Search

Zhongbao Zuo,1,&ast; Jing Wu,1,&ast; Miaochan Wang,1 Rui Wu,2 Xiaojing Zhang,2 Lanlan Hu,1 Huaizhong Cui,1 Ting Feng,3 Aifang Xu,1 Shourong Liu2 1Department of Clinical Laboratory, Hangzhou Xixi Hospital, Zhejiang, 310023, People’s Republic of China; 2Department of Hepatology, Hangzhou Xixi Hospital, Zhejiang, 310023, People’s Republic of China; 3Ultrasound Department, Hangzhou Xixi Hospital, Zhejiang, 310023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aifang Xu; Shourong Liu, Email 13616500869@163.com; lsr85463990@126.comIntroduction: This study aimed to explore serum HBV pre-genomic RNA (pgRNA) levels and its associated factors among HBV-infected patients in the real world.Methods: This retrospective cohort study was conducted from May 10, 2023, to January 15, 2024. Univariate logistic analysis for positive serum HBV pgRNA was performed first, and variables with statistical significance were included in a multivariate logistic model. A decreasing trend of serum HBV pgRNA and HBV DNA levels was also detected first by univariate logistic regression and then by multivariate logistic regression.Results: 482 patients were included in our analysis at baseline, and 191 patients were followed up. Multivariate logistic regression revealed that positive HBV DNA (AOR: 2.63, 95% CI: 1.46– 4.75, P=0.001), ≥ 1000 hBsAg (AOR: 2.29, 95% CI: 1.08– 4.89, P=0.03), positive HBeAg (AOR: 28.26, 95% CI: 15.2– 52.55, P< 0.001), and ALP (AOR: 1.01, 95% CI: 1.001– 1.02, P=0.03) were positively correlated with positive HBV pgRNA at baseline. Two independent multivariate logistic regression models were constructed for the decreasing trend of serum HBV pgRNA and HBV DNA for the 191 follow-up patients. Results showed that the decreasing trend of HBV pgRNA was positively correlated with positive baseline HBV DNA (AOR: 4.60, 95% CI: 1.84– 11.51, P=0.001), baseline HBsAg ≥ 1000 IU/mL (AOR: 8.74, 95% CI: 1.09– 70.10, P=0.04), and HDL (AOR: 5.01, 95% CI: 1.28– 19.66, P=0.02). The decreasing trend of HBV DNA was positively correlated with positive baseline HBV pgRNA (AOR: 3.80, 95% CI: 2.00– 8.83, P< 0.001) and AST (AOR: 1.06, 95% CI: 1.03– 1.08, P< 0.001).Conclusion: Our study revealed that HBV DNA, HBsAg, HBeAg, and ALP were significantly correlated with positive HBV pgRNA at baseline. The baseline HBV DNA, HBsAg, and HDL were significantly correlated with decreasing levels of HBV pgRNA. A decreasing trend of HBV DNA significantly correlated with patients’ baseline HBV pgRNA and AST.Keywords: chronic hepatitis B, HBsAg, HBV pgRNA, HBV DNA

Yinying Li,1 Qiuming Li,2 Haihua Lei,3 Xiaorong Wei,4 Tao Feng,2 Huajiao Qin,2 Hongchun Huang,2 Minchao Duan1,2 1The Second Clinical Medical College, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 3Radiological department, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China; 4Clinical Laboratory, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of ChinaCorrespondence: Minchao Duan, Department of Respiratory and Critical Care Medicine, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China, Tel/Fax +86 15507711966, Email musicladyd@sina.comBackground: Pulmonary infection is a common clinical complication associated with glucocorticoid. There have been no reported cases of mixed infections involving Nocardia and Pneumocystis jirovecii combined with anti-synthetase syndrome (ASS) activity.Methods: This study conducted a retrospective analysis of the clinical data from a patient with active ASS, treated for a pulmonary coinfection.Results: The patient exhibited fever, asthma, and cough as initial symptoms. Chest CT scan revealed multiple infiltration shadows, consolidation shadows, nodules, mass shadows, and internal cavities in both lungs. BALF mNGS detected Nocardia terpene and Pneumocystis jiroveci. Treatment with sulfamethoxazole/trimethoprim and corticosteroids led to an improvement. However, the patient experienced recurrent fever and a new rash with the reduction of the glucocorticoid dosage. Further investigation identified positive anti-Jo-1 and anti-Ro-52 antibodies and myogenic lesions on electromyography, which confirmed the diagnosis of ASS. Following treatment with immunoglobulin, methylprednisolone, and cyclosporine, the patient’s condition significantly improved.Conclusion: Immunodeficiency patients are susceptible to opportunistic infections. mNGS is valuable for diagnosis and treatment. Although the image of Nocardia terpene and Pneumocystis jiroveci infections lack specificity, they exhibit distinctive features. Should fever and skin lesions reoccur post-effective anti-infective therapy, it is imperative to explore non-infectious causes and expedite autoantibody testing.Keywords: co-infection, Nocardia terpene, Pneumocystis jiroveci, anti-synthetase syndrome, anti-Ro-52 antibody, anti-Jo-1 antibody

