu.edu.cnObjective: This study tried to evaluate whether 8% polyethylene glycol (PEG) 6000 precipitation combined with differential ultracentrifugation (PPDU) was an efficient and practical method for the enrichment and purification of extracellular vesicles (EVs) derived from the culture supernatant of human ovarian cancer cell line A2780 and from body fluids of patients with high-grade serous carcinoma (HGSC).Methods: PPDU was used to enrich and purify the EVs derived from body fluids of patients with HSGC and cell culture supernatant of subclones of human ovarian cancer cell line A2780 with high/low invasive capacity (named as A-H/A-L, respectively). Transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA) were used to identificate the EVs size and distribution. Western blots (WB) were used to detect the expression of CD9, CD63, Alix and Calnexin. The high-purity EVs derived from the cell culture supernatant of A-H/A-L were detected by the protein profile. Expression of integrins (ITGs) αV, β 1 and β 3 in the EVs derived from body fluids of HGSC patients was also evaluated.Results: The diameter of EVs was about 30– 260 nm observed under the TEM. Under the NTA identification, the peak size of EVs was ranged from 70 to 159nm. EVs derived from different specimens did not significantly differ in mean size and peak size. Presence of CD9, CD63 and Alix and absence of Calnexin were confirmed in the EVs. The protein concentrations of EVs’ sample extracted from A-H/A-L cell culture supernatant were 0.36μg/μL and 0.20μg/μL, respectively. The total amount of protein obtained from 300ul EVs was 108.02ug and 61.44ug, respectively. Totally, 2397 peptides and 952 proteins were identified by isobaric tags for relative and absolute quantitation (ITRAQ). The expression of ITGαV, β 1, and β 3 in the EVs from plasma and ascites of HGSC patients was significantly higher than the control group (plasma: all P< 0.0001; ascites: P=0.036, 0.001 and 0.004, respectively). The expression level of ITGαV and β 1 in EVs of HGSC’s ascites was significantly higher than that in plasma (P= 0.004, 0.001, respectively). The expression of ITGβ 3 was also slightly elevated in EVs-derived HGSC patients’ ascites (P=0.492).Conclusion: PPDU was an efficient and practical method to enrich EVs from body fluids and cell culture supernatant. The characteristic expression of ITGαV, β 1 and β 3 in ascites and plasma EVs of patients with HGSC provided useful information on the development of EVs in HGSC.Keywords: EVs, PEG6000 precipitation, HGSC, body fluids, cell culture supernatant

Linjun Hu,1,* Qinxin Zhao,2,* Hongsong Bai,1 Chengming Xie,1 Xingli Shan,1 Dehu Lu,1 Yonghai Chen,1 Dongdong Han,1 Zejun Xiao,2 Jun Tian,2 Dong Wang,2 Xingang Bi,2 Nianzeng Xing2 1Department of Urology, Cancer Hospital of HuanXing Chaoyang District Beijing, Beijing, People’s Republic of China; 2Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nianzeng XingDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan South Li, Beijing, Chaoyang 100021, People’s Republic of ChinaEmail xingnianzeng@hotmail.comPurpose: The aim of this study was to evaluate the efficacy and safety of hormonal and synchronous docetaxel plus prednisone (DocP) in metastatic hormone-sensitive prostate cancer (mHSPC).Methods: One hundred fifty-one cases with high-burden mHSPC diagnosed at 1 single center from January 2014 to August 2018 were analyzed retrospectively. Among them, 85 cases received androgen-deprivation therapy (ADT) within 3 months, along with 6 cycles of docetaxel + prednisone (treatment group), whereas 66 received ADT alone (control group). The primary end point was the median overall survival (OS), while the secondary outcomes included prostate-specific antigen (PSA) progression-free survival (PFS), radiographic PFS, and the proportion of PSA falling to 0.2 ng/mL.Results: A total of 151 patients were included and followed up for a median of 34 months in this study. The median OS time in the treatment group was unavailable, but it was remarkably longer than that of the control group (P< 0.001). In addition, the PFS of PSA in the treatment group and control group was 17.9 months and 9.2 months, respectively (P< 0.001). Meanwhile, the radiographic PFS was 43 months in the treatment group and 19.8 months in the control group, respectively (P< 0.001). The proportions of PSA falling to 0.2 ng/mL were 53.7% and 23.3%, respectively (P< 0.001). However, there was no significant difference in the incidence of ≥ 3 toxic side effects between these 2 groups (P=0. 