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Rongge Jiang,1 Haibai Liu,2 Xue Jiang,2 Ding Wang,2 Xiaoyu Li,2 Yi Shang3 1Neurosurgery Department 1, Baoding No.1 Central Hospital, Baoding, 071000, People’s Republic of China; 2Department of Nursing, Shijiazhuang Medical College, Shijiazhuang, 050599, People’s Republic of China; 3Department of Mammary, Shijiazhuang Fourth Hospital, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Xiaoyu Li, Shijiazhuang Medical College, No. 1 Tongxin Road, Lingshou County, Shijiazhuang, Hebei, 050599, People’s Republic of China, Tel + 8613603117321, Email lixiaoyu_li03@126.comObjective: This study explores the impact of a nursing intervention grounded in empowerment theory, focusing on behavioral change, on brain metastasis patients post-breast cancer surgery.Methods: Between June 2021 and June 2023, 102 patients diagnosed with brain metastasis after breast cancer surgery at Bao Ding No.1 Central Hospital were randomized into two groups. The control group (51 patients) received standard nursing care, while the observation group (51 patients) participated in a behavioral change nursing intervention influenced by empowerment theory. The evaluation metrics included measures of negative emotions, compliance with treatment protocols, overall quality of life, and nursing satisfaction, assessed at multiple time points during the study period.Results: The intervention led to significant reductions in negative emotions for all patients when compared to their pre-intervention statuses, with the observation group exhibiting notably lower depression and anxiety scores at one and three months post-intervention (P < 0.05). Additionally, this group achieved higher compliance scores and demonstrated greater improvements in quality of life than the control group (P < 0.05). Nursing satisfaction was also significantly higher in the observation group, with 96.08% reporting high satisfaction compared to 80.39% in the control group (P < 0.05).Conclusion: Implementing a nursing intervention that emphasizes behavioral changes and leverages empowerment theory significantly enhances the quality of life, reduces negative emotions, boosts compliance with treatment, and increases nursing satisfaction among patients with brain metastasis following breast cancer surgery. This suggests that such interventions could be a valuable component of postoperative care for this patient population.Keywords: behavioral change, empowerment theory, negative emotions, nursing intervention, brain metastasis, breast cancer, quality of life

Qiaoling Wei,1– 3,&ast; Liangliang Niu,1– 3,&ast; Xianjin Zhou,4 Han Chen,1,2 Rui Jiang1– 3 1Department of Ophthalmology, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, People’s Republic of China; 3Ocular Trauma Center, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 4Department of Ophthalmology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Jiang; Han Chen, Tel +86-21-64377134, Fax +86-21-6477134, Email 2jiang@163.com; avnus@163.comPurpose: To evaluate the effects of retinal surgery on the ocular surface and corneal subbasal nerve plexus (SNP).Methods: Ninety-eight patients undergoing 23-gauge pars plana vitrectomy for various vitreoretinal disorders were prospectively studied. We collected detailed operative and perioperative data, measuring dry eye syndrome (DED) severity and Ocular Surface Disease Index (OSDI) scores before surgery and at postoperative intervals. In vivo confocal microscopy (IVCM) quantified SNP and dendritic cell (DC) densities.Results: Fifty-three patients were analyzed. Post-surgery, OSDI scores rose from a baseline of 5.5 ± 3.5 to 12.24 ± 6.5 at one month, later reducing to 7.8 ± 4.0 after a year. DED severity increased from 0.6 ± 0.6 initially to 1.6 ± 0.6 at three months, returning to near baseline (0.9 ± 0.6) one year after surgery. DC densities increased notably by the third (58.85 ± 75.6 cells/mm²) and ninth (59.95 ± 86 cells/mm²) postoperative months, especially in patients undergoing combined phacoemulsification, vitrectomy, and C3F8 gas tamponade. SNP parameters, particularly nerve fiber density and length, showed significant declines one month post-surgery, not recovering to baseline levels within a year. Fiber density dropped from 19.06 ± 8.3 fibers/mm² preoperatively to 4.68 ± 4.8 fibers/mm² at one month, partially recovering to 10.64 ± 8.2 fibers/mm² at twelve months. Fiber length decreased from 13.31 ± 3.2 mm/mm² to 6.86 ± 3.4 mm/mm² at one month, later improving to 9.81 ± 4.5 mm/mm² at twelve months, notably in patients with silicone oil (SiO2) tamponade.Conclusion: Retinal surgery, especially when combined with phacoemulsification and C3F8 or SiO2 tamponade, significantly affects ocular surface integrity and SNP density, with these changes lasting up to a year. Expanded studies with more patients and longer follow-up, using finer 25- and 27-gauge vitrectomy tools, are recommended to confirm and extend these findings.Keywords: corneal subbasal nerve plexus, ocular surface, retinal surgical procedures, confocal microscopy, dry eye syndrome after vitrectomy, intraocular surgery

Yiqing Li,1,2 Yan Wang,2,&ast; Meimei Chen,2,&ast; Ruixuan Jiang,2,&ast; Yi Ju2 1Department of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Ju, Email juyi1226@163.comPurpose: The aim of this study was to assess abnormal eye movement signs during different periods, namely, ictal periods and symptom-free intervals, in patients with vestibular migraine.Patients and Methods: We assessed oculomotor signs using videonystagmography in 90 patients with VM (40 during ictal periods and 50 during symptom-free intervals) according to validated diagnostic criteria.Results: Abnormal saccades, smooth pursuit and optokinetic test results; spontaneous nystagmus; and positional nystagmus were all observed in vestibular migraine patients, and there was no significant difference between different periods. Positional nystagmus was the most common in both the ictal and asymptomatic periods (60% and 36%, respectively). Positional nystagmus was induced in a variety of positions during both periods, and the slow-phase velocity ranged from < 2 to 10°/s. The duration of positional nystagmus was over 60s in most cases. Overall, central oculomotor dysfunctions occurred in 27.5% of patients during VM attacks and 4% of patients during symptom-free intervals; this difference was statistically significant (p = 0.002).Conclusion: In patients with VM, abnormal oculomotor signs can be found during both vertigo attacks and asymptomatic intervals. Positional nystagmus is the most common of these abnormalities and can be induced in different positions. The amplitude of these patients’ positional nystagmus tends to be low, and the duration tends to be long. Observing changes in eye movements by videonystagmography may be helpful in the diagnosis of VM.Keywords: vestibular migraine, eye movements, periods, videonystagmography, positional nystagmus