Tongfei Feng,1– 3,&ast; Yanlin Zhou,1,3,&ast; Bin Lv,1,3 Lijun Cai1,3 1Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hubin Campus, Hangzhou, 310006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lijun Cai; Bin Lv, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel +86-571-86613545, Fax +86-571-87073763, Email 20051018@zcmu.edu.cn; lvbin@medmail.com.cnPurpose: Through network pharmacology combined with molecular docking and in vivo validation, the study examines the unexplored molecular mechanisms of Tongxieyaofang (TXYF) in the treatment of irritable bowel syndrome (IBS). In particular, the potential pharmacological mechanism of TXYF alleviating IBS by regulating CHRM3 and intestinal barrier has not been studied.Patients and Methods: LC-MS technique and TCMSP database were used in combination to identify the potential effective components and target sites of TXYF. Potential targets for IBS were obtained from Genecards and OMIM databases. PPI and cytoHub analysis for targets. Molecular docking was used to validate the binding energy of effective components with related targets and for visualization. GO and KEGG analysis were employed to identify target functions and signaling pathways. In the in vivo validation, wrap restraint stress-induced IBS model was employed to verify the change for cytoHub genes and CHRM3 expression. Furthermore, inflammatory changes of colon were observed by HE staining. The changes of Ach were verified by ELISA. IHC and WB validated CHRM3 and GNAQ/PLC/MLCK channel variations. AB-PAS test and WB test confirmed the protection of TXYF on gut barrier. The NF-κB/MLCK pathway was also verified.Results: In TXYF decoction, LC-MS identified 559 chemical components, with 23 remaining effective components after screening in TCMSP. KEGG analysis indicated that calcium plays a crucial role in TXYF treated for IBS. Molecular docking validated the binding capacity of the effective components Naringenin and Nobiletin with cytoHub-gene and CHRM3. In vivo validation demonstrated that TXYF inhibits the activation of Ach and CHRM3 in IBS, and inhibits for the GNAQ/PLC/MLCK axis. Additionally, TXYF downregulates TNF-α, MMP9, and NF-κB/MLCK, while modulating goblet cell secretion to protect gut barrier.Conclusion: TXYF inhibits Ach and CHRM3 expression, regulating the relaxation of intestinal smooth muscle via GNAQ/PLC/MLCK. Additionally, TXYF inhibits NF-κB/MLCK activated and goblet cell secretion to protect gut barrier. Keywords: irritable bowel syndrome, tongxieyaofang decoction, Ach, CHRM3, GNAQ/PCL/MLCK, gut barrier