21).Conclusion: ADT combined with 6 cycles of docetaxel + prednisone chemotherapy benefits patients diagnosed with high-burden mHSPC in terms of the OS, PFS of PSA and radiographic, and the ratio of PSA falling to 0.2 ng/mL.Keywords: androgen-deprivation therapy; ADT, docetaxel, high-burden, metastatic hormone-sensitive, prostate cancer;PCa

Huili Bai,1,* Rong Wang,1,2,* Wei Cheng,1 Yifan Shen,1 Haijun Li,2 Wei Xia,1 Zhenglin Ding,3,* Yuhong Zhang1,* 1The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Laboratory Medicine, Guangyuan Central Hospital, Guangyuan, Sichuan, People’s Republic of China; 3Department of Laboratory Medicine, The People’s Hospital of Nanchuan, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuhong Zhang; Zhenglin Ding Email zhangyuhong0730@126.com; 782829997@qq.comBackground: Microsatellite instability (MSI) is one of the most important molecular characteristics of colorectal cancer (CRC), which mainly results from defective DNA mismatch repair (MMR). This study was performed to investigate the concordance between deficient MMR and MSI testing, and to evaluate the association of these two results with clinicopathological characteristics in Chinese CRC patients.Methods: A total of 738 CRC patients were included. Tumor tissues and paired peripheral blood specimens were obtained. Screening for MMR was investigated using immunohistochemical (IHC) technique, and multiple polymerase chain reaction-capillary electrophoresis (PCR-CE) method was performed to detect the MSI status. All clinicopathological data, immunohistochemistry and microsatellite instability analyses were then statistically analyzed.Results: Of the 738 (17.75%) CRC patients, 131 expressed as deficient mismatch repair (dMMR) status, and postmeiotic segregation increased 2 (PMS2) deficiency was the most frequent deficiency among these four MMR proteins. MSI-high (MSI-H) status occurred in 74 of the 738 (10.03%) CRC patients, 55 of whom showed instability at all six mononucleotides repeat markers. dMMR was significantly associated with MSI-H and moderate concordance was observed between IHC and PCR-CE in evaluating deficient MMR/MSI through Kappa test. Statistically, dMMR was significantly associated with younger age, right-sided colon and poor differentiation. MSI-H was associated with younger age, right-sided colon, poor differentiation, mucinous type and tumor, node, metastasis (TNM) stage II.Conclusion: A moderate concordance between deficient MMR and MSI testing indicates that both IHC and PCR-CE methods should be routinely tested to provide reliable data for clinical treatment decisions.Keywords: deficient mismatch repair, microsatellite instability, clinicopathological features, colorectal cancer

Na Wang,1,* Xinxin Wang,2,* Wenya Li,2,* Huajun Ye,3 Hongzhao Bai,2 Jiansheng Wu,3 Mengjun Chen3 1Health Care Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325002, People’s Republic of China; 2Wenzhou Medical University, Wenzhou, Zhejiang 325002, People’s Republic of China; 3Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325002, People’s Republic of China *These authors contributed equally to this workCorrespondence: Mengjun Chen; Jiansheng WuDepartment of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Nan Bai Xiang Street, Ouhai District, Wenzhou, Zhejiang 325002, People’s Republic of ChinaTel +86-577-55579521Fax +86-577-55579792Email wenzhoucmj@163.com; lunina123@126.comObjective: The aim of this study was to determine the role of contrast-enhanced computed tomography (CE-CT) parameters in predicting the expression status of HER2 in gastric adenocarcinoma (GAC) patients before radical gastrectomy.Materials and Methods: A total of 460 GAC patients who underwent non-contrast CT (NC-CT) and CE-CT examinations before radical resection were enrolled in this retrospective study. The radiologists reviewed their CT scans and recorded parameters, including