Feng Hu,1,2,&ast; Zilu Qu,1,2,&ast; Kai Chen,1,2 Ping Zhang,1 Bei Wang,1 Ruili Jiang,1 Yuyue Zuo,1 Ping Xia,1,&ast; Hongxiang Chen3,4,&ast; 1Department of Dermatology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Province & Key Laboratory of Skin Infection and Immunity, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Dermatology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, People’s Republic of China; 4Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongxiang Chen, Huazhong University of Science and Technology Union Shenzhen Hospital, No. 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, People’s Republic of China, Tel +86 13871022932, Email hongxiangchen@hotmail.com Ping Xia, Email alicexiaping@gmail.comIntroduction: As a mediator of inflammation resolution, lipoxin A4 (LXA4) mainly plays an anti-inflammatory role and promotes inflammation resolution. LXA4 plays an inhibiting inflammatory role in a variety of diseases, tissues and cells, including keratinocytes. Psoriasis is a chronic inflammatory skin disease mediated by dysregulation of inflammation of immune cells and keratinocytes. However, the expression and role of LXA4 in psoriasis-like mouse models are still unclear.Methods: Imiquimod (IMQ) topical treatment of dorsal skin induces psoriasis-like dermatitis in BALB/c mice, pretreated intraperitoneally with or without LXA4 prior to IMQ application. Severity of dorsal lesions is assessed by using a modified human scoring system and histopathology. The concentration of LXA4 and the expression of ALOX15 (a key gene in LXA4 metabolic synthesis) in lesional skins were detected by ELISA and Western blot. Quantitative PCR and ELISA were conducted to detect the mRNA and secretion levels of inflammatory cytokines. The proportion of IL-17A-producing γδT cells in skin and skin draining cervical lymph nodes and helper (Th) 17 cells in spleens was evaluated by flow cytometry. Western blotting was used to analyze the expressions of p-STAT3 and TRAF6.Results: The concentration of LXA4 and the expression of ALOX15 were decreased in IMQ-induced lesional skin. LXA4 significantly relieved psoriasis-like lesions in IMQ-induced mouse models. Furthermore, LXA4 decreased IMQ-induced systemic inflammation, including reduced the proportion of IL-17A-producing gdT cells in skin and skin draining cervical lymph nodes and Th17 cells in spleens, the secretion and expression of CCL20, IL-17A, IL-1β, and TNF-α in skin and serum. LXA4 markedly inhibited IMQ-induced expression of TRAF6 and p-STAT3.Conclusion: LXA4 significantly ameliorates IMQ-induced psoriasis-like inflammation, and LXA4 can be used as a target for psoriasis treatment.Keywords: lipoxin A4, psoriasiform dermatitis, imiquimod, γδT cells, Th17, inflammation

Xiaoling Liu, Ermei Zhong, Jinzhi Li, Chunxia Huang, Weixin Liu, Liping Zeng, Ge Song, Ronghua Jiang, Yu Liu NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou, 510600, People’s Republic of ChinaCorrespondence: Ge Song, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), No. 17 Mei Dong Road, Guangzhou, 510600, People’s Republic of China, Tel/Fax +86-020-87301316, Email gzdhmjyd@163.comBackground: This study aimed to explore the current situation of anxiety and depression on day of transfer in couples receiving in vitro fertilization and embryo transfer (IVF-ET) with donor sperm and analyze its influencing factors.Methods: This study selected 187 IVF-ET administered couples who received donor sperm from our Hospital from August 2021 to July 2022. On the day of IVF-ET with donor sperm transplantation, patients were investigated with general data questionnaire, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) to analyze their anxiety and depression scores and their influencing factors.Results: Scores of anxiety and depression on the day of transplantation in patients receiving IVF-ET with donor sperm were 43.98± 6.80 and 46.03± 10.61 respectively, which were higher compared to levels of Chinese health norm (P< 0.05). The anxiety score of patients’ spouses was 41.23± 6.69 and depression score was 44.23± 11.65, which were higher compared to levels of Chinese health norm (P< 0.05). Score of anxiety and depression of women was significantly higher compared to those of their spouse (P< 0.05). Anxiety and depression scores of women in non-pregnant group were significantly higher compared to those in pregnant group (P< 0.05). Regression analysis showed that education level and annual family income were influencing factors of anxiety and depression scores of IVF-ET with donor sperm couples on the day of transfer, and number of eggs taken and transfer times were influencing factors of depression scores of IVF-ET with donor sperm patients on the day of transfer.Conclusion: Psychological state of couples receiving IVF-ET with donor sperm was significantly affected, especially in female side. Medical staff should focus on patients with low education level, low family income, and more times of transfer and egg retrieval, and take targeted intervention measures to keep them in good psychological state, which is conducive to improving pregnancy outcome.Keywords: in vitro fertilization and embryo transfer with donor sperm, day of transfer, anxiety, depression, psychological state

Ruobing Jiang,1,&ast; Xin Ta,1,&ast; Min Xu,2 Zhihua Luo,3 Yijun Du,4 Xing Zhong,4 Tianrong Pan,4 Xiujing Cao1 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Endocrinology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Pediatrics, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Endocrinology, Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiujing Cao, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email xiujing.cao@ahmu.edu.cn Tianrong Pan, Department of Endocrinology, Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email ptr1968@163.comObjective: To investigate the current status of diabetes self-care behavior and the association between depression, self-efficacy and self-care in a sample of Chinese elderly type 2 diabetes mellitus (T2DM) patients.Methods: A cross-sectional study with a convenient sample including 240 elderly T2DM patients collected the data of demographic characteristics, diabetes self-care behavior, self-efficacy and depression status. The difference of self-care behavior in different sample characteristics was compared by independent t-test. The Personal correlation analysis was employed to examine the correlation of study variables. The method of bootstrap was used to analyze mediating role of depression.Results: Only 22.5% of patients reported better diabetes self-care behavior and depression partly mediated the association between self-efficacy and self-care behavior. The significant coefficient of path a (B = − 0.052, p < 0.001) and path b (B = − 0.423, p < 0.05) indicated negative associations of self-efficacy on depression, and depression on self-care behavior. The indirect effect (Path a × b) between self-efficacy and self-care behavior through depression was significant (B = 0.022, p < 0.05), the 95% bias-corrected bootstrap confidence interval was 0.004 to 0.006. Meanwhile, the mediating role of depression was not found significant among the participants reported 60– 74 years old (B = 0.104, p < 0.001). But depression completely mediated this association among the participants reported 75– 89 years old (B = 0.034, p > 0.05).Conclusion: The level of diabetes self-care behavior among the elderly T2DM patients in Dahu community of Anqing city was hardly optimistic. The self-efficacy focused intervention could be encouraged for community and clinicians to improve diabetes self-care behavior. Moreover, the prevalence of depression and T2DM is increasing in younger population. More work is needed to confirm these findings, especially conducting cohort studies on different populations.Keywords: diabetes self-care behavior, the elderly, type 2 diabetes mellitus, diabetes management self-efficacy, depression