Yuanyuan Hu,1,2,&ast; Yuening Jin,1,2,&ast; Bowen Hu,3 Tingyong Feng,3 Yuan Zhou1,2,4 1CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China; 2Department of Psychology, University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China; 3Faculty of Psychology, Southwest University, Chongqing, 400715, People’s Republic of China; 4The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Zhou, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Road, Chaoyang District, Beijing, 100101, People’s Republic of China, Email zhouyuan@psych.ac.cn Tingyong Feng, Faculty of Psychology, Southwest University, No. 2, Tian Sheng Road, Beibei, ChongQing, 400715, People’s Republic of China, Email fengty0@swu.edu.cnIntroduction: Money source influences risk-taking behaviors. Although studies consistently indicated that individuals demonstrate a higher propensity to make risky investments when utilizing non-labor income as opposed to labor income, explanations as to why non-labor income leads to continuously blowing money into risky investments are scarce.Methods: The current study leverages a computational modeling approach to compare the differences in the dynamic risk investment process among individuals endowed with income from different sources (ie, non-labor income vs labor income) to understand the shaping force of higher risk-taking propensity in individuals with non-labor income. A total of 103 participants were recruited and completed the Balloon Analogue Risk Task (BART) with an equal monetary endowment, either as a token for completion of survey questionnaires (representing labor income) or as a prize from a lucky draw game (representing non-labor income).Results: We found that individuals endowed with non-labor income made more risky investments in BART compared to those with labor income. With computational modeling, we further identified two key differences in the dynamic risk investment processes between individuals endowed with labor and those with non-labor income. Specifically, individuals endowed with non-labor income had a higher preset expectation for risk-taking and displayed desensitization towards losses during risk investments, in contrast to individuals with labor income.Discussion: This study contributed to a better understanding of the psychological mechanisms of why individuals make more risk-taking behaviors with non-labor income, namely higher preset expectations of risk-taking and desensitization towards losses. Future research could validate these findings across diverse samples with varying backgrounds and adopt different manipulations of labor and non-labor income to enhance the external validity of our study.Keywords: non-labor income, balloon analogue risk task, computational modeling, hierarchical Bayesian analysis, reinforcement learning

Pengwei Hou,1,&ast; Yang Yang,2,&ast; Ziqi Li,1,&ast; Dan Ye,2 Li Chen,1 Tianshun Feng,3 Jiateng Zeng,4 Liangfeng Wei,1 Shousen Wang1,5 1Department of Neurosurgery, Fuzong Clinical Medical College of Fujian Medical University (The 900TH Hospital), Fuzhou, Fujian Province, People’s Republic of China; 2Fuzhou General Teaching Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Neurosurgery, Dongfang Affiliated Hospital of Xiamen University School of Medicine, Xiamen University, Xiamen, Fujian Province, People’s Republic of China; 4Department of Neurosurgery, Neurosurgery Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Fujian Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Neurovascular Diseases, Fuzhou, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangfeng Wei; Shousen Wang, Department of Neurosurgery, Fuzong Clinical Medical College of Fujian Medical University (The 900TH Hospital), No. 156, Xierhuanbei Road, Fuzhou, Fujian Province, 350025, People’s Republic of China, Tel +8613960760177 ; +8613950482966, Email wlf74@163.com; wshsen1965@126.comPurpose: The activation of the inflammatory response is regarded as a pivotal factor in the pathogenesis of TBI. Central nervous system infection often leads to the exacerbation of neuroinflammation following TBI, primarily caused by Gram-negative bacteria. This study aims to elucidate the effects of the novel anti-inflammatory drug TAK-3 on LPS-induced neuroinflammation in TBI rats.Methods: In conjunction with the rat controlled cortical impact model, we administered local injections of Lipopolysaccharide to the impact site. Subsequently, interventions were implemented through intraperitoneal injections of TAK-3 and NF-κB activitor2 to modulate the TLR4/NF-κB axis The impact of LPS on neurological function was assessed using mNSS, open field test, and brain water content measurement. Inflammatory markers, including TNF-α, IL-1β, IL-6 and IL-10 were assessed to evaluate the condition of neuritis by Elisa. The activation of the TLR-4/NF-κB signaling pathway was detected by immunofluorescence staining and Western blot to assess the anti-inflammatory effects of TAK-3.Results: The administration of LPS exacerbated neurological damage in rats with TBI, as evidenced by a reduction in motor activity and an increase in anxiety-like behavior. Furthermore, LPS induced disruption of the blood-brain barrier integrity and facilitated the development of brain edema. The activation of microglia and astrocytes by LPS at the cellular and molecular levels has been demonstrated to induce a significant upregulation of neuroinflammatory factors. The injection of TAK-3 attenuated the neuroinflammatory response induced by LPS.Conclusion: The present study highlights the exacerbating effects of LPS on neuroinflammation in TBI through activation of the TLR-4/NF-κB signaling pathway. TAK-3 can modulate the activity of this signaling axis, thereby attenuating neuroinflammation and ultimately reducing brain tissue damage.Keywords: NF-κB activator2, CNS infection, CCI, inflammation, TAK-3