CT attenuate value (CAV) and corrected CAV (cCAV). The pathologist identified the postoperative HER2 expression status, and HER2 expression status was evaluated by immunohistochemical staining (IHC). The association between CE-CT parameters and HER2 expression status was analyzed.Results: Among the 460 patients, 84 patients had HER2 over-expression status, at a prevalence of 18.3%. The CAVs were significantly different between the 2 different HER2 expression groups in the non-contrast and arterial phases (non-contrast phase: p = 0.005; arterial phase: p < 0.001). Besides, there was a significant difference in the cCAVs between the 2 groups in the arterial phase (arterial phase: p = 0.003). Univariate and multivariate logistic regression analyses identified that the maximum diameter of tumor, differentiation degree, CAV in non-contrast, arterial, and portal phases, and cCAV in the arterial phase were predictive factors of HER2 expression status.Conclusion: Our analyses showed that the CE-CT parameters were significantly different between different HER2 expression groups. CE-CT parameters could serve as simple, objective predictive factors of HER2 expression status of GAC patients.Keywords: gastric adenocarcinoma, contrast-enhanced-CT, human epidermal growth factor receptor 2

Wenxiang Bai,1,2,* Honghua Wang,1,* Hua Bai1,3 1Comprehensive Cancer Center, Xiangshui People’s Hospital, Xiangshui 224600, People’s Republic of China; 2Department of Respiratory Medicine, Xiangshui People’s Hospital, Xiangshui, 224600, People’s Republic of China; 3Department of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua BaiComprehensive Cancer Center, Xiangshui People’s Hospital, Xiangshui 224600, People’s Republic of ChinaEmail baihua92@126.comObjective: Systemic amyloid light chain (AL) amyloidosis is a rare plasma cell disease. However, the regulatory mechanisms of AL amyloidosis have not been thoroughly uncovered, identification of candidate genes and therapeutic agents for this disease is crucial to provide novel insights into exploring the regulatory mechanisms underlying AL amyloidosis.Methods: The gene expression profile of GSE73040, including 9 specimens from AL amyloidosis patients and 5 specimens from normal control, was downloaded from GEO datasets. Differentially expressed genes (DEGs) were sorted with regard to AL amyloidosis versus normal control group using Limma package. The gene enrichment analyses including GO and KEGG pathway were performed using DAVID website subsequently. Furthermore, the protein–protein interaction (PPI) network for DEGs was constructed by Cytoscape software and STRING database. DEGs were mapped to the connectivity map datasets to identify potential molecular agents of AL amyloidosis.Results: A total of 1464 DEGs (727 up-regulated, 737 down-regulated) were identified in AL amyloidosis samples versus control samples, these dysregulated genes were associated with the dysfunction of ribosome biogenesis and immune response. PPI network and module analysis uncovered that several crucial genes were defined as candidate genes, including ITGAM, ITGB2, ITGAX, IMP3 and FBL. More importantly, we identified the small molecular agents (AT-9283, Ritonavir and PKC beta-inhibitor) as the potential drugs for AL amyloidosis.Conclusion: Using bioinformatics approach, we have identified candidate genes and pathways in AL amyloidosis, which can extend our understanding of the cause and molecular mechanisms, and these crucial genes and pathways could act as biomarkers and therapeutic targets for AL amyloidosis.Keywords: light chain amyloidosis, bioinformatics approach, differentially expressed genes, candidate genes, therapeutic agent