Yulan Chang,1 Shujie Guo,2 Binbin Yuan,3 Huiling Chen,4 Ruxin Jiang5 1Department of Nursing, Henan Vocational College of Nursing, Anyang, Henan, 455001, People’s Republic of China; 2Department of Outpatient, Henan Provincial People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 3Department of Cardiovascular Surgery, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 4Department of Structural Heart Disease, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 5Department of Anesthesia and Perioperative Medicine, Henan Provincial People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of ChinaCorrespondence: Shujie Guo, Department of Outpatient, Henan Provincial People’s Hospital, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86 18538298287, Email guosj2022@yeah.netPurpose: The purpose of this study is to understand the risk perception, risk emotions and humanistic care needs of nursing staff during the Novel Coronavirus 2019 (Covid-19) pandemic.Methods: A cross-sectional survey was conducted on the perceived risk, risk emotions and humanistic care needs of 35,068 nurses in 18 cities of the Henan Province, China.We collected a total of 35,188 questionnaires, of which 35,068 were effectively returned, with an effective return rate of 99.7%. The collected data were summarized and statistically analyzed using Excel 97 2003 and IBM SPSS software.Results: Nurses’ risk perceptions and emotions vary during the covid-19 pandemic. In order to provide nurses with targeted psychological intervention to prevent nurses from suffering from unhealthy mental states.The results show that the total score of the nurses’ risk perceptions of Covid-19 was 3.66 ± 0.39, the highest score of nurses’ risk perception part is 5 points, and ≥ 3 points represent high risk and 88.3% of nurses believed that the Covid-19 risk was high. There were significant differences in the nurses’ total perceived risk scores for Covid-19 based on gender, age, prior contact with patients with suspected or confirmed Covid-19 and previous participation in other similar public health emergencies (P < 0.050). Of the nurses included in the study, 44.8% had some level of fear relating to Covid-19 and 35.7% were able to remain calm and objective. There were significant differences in the total scores for risk emotions relating to Covid-19 based on gender, age and prior contact with patients with suspected or confirmed Covid-19 (P < 0.050). Of the nurses included in the study, 84.8% were willing to receive humanistic care and 77.6% of these expected to be provided with humanistic care by institutions in the healthcare sector.Conclusion: Nurses with different basic data have different risk cognition and risk emotions. Different psychological needs should be considered, and targeted multi-sectoral psychological intervention services should be provided to help prevent nurses from developing unhealthy psychological states.Keywords: Covid-19, public health emergencies, risk perception, risk emotion, humanistic care

Hui Zhang,1,&ast; Guizhao Yang,1,&ast; Rongqiong Jiang,1 Dan Feng,1 Yuqin Li,1 Yong Chen,2 Guohua Yuan1 1Institute of Rheumatism and Immunology, the Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of China; 2Department of Rheumatism and Immunology, the People’s Hospital of Jianyang City, Jianyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohua Yuan, Institute of Rheumatism and Immunology, the Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China, Tel +8615983777907, Fax +8608172262301, Email ghyuan1981@139.comPurpose: Rheumatoid arthritis (RA) is a systemic inflammatory disorder with unknown etiology. Oxidative stress and immune imbalance play a critical role in the pathogenesis of rheumatoid arthritis. Bilirubin has recently been recognized as a potent antioxidant as well as an immunomodulatory agent of physiological importance. The aim of this study was to explore whether increased bilirubin concentrations are correlated with good clinical prognosis of rheumatoid arthritis.Patients and Methods: In this cross-sectional study, we included 197 healthy individuals and 197 RA patients in the Affiliated Hospital of North Sichuan Medical College from October 2020 to February 2022. The latter were classified into three classes of disease activity according to DAS28-ESR: remission and low (DAS28-ESR< 3.2), moderate (3.2≤DAS28-ESR≤ 5.1), and high (DAS28ESR> 5.1). Based on the clinical and laboratory data, we evaluated the association of bilirubin levels with disease activity in RA using multivariable ordered logistic regression.Results: The levels of total bilirubin and total bilirubin/albumin ratio were significantly lower (P < 0.001; P < 0.001) in RA patients compared with healthy controls. In RA patients, Spearman’s rank correlation analysis revealed that bilirubin and total bilirubin/albumin ratio were negatively correlated with disease activity and inflammatory marker (C-reactive protein, erythrocyte sedimentation rate, Interleukin-6). In multivariable ordered logistic regression, higher total bilirubin (OR=0.77, 95% CI: 0.67– 0.89, p< 0.001) independently predicted lower disease activity.Conclusion: Bilirubin levels remain associated with a reduction of disease activity, suggesting that bilirubin may be a protective factor for RA aggravation.Keywords: rheumatoid arthritis, bilirubin, bilirubin/albumin ratio, diagnostic marker, multivariate analysis