Baohu Zhang,1,&ast; Jie Zhou,1,&ast; Guancong Xie,2,&ast; Li Zhang,1 Yang Zhang,1 Kangli Xu,1 Tianyuan Feng,1 Shucai Yang1 1Department of Clinical Laboratory, Pingshan General Hospital, Southern Medical University (Pingshan District People’s Hospital of Shenzhen), Shenzhen, Guangdong, People’s Republic of China; 2Department of Cardiovascular Medicine, Pingshan General Hospital, Southern Medical University (Pingshan District People’s Hospital of Shenzhen), Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shucai Yang; Tianyuan Feng, Email shucaiyang@link.cuhk.edu.hk; psyyfty@sina.comAbstract: S. mitis/oralis has been previously reported in isolated cases of bacterial endocarditis and liver abscesses. Its presence in urine is generally considered a contaminant. A 66-year-old male patient was admitted to the hospital due to recurrent chest tightness and four-year history of exertional dyspnea. On the second day of admission, the patient presented with urgent and frequent urination, as well as dysuria. Both initial and subsequent urine cultures showed S. mitis/oralis infection, with polymorphonuclear leukocyte phagocytosis observed in the second sample. MALDI-TOF results confirmed the isolated strain as S. mitis/oralis. Drug susceptibility testing revealed multidrug resistance to penicillin, ceftriaxone, cefepime, levofloxacin, ofloxacin, and tetracycline, but sensitivity to quinupristin/dalfopristin, vancomycin, and linezolid. The clinician then prescribed vancomycin for anti-infective treatment, which proved effective. Keywords: S. mitis/oralis, UTI, MDR, phagocytosisKeywords: Streptococcus mitis/oralis, UKI, multidrug resistant, phagocytosis

Jin-ning Wang,1,&ast; Wei Xie,2,&ast; Da-Wei Song,1,&ast; Jun Zou,1 Qi Yan,1 Tao Feng,1 Sheng-yang Jin,1 Chao Yang,1 Zong-ping Luo,1,3 Jun-jie Niu1 1Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Orthopaedics, Suzhou Ninth People’s Hospital, Suzhou, Jiangsu, People’s Republic of China; 3Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zong-ping Luo, Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China, Tel +86-512-67781351, Email zongping_luo@yahoo.com Jun-jie Niu, Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China, Tel +86-512-67780111, Email jjnewzzzx@sina.comBackground: Recurrent of local kyphosis after percutaneous kyphoplasty (PKP) is rarely reported and discussed. Literatures reported that re-kyphosis is usually a consequence of refractures of augmented or adjacent vertebra. However, whether re-kyphosis should be considered as a complication of refractures and has an impact on clinical efficacy of PKP during follow-up time is unknown. The purpose of this study is to evaluate the related risk factors and clinical significance of the recurrent of local kyphosis in osteoporotic vertebral fracture (OVF) patients without refractures.Patients and Methods: A total of 143 patients who underwent single-level PKP were recruited and assigned into the re-kyphosis group and non-re-kyphosis group. Clinical and radiographic data were collected and compared between the two groups. Then, multivariate logistic regression analyses were conducted to identify the related risk factors.Results: During follow-up, 16 of the 143 patients presented postoperative re-kyphosis. The average local kyphosis angle increased from 11.81± 8.60° postoperatively to 25.13± 8.91° at the final follow-up which showed a statistically significant difference (p< 0.05). Both groups had significant improvements in postoperative visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores compared to their preoperative values (p< 0.05). However, in the re-kyphosis group at final follow-up, the VAS and ODI scores showed worsening compared to the postoperative scores. Logistic regression analysis showed that disc–endplate complex injury (OR=17.46, p=0.003); local kyphosis angle correction (OR=1.84, p< 0.001); and vertebral height restoration (OR=1.15, p=0.003) were risk factors for re-kyphosis.Conclusion: Re-kyphosis is not rare in patients with osteoporotic vertebral fracture and tends to have an inferior prognosis following PKP surgery. Patients with disc–endplate complex injury and more correction of vertebral height and kyphosis angle are at a higher risk for re-kyphosis after PKP surgery than others.Keywords: percutaneous kyphoplasty, risk factors, re-kyphosis, disc–endplate complex injury, clinical efficacy