Shaohui Zheng,1–3,* Min Zhang,2,* Hongyan Bai,2 Meijuan He,2 Lina Dong,2 Lulu Cai,2 Mingming Zhao,2 Qi Wang,2 Kai Xu,1–3 Jingjing Li1–3 1Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of China; 2School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, People’s Republic of China; 3Institute of Medical Imaging and Digital Medicine, Xuzhou Medical University, Xuzhou 221004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingjing Li; Kai Xu Email qingchao0124@163.com; xkpaper@163.comBackground: Early diagnosis of renal cell carcinoma is extremely significant for the effective treatment of kidney cancer. The development of AS1411 aptamer modified Mn-MoS2 QDs provides a promising fluorescence/magnetic resonance (MR) dual-modal imaging probe for the precise diagnosis of renal clear cell carcinoma.Methods: In this work, Mn-MoS2 QDs were synthesized through a simple “bottom-up” one-step hydrothermal method. AS1411 aptamer was modified on the Mn-MoS2 QDs to improve the specificity to renal cell carcinoma. The characteristics of Mn-MoS2 QDs were confirmed by transmission electronic microscopy (TEM), atomic force microscope (AFM), X-ray photoelectron spectrometer (XPS), photoluminescence (PL) emission spectra, etc. Cellular fluorescence labelling was investigated using the Mn-MoS2 QDs and AS1411-Mn-MoS2 QDs. The T1-weighted MR imaging was assessed by the in vitro MR cell imaging and in vivo MR imaging. Finally, the long-term toxicity of Mn-MoS2 QDs was investigated by the hematology and histological analysis.Results: The prepared Mn-MoS2 QDs exhibited excellent aqueous property, intense fluorescence, low toxicity, high quantum yield of 41.45% and high T1 relaxivity of 16.95 mM−1s−1. After conjugated with AS1411 aptamer, the AS1411-Mn-MoS2 QDs could specifically fluorescently label the renal carcinoma cells and present a specific MRI signal enhancement in the tumor region of mice bearing renal carcinoma tumors. Furthermore, Mn-MoS2 QDs revealed low toxicity to the mice via hematology and histological analysis.Conclusion: These results demonstrated the potential of AS1411-Mn-MoS2 QD as a novel nanoprobe for targeted MR imaging and fluorescence labelling of renal cell carcinoma.Keywords: manganese-doped molybdenum disulfide quantum dots, renal cell carcinoma, magnetic resonance imaging, cell fluorescence labelling

Sijin Li,1–3 Qishu Zhang,1–3 Hongmei Bai,1–3 Weiwei Huang,1–3 Congyan Shu,1–3 Chao Ye,1–3 Wenjia Sun,1–3 Yanbing Ma1–3 1Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, People’s Republic of China; 2Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Kunming, People’s Republic of China; 3Yunnan Engineering Research Center of Vaccine Research and Development on Severe Infectious Disease, Kunming, People’s Republic of ChinaCorrespondence: Yanbing MaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, 935 Jiaoling Road, Kunming 650118, People’s Republic of ChinaTel +86 871 6833 9287Fax +86 871 6833 4483Email yanbingma@126.comBackground: Vaccines are one of the most promising strategies for immunotherapy of HPV associated tumors; however, they generally lack significant clinical efficacy at present. This inefficacy might be due to inefficient generation of anti-tumor cellular immune responses.Purpose: This study aimed to assess the potential of using self-assembled nanofibers as a new vaccine platform to elicit potent HPV antigen - specific anti-tumor immunity.Methods: A HPV16 E744-62 peptide was chemically appended to the N terminus of self-assembling peptide Q11. The nanofibers were prepared and used to immunize mice through a preventive or therapeutic strategy in a TC-1 graft tumor model.Results: Preventive immunization with nanofibers almost completely suppressed the growth of primarily grafted TC-1 tumors and even a re-challenge of tumor cells after a six-week rest. Therapeutic immunization significantly increased the levels of effector Th1 cells, CTLs and the cytokines IFN-γ and TNF-α in E7 peptide-stimulated splenocytes, and the immunization reduced Th2, MDSC and IL-4 contents compared to the controls. The nanofiber immunization significantly suppressed the growth of established tumors and achieved 66.7% and 50% tumor-free in mice carrying 2–3 mm tumors and even larger tumors with a diameter of 5–6 mm respectively. In addition, the nanofibers were more efficient than the corresponding unassembled peptides for the treatment of established larger size tumors.Conclusion: The results indicated that self-assembling nanofibers could elicit robust HPV antigen -specific anti-tumor cellular immunity and are a potent antigen delivery system for HPV related tumor vaccines.Keywords: self-assembling nanofibers, cellular immunity, tumor, vaccine, human papillomavirus, HPV