Ru Zhang,1,&ast; Qing Guan,1,&ast; Mengting Zhang,1 Yajie Ding,1 Zongzhe Tang,1 Hongliang Wang,2 Wei Zhang,3 Yue Chen,1 Rong Jiang,1 Yan Cui,1 Jie Wang1 1School of Nursing, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of General Practice, Community Health Service Center, Nanjing, People’s Republic of China; 3Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Wang; Yan Cui, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, People’s Republic of China, Tel +86-25-86869557, Email wangjienjmu@126.com; cyan_njmu@163.comObjective: Insulin resistance (IR) is a major factor involved in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). Triglyceride-glucose (TyG) index, an easily detected surrogate marker of IR, has not been explored sufficiently on its relationship with incident MAFLD risk. This study sought to investigate the association of baseline TyG index with the risk of MAFLD in a Chinese cohort.Methods: This health check-up cohort was constructed with eligible 2056 Chinese from a community. The TyG index was calculated as ln (fasting triglyceride [mg/dL]×fasting glucose [mg/dL]/2). Cox proportion hazard models were used to evaluate the longitudinal association between baseline TyG index and the risk of MAFLD.Results: During an average follow-up of 2.5 ± 0.5 years, about 12.8% of the subjects developed MAFLD, and the incidence of MAFLD trended to increase with the quartile TyG index (Ptrend < 0.05). After adjusting for all confounders, TyG index was independently correlated with the risk of incident MAFLD (HR = 1.784, 95% CI = 1.383– 2.302, P < 0.001), and the risk of MAFLD in the highest quartile of TyG index was two times higher than that in the lowest quartile (95% CI = 1.377– 2.992, P = 0.001). The restricted cubic spline analysis showed that the relationship between TyG index and the risk of MAFLD was linear in males (P for total < 0.001; P for non-linearity = 0.746), but nonlinear in females (P for non-linearity = 0.040).Conclusion: A high baseline TyG index was independently associated with a high risk of incident MAFLD, and we might develop the strategy of MAFLD prevention based on the TyG index.Keywords: triglyceride-glucose index, metabolic dysfunction-associated fatty liver disease, insulin resistance, risk, cohort study

Jinjin Wang,1,2,&ast; Liheng Bian,1,2,&ast; Anxin Wang,1,2 Xiaoli Zhang,1,2 Dandan Wang,1,2 Ruixuan Jiang,1,2 Wenjuan Wang,1,2 Yi Ju,1,2 Jingjing Lu,1,2 Xingquan Zhao1– 4 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingquan Zhao; Jingjing Lu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Email zxq@vip.163.com; lujingjing666@gmail.comBackground: Recent studies have reported the predictive value of liver fibrosis indices for hematoma enlargement in patients with intracerebral hemorrhage (ICH). However, little is known about the precise association between fibrosis and ICH prognosis. Thus, our study was designed to investigate the relevance of liver fibrosis, as evaluated by fibrosis-4 (FIB-4) score and poor outcomes after ICH.Methods: We used data from a prospective, multi-center and registry-based database. In this study, patients were stratified by the higher cut-off value of a FIB-4 score ≥ 2.67. The two groups of patients were then compared with regard to baseline characteristics, ICH severity and follow-up outcomes. We performed univariable and multivariable logistic regression analysis to determine the prognostic value of a FIB-4 score ≥ 2.67 for major disability or death. Kaplan–Meier survival curves were used to analyze the association between different FIB-4 scores and survival rate.Results: Our present study included 839 patients from 13 hospitals in Beijing. Participants with FIB-4 scores ≥ 2.67 had a larger baseline hematoma volume and a higher score on the modified Rankin Scale at follow-up (all p values < 0.05). In the logistic regression analysis, liver fibrosis defined by a FIB-4 score ≥ 2.67 was independently associated with poor clinical outcomes at discharge and at 1 year (at discharge: adjusted odds ratio [95% CI] = 1.894 [1.120– 3.202], p = 0.0172; at 1 year: adjusted odds ratio [95% CI] = 1.694 [1.021– 2.809], p = 0.0412). However, this association was not observed at 3 months. During the follow-up period, patients with a FIB-4 score ≥ 2.67 also had a significantly lower survival rate according to Kaplan–Meier survival analysis.Conclusion: Our study suggests that liver fibrosis defined by a FIB-4 score ≥ 2.67 is associated with poor clinical outcomes and lower survival rates in patients with mild to moderate ICH. These data provide reliable evidence for detecting fibrosis and managing related risk factors to improve prognosis after ICH.Keywords: liver fibrosis, FIB-4 score, intracerebral hemorrhage, clinical outcomes, survival rate

Yunzhu Wu,1 Fei Xie,2 Ruichen Jiang1 1School of Teacher Education, Anqing Normal University, Anqing, 246133, People’s Republic of China; 2School of Foreign Languages, Anqing Normal University, Anqing, 246133, People’s Republic of ChinaCorrespondence: Ruichen Jiang, School of Teacher Education, Anqing Normal University, Anqing, 246133, People’s Republic of China, Email 1811516004@sus.edu.cnPurpose: The novel coronavirus disease 2019 (COVID-19) pandemic has become a challenge for adolescents in China. This study aimed to explore the relationship between academic anxiety and self-esteem in Chinese candidates preparing for the college entrance examination during the COVID-19 pandemic and to examine the mechanism of mediating effect of self-regulated learning ability.Methods: A cross-sectional study was conducted among 293 college entrance examination candidates (including 170 females) from two middle schools in China using a voluntary, web-based, and anonymous questionnaire implemented via the Questionnaire Star app during COVID-19 prevalence in 2020.Results: This study found that 1) students in the high and low academic anxiety groups had different levels of self-regulated learning ability and self-esteem, 2) the academic anxiety, self-regulated learning ability, and self-esteem levels of students were significantly correlated and 3) after controlling the two independent variables of gender and subject type, academic anxiety had a significant negative predictive effect on self-esteem, and self-regulated learning ability played a mediating role between academic anxiety and self-esteem, where the mediating effect was 18.6%.Conclusion: Based on the observations of the present study, self-regulated learning capacity was a mediator between academic anxiety and self-esteem. These findings suggest an underlying process by which low academic anxiety may increase self-esteem in candidates preparing for the college entrance examination by increasing self-regulated learning ability.Keywords: academic anxiety, self-esteem, self-regulated learning ability