Hu Ren, Tao Feng, Yaning Hu, Guangqing Yao, Dahai Yu, Jianhui Cao Department of Orthopedic Surgery, Shijiazhuang People’s Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Jianhui Cao, Department of Orthopedic Surgery, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email cjhspine@163.comPurpose: This retrospective study aimed to verify whether the use of a balloon in balloon kyphoplasty (BKP) could offer a higher degree of vertebral height restoration and deformity correction than percutaneous vertebroplasty (PVP) after adjustment for preoperative dynamic fracture mobility. We expect that this research will help surgeons to determine the optimum operation choice (PVP or BKP) for treating osteoporotic vertebral compression fractures (OVCFs).Patients and Methods: We evaluated retrospectively 262 patients who were treated by PVP or BKP for acute, single-level OVCF at our institution from July 2015 to July 2019. According to the presence or absence of dynamic fracture mobility, the patients were divided into two groups: mobile group and fixed group. We compared the changes in the vertebral height and kyphotic angle for PVP and BKP, respectively, within each group.Results: In the mobile group, the anterior vertebral height restoration (BKP group, 8.73± 5.27%; PVP group, 2.96± 1.59%), middle vertebral height restoration (BKP group, 7.58± 5.18%; PVP group, 2.74± 1.24%) and kyphotic angle correction (BKP group, 4.41± 4.46°; PVP group, 1.38± 1.60°) due to percutaneous vertebral augmentation technique itself were more obvious in BKP group compared with PVP group (P < 0.05). The BKP group has lower incidence of bone cement leakage (BKP group, 10.17%; PVP group, 25.53%, P < 0.05). In the fixed group, differences from comparison of changes were not statistically significant between PVP and BKP (P > 0.05).Conclusion: The use of a balloon in BKP could offer greater kyphosis correction, higher vertebral body height restoration, and lower cement leakage rate than PVP if a fractured vertebral body existed dynamic mobility. However, all these advantages of BKP over PVP are not obvious and could be overrated for a fixed fracture exhibited no mobility. BKP is recommended for a fractured vertebral body with dynamic mobility. PVP is suggested for a fixed fractured vertebral body with no mobility as it produces similar capability of vertebral height restoration, kyphosis correction, and cement leakage as BKP.Keywords: dynamic fracture mobility, optimum operation choice, osteoporotic vertebral compression fracture, balloon kyphoplasty, percutaneous vertebroplasty

Siyuan Huang,1,&ast; Tao Feng,2,&ast; Jing Wang,1 Liang Dong3 1Department of Respiratory, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Respiratory Medicine, Shengli Oilfield Central Hospital, Dongying, People’s Republic of China; 3Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Dong, Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, 250014, People’s Republic of China, Tel +86-13505401207, Email dl5506@126.comBackground: Interleukin (IL)-36α, IL-36β, and IL-36γ belong to the IL-36 family and play an important role in the pathogenesis of many diseases. Chronic obstructive pulmonary disease (COPD) may be correlated with IL-36; however, the specific role of IL-36 in COPD is unclear. In this study, we aimed to clarify whether IL-36 could be an indicator for determining COPD severity and the specific nature of the pro-inflammatory effects of IL-36 in COPD.Methods: A total of 70 patients with COPD and 20 control subjects were included in this study. We collected peripheral blood samples from both the groups, analyzed the blood cell fractions by routine blood examination, and measured the serum levels of IL-36α, IL-36β, and IL-36γ by performing polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, the correlation between the number of neutrophils and eosinophils and the level of IL-36 was also analyzed.Results: We found that level of IL-36 in patients with COPD was positively correlated with the number of neutrophils but not with eosinophils, whereas the correlation was not found in the control group. Moreover, the level of IL-36 was negatively correlated with the level of lung function of patients with COPD, and the levels of IL-36α, IL-36β, and IL-36γ increased with advancing disease severity.Conclusion: In COPD, the pro-inflammatory effect of IL-36 is closely related to neutrophils, and hence, IL-36 might be considered a novel biomarker for determining COPD severity.Keywords: chronic obstructive pulmonary disease, IL-36, neutrophils, inflammation