Cai Wen,1– 3 Rong Jiang,4 Zhiqiang Zhang,4 Bo Lei,4 Yingquan Zhong,4 Huangjun Zhou1,3 1Department of Oral Implantology, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of VIP Dental Service, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Orofacial Reconstruction and Regeneration Laboratory,The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Department of Dentistry, People’s Hospital of Aba Tibetan and Qiang Autonomous Prefecture, Ma’erkang, Sichuan, People’s Republic of ChinaCorrespondence: Cai Wen, Department of Oral Implantology, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Email wencai@swmu.edu.cnPurpose: Abutment access hole on dental implant crowns may facilitate crown retrieval and reduce cement overflow but present esthetic obstacle for patients. This study aimed to investigate the esthetic evaluation and acceptability of implant crowns with different hole designs from the perspective of patients and dentists.Materials and Methods: Anterior and posterior implant zirconia crowns were fabricated into three types: no hole (NH), 1 mm micro hole (MH), and 2.5 mm regular hole (RH). The NH crown was set as the control, and the anterior and posterior crowns with MH and RH were evaluated. The subjects, who were recruited randomly, were comprised of lay patients (n=60) and professional dentists (n=30). All subjects were invited to evaluate the esthetic performance of MH and RH crowns on a Visual Analog Scale (VAS), rate them from 0 to 10, state their acceptability of these crowns, and label them as acceptable and unacceptable.Results: The ANOVA analysis of the VAS esthetic evaluation showed that the size of the hole, the position of the teeth, and the professional background of the subject significantly and independently affected esthetic perception. Crowns with MH in the posterior position had higher esthetic scores and acceptability compared with crowns with RH in the anterior position, and dentists tended to show higher acceptance and better esthetic rating for crowns with holes compared with lay patients.Conclusion: The hypothesis that patients and dentists hold similar esthetic evaluations or acceptability towards implant crown hole designs was rejected. Lay patients had a lower tolerance for venting holes than dentists. Crowns with 1 mm micro holes were more recommendable than crowns with regular abutment access holes from the point of view of satisfying patients’ esthetic needs.Keywords: implant crown hole, visual analog scale, esthetic adherence, abutment access hole

Meng-Chang Yang,1,&ast; Peng Li,1,&ast; Wen-Jie Su,1 Rong Jiang,1 Jia Deng,1 Ru-Rong Wang,2 Chao-Li Huang3 1Department of Anesthesiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Internal Medicine, Eastern Hospital, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ru-Rong WangDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaTel +86 18140049936Fax +86 28-87393632Email wangrurong@scu.edu.cnChao-Li HuangDepartment of Internal Medicine, Eastern Hospital, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 585, Damian, Honghe North Road, Longquanyi District, Chengdu, People’s Republic of ChinaTel +86 13350855681Fax +86 28-87775681Email chaoli_huang@126.comPurpose: Several randomized clinical trials (RCTs) investigated the effects of the manual placental removal on hemorrhage or other hemorrhage-related complications compared with the spontaneous placental removal during cesarean section (CS), while the results remained controversial and were inconsistent. The purpose of this meta-analysis was to quantify the pooled effects of the methods of placental removal on hemorrhage during CS.Patients and Methods: A systematic literature search was conducted using PubMed, EMBASE, Web of Science, and Google Scholar. Heterogeneity was tested by I2 statistics and Q-statistic. The random-effects model or fixed-effects model were used to calculate the pooled effect for the included studies according to heterogeneity. And the term of standardized mean difference (SMD) with 95% confidence intervals (CI) was pooled and estimated the effects across all studies.Results: A total of nine RCTs were included in this meta-analysis. Compared with spontaneous group, manual placental removal increased the amount of hemorrhage (SMD = 0.53, 95% CI [0.12, 0.94]; Z = 2.54, P = 0.011) and increased the risk of endometritis (OR = 1.84, 95% CI [1.31, 2.58]; Z = 3.52, P < 0.0001). In contrast, there was no significant difference concerning the operating time (SMD = − 0.30, 95% CI [− 0.85, 0.24]; Z = 1.09, P = 0.276), the length of hospital stays (SMD = 0.11, 95% CI [− 0.08, 0.30]; Z = 1.11, P = 0.265), and blood transfusion requirement (OR = 1.36, 95% CI [0.91, 2.04]; Z = 1.52, P = 0.129), respectively.Conclusion: Comparing with spontaneous placental removal, manual placental removal appeared to be less positive effect during CS. Because of the limitations of this meta-analysis, more high-quality RCTs are needed to confirm our findings.Keywords: cesarean section, manual placental removal, spontaneous placenta removal, hemorrhage, meta-analysis

Yin Tang,1,2,&ast; Yu Cui,3– 5,&ast; Lin-lin Li,6,&ast; Ya-ping Guan,3– 5 Dong-feng Feng,3– 5 Bei-bei Yin,3– 5 Xue-feng Liang,2 Jing Yin,2 Rui Jiang,6 Jing Liang,3– 5 Ya-hong Sun,2 Jun Wang3– 5 1Postgraduate Department, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 2Department of Oncology, The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan, 250031, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, People’s Republic of China; 4Shandong Lung Cancer Institute, Jinan, 250014, People’s Republic of China; 5Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, 250014, People’s Republic of China; 6Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ya-hong SunDepartment of Oncology, The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), No. 38, Wu Yingshan Road, Tianqiao District, Jinan, 250031, People’s Republic of ChinaTel +86-531-58628551Email sunyahong@sdfmu.edu.cnJun WangDepartment of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Lixia District, Jinan, 250014, People’s Republic of ChinaTel +86-531-89268839Email ggjun2005@126.comPurpose: To evaluate the dynamics of early serum tumour markers (STMs) and the neutrophil-to-lymphocyte ratio (NLR) to predict clinical efficacy and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who received programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors.Patients and Methods: We retrospectively reviewed patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors between September 2017 and August 2020. NLR and STMs were routinely measured between immunotherapy initiation and the first radiological evaluation. A combination score based on the leading STM and NLR and their dynamic changes was established. The effects of leading STM change, NLR change, and the combination score on the objective response rate (ORR), durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS) were analysed. The accuracy of the combination score was evaluated by receiver operating characteristic (ROC) curve and the area under the curve (AUC).Results: Overall, 124 patients were included in this retrospective cohort study. The ORR was 22.8%, DCB was 54.5%, and the median OS and PFS were 21.6 and 14.9 months, respectively. Patients with low combination scores had a significantly improved ORR and DCB compared with those with intermediate or high scores (P = 0.002 for ORR, P < 0.0001 for DCB). In a multivariate model, the combination score was an independent indicator of PFS (P < 0.0001) and OS (P < 0.0001). The AUC demonstrated that the combination score (AUC = 0.706) has greater predictive power than either the posttreatment NLR (AUC = 0.668) or the leading STM change (AUC = 0.648) alone.Conclusion: An easy, cost-effective, and novel combination score based on the dynamics of an early STM and the NLR can accurately predict the clinical efficacy of PD-1/PD-L1 inhibitors and prognosis in advanced NSCLC patients.Keywords: serum tumour marker, neutrophil-to-lymphocyte ratio, PD-1 inhibitors, non-small-cell lung cancer, prognosis

Guilherme S Lopes,1,2 Suzette J Bielinski,2 Ann M Moyer,3 John Logan Black III,3 Debra J Jacobson,1 Ruoxiang Jiang,1 Nicholas B Larson,1 Jennifer L St Sauver2 1Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 2Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 3Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USACorrespondence: Guilherme S LopesDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USATel +1 507 422 6094Email lopes.guilherme@mayo.eduBackground: Several small studies have previously investigated associations between the cytochrome P450 2D6 (CYP2D6) metabolism and response to opioids. We used a large sample of patients to study associations between CYP2D6 phenotypes and estimated CYP2D6 enzymatic activity scores with pain control and adverse reactions related to codeine and tramadol use. We conducted additional analyses to determine whether our results were consistent among men and women.Methods: We used data from 2,877 participants in the RIGHT Protocol who were prescribed codeine and/or tramadol between 01/01/2005 and 12/31/2017 and who were not prescribed CYP2D6 inhibitors within 1 year prior to the opioid prescription. CYP2D6 phenotype categories were condensed into four groups: (1) Ultra-rapid and Rapid (n = 61), (2) Normal and Intermediate to Normal (n = 1,448), (3) Intermediate and Intermediate to Poor (n = 1,175), and (4) Poor metabolizer status (n = 193). Opioid-related outcomes included indications of poor pain control or adverse reactions related to medication use. We modeled the risk of each outcome using logistic regression, adjusting for age, sex, race, and ethnicity.Results: The results revealed a trend from poor to ultra-rapid and rapid CYP2D6 phenotypes in which the risk of adverse reactions incrementally increased and the risk of poor pain control incrementally decreased. This trend reached statistical significance among female (but not male) participants. Among normal and intermediate to normal metabolizers, a larger proportion of women experienced adverse reactions relative to men.Discussion: We replicated and extended the findings of previous research indicating associations between CYP2D6 phenotypes and response to opioids. In addition, the observed associations were stronger in women than in men. We recommend sex differences to be factored in future research investigating associations between pharmacogenomics and response to medications.Keywords: opioids, codeine, tramadol, pharmacogenomics, sex differences, CYP2D6

Shuang Lin,1,2 Lei Tang,1 Ranhua Jiang,3 Yu Chen,1 Sheng Yang,1 Ling Li,1 Ping Li1 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Cardiology, Zhongyi Northeast International Hospital, Shenyang, Liaoning Province, People’s Republic of China; 3Department of Endocrinology, Liaoyang Diabetes Hospital, Liaoyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Ping LiDepartment of Endocrinology, Shengjing Hospital of China Medical University, No.39, Huaxiang Road, Tiexi District, Shenyang 110022, Liaoning Province, People’s Republic of ChinaTel +86 18940255673Email scizhong@163.comLing LiDepartment of Endocrinology, Shengjing Hospital of China Medical University, No.36, Sanhao Street, Heping District, Shenyang 110004, Liaoning Province, People’s Republic of ChinaTel +86 18940251181Fax +86 02425944460Email liling8864@hotmail.comAim: To investigate the relationship of the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT) and metabolic syndrome (MetS) in adolescents in northeast China.Methods: A stratified cluster random sample of 935 students 11–16 years of age in a city in the northeast of China were enrolled in 2010–2011. Participants were given a physical examination and a laboratory evaluation, and 93 participants were followed-up after 5 years.Results: AST/ALT was negatively correlated with waist circumference (WC), waist-to-hip ratio, body mass index (BMI), diastolic blood pressure, triglycerides, low-density lipoprotein, uric acid, fasting insulin, and insulin resistance. It was positively correlated with high-density lipoprotein. Multivariate logistic regression showed that the risk of MetS was 6.02 times greater in adolescents with the lowest, compared with the highest, AST/ALT. Central obesity was the MetS component most closely associated with low AST/ALT [odds ratio (OR) =5.13, 95% CI: 2.83, 9.28]. Five years later, baseline AST/ALT was negatively correlated with WC (r=−0.21, P=0.046), BMI (r=−0.29, P=0.005) and fasting plasma glucose (r=−0.25, P=0.017).Conclusion: In adolescents, AST/ALT was significantly associated with MetS and its components and predicted overweight/obesity in adulthood.Keywords: metabolic syndrome, aspartate aminotransferase, alanine aminotransferase, adolescents

Yuan Fang,1,* Hsiangyu Ku,1,* Dekang Gan,1,2 Rui Jiang,1 Xinghuai Sun1–5 1Department of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, People’s Republic of China; 2Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, People’s Republic of China; 3Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Fudan University, Shanghai 200031, People’s Republic of China; 4NHC Key Laboratory of Myopia, Fudan University, Shanghai 200031, People’s Republic of China; 5State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinghuai Sun; Rui JiangDepartment of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, 83 Fenyang Road, Shanghai 200031, People’s Republic of ChinaTel +86 21 64377134Email xhsun@shmu.edu.cn; 2jiang@163.comPurpose: To evaluate the efficacy and safety of travoprost 0.004% versus timolol 0.5% as an initial intraocular pressure (IOP)-lowering medication for ocular hypertension secondary to vitrectomy.Patients and methods: We performed a randomized, controlled, observer-blinded clinical trial in the Eye & ENT Hospital of Fudan University in China. This trial was registered at www.chictr.org.cn (ChICTR1800014942) before patient enrollment. Seventy-nine adults with IOP of 25–45 mmHg secondary to vitrectomy in the latest one month were enrolled and randomized to receive travoprost 0.004% or timolol 0.5%. More drugs were administered to patients with IOP > 25 mmHg during follow-up.Results: The mean IOP reduction at day 1 was −10.97 mmHg in the timolol group and −15.02 mmHg in the travoprost group (P = 0.006); no significant difference was observed between the groups at later time points. The number of IOP-lowering medications at day 21 was 0.64 in the timolol group and 1.15 in the travoprost group (P = 0.038), while no significant differences were observed at other time points. The proportion of single IOP-lowering medications used during the 4-week follow-up was 72.73% in the timolol group and 68.42% in the travoprost group (P = 0.692). Inflammation scores were not significantly different in the two groups at any time point. Increased ocular hyperemia occurred in 8 patients (19%) in the travoprost group and none in the timolol group (P = 0.005). There were no significant differences in other adverse events between the two groups. After logistic regression model analysis, IOP ≥ 30 mmHg, inflammation score ≥ 2, and silicone oil as tamponade were found to be the factors with significant effects on the number of IOP-lowering medications used during the 4-week follow-up.Conclusion: Travoprost and timolol have similar efficacy and safety for treating ocular hypertension secondary to vitrectomy.Keywords: travoprost, timolol, vitrectomy, ocular hypertension, early-onset