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

Meimei Zhang,1,2 Huimin Chen,3 Genliang Liu,1,2 Xuemei Wang,1,2 Zhan Wang,1,2 Tao Feng,1,2 Yumei Zhang2,4 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, People’s Republic of China; 3Department of Neurology, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 4Department of Rehabilitation, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Tao FengDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of ChinaEmail bxbkyjs@sina.comYumei ZhangDepartment of Rehabilitation, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of ChinaEmail zhangyumei95@aliyun.comPurpose: Lacunae are imaging biomarkers of cerebral small vessel disease (CSVD) and are correlated with the degree of gait instability in Parkinson’s disease (PD). The wearing-off phenomenon (WO) occurs more frequently in PD patients as disease progresses. The present study aimed to investigate the overall impact of the quantity and location of lacunae on the WO in PD.Patients and Methods: This retrospective, single-center study included 315 consecutive eligible patients with PD from Beijing Tiantan Hospital from May 2016 to August 2018. We collected data on demographics and clinical features, assessed lacunae and examined the presence of the WO. The association between lacunae and the WO was assessed using a binary logistic regression model.Results: The number of lacunae was significantly associated with the WO in patients with PD according to a model adjusted for age at onset, disease duration, Hoehn–Yahr (H-Y) staging, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) total score and levodopa equivalent daily dosage (LEED) (P=0.037, OR 1.156, 95% CI 1.009, 1.325) and to a model further adjusted for other CSVD imaging biomarkers (P=0.046, OR 1.172, 95% CI 1.003, 1.369). Following additional adjustment for other potential confounders, the association remained significant (P=0.043, OR 1.195, 95% CI 1.005, 1.421). Lacunae in subcortical areas (P=0.004, OR 0.498, 95% CI 0.308, 0.803) and basal ganglia (P=0.046, OR 1.616, 95% CI 1.009, 2.587), especially in the caudate nuclei (P=0.023, OR 1.104, 95% CI 0.185, 0.881), were significantly associated with the WO in PD patients.Conclusion: Our finding highlights the significant association between lacune and the WO, and lacunae may be an independent contributor to the WO in PD patients. Promoting neurovascular health may prevent the progression of the WO in PD patients.Keywords: Parkinson’s disease, wearing-off phenomenon, lacunae, cerebral small vessel disease

Jingxian Duan,1 Yuling Wu,2 Jikui Liu,3 Jiajia Zhang,2 Zhichao Fu,2 Tieshan Feng,2 Ming Liu,2 Jie Han,2 Zhicheng Li,1 Shifu Chen1,2 1Department of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 2Department of Oncology, HaploX Biotechnology Co. Ltd, Shenzhen 518000, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, People’s Republic of ChinaCorrespondence: Shifu ChenDepartment of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of ChinaTel +86 135 1042 7830Email sf.chen@siat.ac.cnAbstract: Being one of the most lethal cancers that exhibit high levels of heterogeneity, hepatocellular carcinoma (HCC) is associated with diverse oncogenic pathways underpinned by varied driver genes. HCC can be induced by different etiological factors including virus infection, toxin exposure or metabolic disorders. Consequently, patients may display varied genetic profiles, and may respond differently to the treatments involving inhibition of target pathways. These DNA/RNA mutations, copy number variations, chromatin structural changes, aberrant expression of non-coding RNAs and epigenetic modifications were considered as biomarkers in the application of precision medication. To explore how genetic testing could contribute to early diagnosis, prognosis, treatment and postoperative monitoring of HCC, we conducted a systematic review of genetic markers associated with different pathologies. Moreover, we summarized on-going clinical trials for HCC treatment, including the trials for multiple kinase inhibitors and immune checkpoint blockade (ICB). The efficacy of ICB treatment in HCC is not as good as what was observed in lung cancer and melanoma, which might be due to the heterogeneity of the microenvironment of the liver.Keywords: genetic biomarkers, hepatocellular carcinoma, genomic sequencing, clinical trials

Ting Feng,1,* Yumeng Wei,1,* Robert J Lee,2 Ling Zhao1 1Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA *These authors contributed equally to this work Abstract: Curcumin (CUR) is a yellow polyphenolic compound derived from the plant turmeric. It is widely used to treat many types of diseases, including cancers such as those of lung, cervices, prostate, breast, bone and liver. However, its effectiveness has been limited due to poor aqueous solubility, low bioavailability and rapid metabolism and systemic elimination. To solve these problems, researchers have tried to explore novel drug delivery systems such as liposomes, solid dispersion, microemulsion, micelles, nanogels and dendrimers. Among these, liposomes have been the most extensively studied. Liposomal CUR formulation has greater growth inhibitory and pro-apoptotic effects on cancer cells. This review mainly focuses on the preparation of liposomes containing CUR and its use in cancer therapy. Keywords: curcumin, liposomes, drug delivery, bioavailability, cancer