Katerina Zakka,1 Renjian Jiang,2 Olatunji B Alese,1 Walid L Shaib,1 Christina Wu,1 Joel P Wedd,3 Marty T Sellers,4 Madhusmita Behera1,2 Bassel F El-Rayes,1 Mehmet Akce11Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; 2Department of Research Informatics, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; 3Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; 4Division of General and GI Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USABackground: HCC variants are rare primary hepatic tumors. The aim of this study is to compare clinical characteristics and outcomes of HCC variants with pure HCC.Methods: Patients diagnosed between 2004 and 2013 with ICD-O-3 8180/3 and 8170/3-8175/3 were identified from the National Cancer Database. Univariate and multivariate survival analyses were conducted to analyze the association between histology and overall survival (OS).Results: 80,280 patients were identified; pure HCC 78,461 (97.7%), fibrolamellar (FLHCC) 310 (0.4%), scirrhous 161 (0.2%), spindle cell 72 (0.1%), clear cell 487 (0.6%), pleomorphic 23 (0.0%), and combined HCC and cholangiocarcinoma (mixed HCC) 766 (1.0%). 76.7% were male and 72% Caucasian. Liver transplant was performed in 10.1% of pure HCC, 14.5% of mixed HCC, 16.2% of scirrhous, 6.9% of spindle cell, 8.8% of clear cell, 8.7% of pleomorphic, and 3.2% of FLHCC (p

Yeqi Sun,1,* Wenwei Yu,1,* Wenbin Guan,1,* Lei Cai,1 Meng Qiao,1 Leizhen Zheng,2 Ruiqi Jiang,1 Ruifen Wang,1 Lifeng Wang11Department of Pathology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, People’s Republic of China; 2Department of Oncology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, People’s Republic of China*These authors contributed equally to this workPurpose: Targeting the PD-1/PD-L1 pathway has emerged as a novel therapy for cancer. To identify rational candidates for anti-PD-1/PD-L1 immunotherapy in gastric cancer (GC), the abundance of PD-L1 expression was evaluated on a kind of biomarker-based molecular classification for shaping prognosis and treatment planning.Methods: One hundred and sixty-five GCs were classified into five subgroups using immunohistochemistry (IHC) and in situ hybridization (ISH) methods, based on a panel of seven markers (MLH1, PMS2, MSH2, MSH6, E-cadherin, P53, and Epstein-Barr virus mRNA). The expression of PD-L1 in GC tissues was analyzed immunohistochemically.Results: The five categories (Epstein–Barr virus positivity, microsatellite instability, aberrant E-cadherin, aberrant P53 expression, and normal P53 expression) correspond to the reported molecular subgroups for similar proportions and clinicopathologic characteristics. Survival analysis indicated that subgroups with aberrant E-cadherin expression independently predicted a worse prognosis in GC patients (HR=2.51, P=0.010). The clinical and prognostic profiles produced by this stratification in nonintestinal-type GC were distinguishable from those in intestinal-type. Although PD-L1 was not a significant prognostic factor, that more frequent presence of PD-L1-positive in microsatellite instability tumors than other subtypes (P

Xue Wang,1 Chunyang Kang,2 Ying Pan,1 Rihua Jiang31Department of Obstetrics & Gynecology, China–Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Neurology, China–Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Dermatology, China–Japan Union Hospital of Jilin University, Changchun, People’s Republic of ChinaObjective: The study aimed to synthesize superparamagnetic NaYF4:Yb,Er@PE3@Fe3O4 upconversion nanoprobes and to study their photothermal effects for the treatment of malignant melanoma.Methods: Morphological characteristics of the synthesized nanoprobes were examined by scanning electron microscopy. Their biocompatibility and biodistribution profiles were assessed through blood routine/biochemistry tests and the inductively coupled plasma/optical emission spectrometry-based analysis of tissue metal elements. Their photothermal conversion efficiency and their potential as contrast agents for upconversion luminescence (UCL)/magnetic resonance imaging (MRI) dual-modal imaging were tested. Efficacy in photothermal therapy, which was achieved by combining nanoprobes with near-infrared (NIR) irradiation, was evaluated in both A375 cell line and BALB/c mice models. The underlying mechanisms were interrogated by molecular approaches including the MTT assay, flow cytometry, semiquantitative PCR, western blot, and immunohistochemistry.Results: 1) Our synthesized NaYF4:Yb,Er@PE3@Fe3O4 nanoprobes exhibited a uniform cubic morphology with a diameter of ∼50 nm. Subcutaneous administration led to no severe, long-lasting adverse effects in mice, possibly due to complete removal of these nanomaterials within one month. 2) Our nanoprobes possessed superior photothermal conversion efficiency and strong contrasting effects during UCL/MRI dual-modal imaging, corroborating their applications in imaging-guided photothermal therapy. 3) Combinatorial treatment of these nanoprobes with NIR irradiation induced profound apoptosis/necrosis in A375 cells. Similarly, the same treatment modality led to strong therapeutic effects in BALB/c mice implanted with A375 tumor xenografts. Mechanistic studies suggested an involvement of heat shock protein 70 in mediating the observed antitumor effects of our nanoprobes.Conclusion: Our study describes a convenient method to synthesize a new type of superparamagnetic upconversion nanoprobes, which possess high biocompatibility and can be used in imaging-guided photothermal therapy for the treatment of malignant melanoma. Importantly, our findings will promote clinical applications of NaYF4:Yb,Er@PE3@Fe3O4 as novel theranostic agents in treating melanoma and many other tumors.Keywords: upconversion nanoparticles, near infrared, photothermal therapy, melanoma, heat shock protein 70