QiHong Wu,1 RongRong Jin,2 Ting Feng,1 Li Liu,2 Li Yang,2 YuHong Tao,3 James M Anderson,4,5 Hua Ai,2,6 Hong Li1,3 1Key Laboratory of Obstetrics, Gynecology, Pediatric Disease, and Birth Defects, Ministry of Education, West China Second University Hospital, 2National Engineering Research Center for Biomaterials, 3Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China; 4Department of Biomedical Engineering, 5Department of Pathology, Case Western Reserve University, Cleveland, OH, US; 6Department of Radiology, West China Hospital, Sichuan University, Chengdu, China Abstract: Superparamagnetic iron oxide nanoparticles have been widely used in biomedical applications, but understanding of their interactions with the biological immune system is relatively limited. This work is focused on dextran-coated iron oxide nanoparticles and their induced autophagy in human monocytes. We found that these nanoparticles can be taken up by human monocytes, followed by localization within vesicles or free in cytoplasm. Autophagosome formation was observed with increased expression of LC3II protein, the specific marker of autophagy. The autophagy substrate p62 was degraded in a dose-dependent manner, and autophagy was blocked by autophagy (or lysosome) inhibitors alone or along with iron oxide nanoparticles, indicating that autophagosome accumulation was mainly due to autophagy induction, rather than blockade of autophagy flux. Interestingly, iron oxide nanoparticles increased the viability of human monocytes, but the mechanism was not clear. We further found that inhibition of autophagy mostly attenuated the survival of cells, with acceleration of the inflammation induced by these nanoparticles. Taken together, autophagic activation in human monocytes may play a protective role against the cytotoxicity of iron oxide nanoparticles. Keywords: autophagy, cytotoxicity, human monocytes, inflammation, iron oxide nanoparticles

Amorphous alloys or metallic glasses have attracted significant interest in the materials science and engineering communities due to their unique physical, mechanical, and chemical properties. The viscous flow of amorphous alloys exhibiting high strain rate sensitivity and homogeneous deformation is considered to be an important characteristic in thermoplastic forming processes performed within the supercooled liquid region because it allows superplastic-like deformation behavior. Here, the correlation between the superheated liquid fragility, and the onset temperature of crystallization for Al-based alloys, is investigated. The activation energy for viscous flow of the liquid is also investigated. There is a negative correlation between the parameter of superheated liquid fragility and the onset temperature of crystallization in the same Al-based alloy system. The activation energy decreases as the onset temperature of crystallization increases. This indicates that the stability of a superheated liquid can affect the thermal stability of the amorphous alloy. It also means that a liquid with a large superheated liquid fragility, when rapidly solidified, forms an amorphous alloy with a low thermal stability.

Millisecond magnetars are widely suggested as the central engines powering hydrogen-poor superluminous supernovae (SLSNe). These magnetars primarily lose huge rotational energy through gravitational wave radiation (GWR) and magnetic dipole radiation (MDR), with MDR serving as an energy source for SLSNe. We study the evolution of the magnetar spin, magnetic inclination angle, and the resulting thermal radiative luminosity of the SLSNe, where the impacts of the nucleon–nucleon short-range correlation, the mass and initial spin of the magnetar, and the density-dependent symmetry energy of the dense nuclear matter on the evolution are discussed. The relativistic mean-field theory is employed to calculate the nuclear matter properties, and we particularly concentrate on the time- and space-dependent bulk viscosity, which is crucial for the magnetic inclination angle evolution. It is found that the nucleon–nucleon short-range correlation weakens the damping of bulk viscosity of dense matter and therefore inhibits the growth of magnetic inclination angle, and it reduces the MDR (GWR) peak luminosity of a canonical magnetar by several times while it raises the peak thermal radiation luminosity of SLSNe by several times. For magnetars with non-rotating mass obviously lower than the |$1.4 \, \rm M_\odot$| with slow initial rotation, the magnetic inclination angle is more likely to evolve towards 0 deg quickly, and these magnetars are not suitable as the central engine for SLSNe. Within the 'family' of FSUGarnet interaction, a stiffer symmetry energy gives a lower threshold of direct Urca process and hence gives a much larger bulk viscosity coefficient, and thus it promotes the growth of the magnetic inclination angle and the GWR for canonical stars but reduces the peak brightness of SLSNe significantly. [ABSTRACT FROM AUTHOR]