Wei Shi,1,2 Rui Jiang,1,2 Fei Liang,3 Genhua Yu,4 Jiang Long,2,5 Jiandong Zhao1,21Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Shanghai, People’s Republic of China; 3Clinical Statistic Center, Shanghai Cancer Center and Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 4Department of Radiation Oncology, Zhebei Mingzhou Hospital, Huzhou City, Zhejiang Province, People’s Republic of China; 5Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of ChinaPurpose: The objective of this study was to analyze the safety and efficacy of definitive chemoradiotherapy and salvage chemotherapy in pancreatic cancer (PC) patients with isolated locoregional recurrence after radical resection and assess the factors associated with tumor response.Patients and methods: A retrospective study of isolated locoregional recurrent PC patients who were treated with definitive chemoradiotherapy and salvage chemotherapy at our institution between 2012 and 2017 was conducted. Medium dose of 56.0 Gy (range: 54.0 Gy - 60.2 Gy) in 1.8 Gy to 2.15 Gy daily fractions was prescribed to the PTV-G and 50.4 Gy was prescribed to the PTV-C. Patients received chemotherapy before, at the same time with or after radiotherapy. The overall survival (OS) and freedom from locoregional progression (FFLP) rates were estimated by the Kaplan–Meier method, and the log-rank test was performed to compare survival curves. The Cox regression was used to identify factors affecting response to treatment and survival.Results: Thirty-one patients were included. The median interval from the resection of primary PC to the diagnosis of the locoregional recurrence (DFI) was 7.4 months (range 0.2–44.6). Within a median follow-up from the start of radiotherapy (RT) of 31.7 months (95% CI: 20.0–43.5 months), the medium OS and FFLP rates from the start of RT were 23.6 and 12.0 months, respectively. DFI >6 months was shown to be a significant factor associated with favorable OS. Acute and late toxicity of grade 3 occurred in 3 patients (9.7%) and 1 patient (3.2%) respectively. No grade 4 toxicity or higher occurred.Conclusions: This single-institution retrospective analysis identified definitive chemoradiotherapy and salvage chemotherapy to be a feasible and tolerable treatment strategy for patients with isolated locoregional recurrence after radical resection of primary PC.Keywords: pancreatic cancer, isolated locoregional recurrence, locoregional oligo-recurrence, chemoradiotherapy, radiotherapy

Jixian Liu,1,* Zhimin Mu,1,* Li Liu,2 Kang Li,2 Richeng Jiang,3 Peng Chen,3 Qiang Zhou,4 Meiling Jin,5 Yuxiang Ma,6 Yuancai Xie,1 Jianxing Xiang,7 Bing Li,7 Yafeng Ma,7 Xinru Mao,7 Lu Zhang,7 Tengfei Zhang,7 Da Wu11Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen 518035, People’s Republic of China; 2Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410000, People’s Republic of China; 3Department of Thoracic Oncology, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300000, People’s Republic of China; 4Department of Oncology I, Yueyang First People‘s Hospital, Yueyang 414000, People’s Republic of China; 5Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200000, People’s Republic of China; 6Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510000, People’s Republic of China; 7Burning Rock Biotech, Guangzhou 510000, People’s Republic of China*These authors contributed equally to this workPurpose: EGFR and anaplastic lymphoma kinase (ALK) alterations have been regarded as oncogenic drivers and incorporated into clinical practices to manage nonsmall cell lung cancer (NSCLC). Alterations of these two genes were traditionally considered to be mutually exclusive, but recent studies have suggested that they can occur concomitantly. Here, we investigated the prevalence, clinical features and outcomes in response to the treatment of NSCLC patients who harbor EGFR and ALK co-alterations.Methods: We reviewed the genomic profiles of 419 ALK-rearranged NSCLC patients with the intent of investigating the EGFR kinase domain (exon 18–21) and ALK co-alterations. The genomes of these patients were sequenced in a Clinical Laboratory Improvement Amendments-certified laboratory.Results: The overall frequency of concomitant EGFR (exon 18–21) and ALK alterations was 5.01% (21/419) in ALK-rearranged NSCLC patients. The concomitant rate of EGFR alterations in patients with EML4-ALK co-alterations (3.06%, 11/359) was dramatically lower than that in patients with non-EML4-ALK co-alterations (16.67%, 10/60, p5.2 months).Conclusion: EML4-ALK/EGFR and non-EML4-ALK/EGFR co-alterations displayed distinct clinical features and responses to EGFR-TKIs, suggesting that non-EML4-ALK co-alterations are likely to occur as a resistance mechanism to EGFR-TKI. In addition, dual-TKI therapy might be a better choice than single-TKI treatments for these co-altered patients. To the best of our knowledge, this is the largest dual-positive EGFR/ALK cohort study in People’s Republic of China.Keywords: EGFR alteration, ALK rearrangement, nonsmall cell lung cancer, EML4-ALK, tyrosine kinase inhibitor

Shuang Xie,1,2 Ranhua Jiang,3 Wanfeng Xu,4 Yu Chen,4 Lei Tang,1 Ling Li,1 Ping Li4 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, P.R. China; 2Department of General Medicine (VIP ward), Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province, P.R. China; 3Department of Endocrinology, Liaoyang Diabetes Hospital, Liaoyang, Liaoning Province, P.R. China; 4Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, P.R. China Purpose: Free insulin-like growth factor-1 (IGF-1) ratio (the ratio of IGF-1/insulin-like growth factor binding protein-3 [IGFBP-3]) was shown to be negatively correlated with metabolic syndrome (MetS) in adults, but it was unknown in Chinese adolescents. Patients and methods: The cross-sectional study enrolled 701 healthy school students (aged 12–16 years, 46.1% females) and 93 of them (18–22 years old, 46.2% females) were followed after 5 years. Results: In the cross-sectional study, the IGF-1/IGFBP-3 ratios were found correlated with low-density lipoprotein cholesterol (LDL-C; r= -0.071, P18 years old. We found a lower baseline ratio of IGF-1/IGFBP-3 in adolescence was an independent risk factor for MetS in adulthood (OR=10.724, 95% CI: 1.032–11.403) and also indicated a higher body mass index (β=-1.361, 95% CI: -2.513 to -0.208) after 5 years. Conclusion: The lower IGF-1/IGFBP-3 ratio was an independent risk factor for MetS, hypertension, and high LDL-C in adolescents of northeast China and was also a predictive marker for MetS and increased body mass index in the adulthood. Keywords: IGF-1, IGFBP-3, adolescent, metabolic syndrome

Zhengzou Fang,1,* Rong Jiang,2,* Lirong Zhang,3,* Yunchao Wu,2 Xuefen Zhao,2 Lulu Zhao,2 Jiangang Li,4 Shengqiang Zou,1 Miaomiao Zhang,2 Fengyi Du1,2 1Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated Jiangsu University, 2School of Medicine, Jiangsu University, 3Department of Radiology, Affiliated Hospital of Jiangsu University, 4Tianyi Health Sciences Institute (Zhenjiang) Co., Ltd. Zhenjiang, People’s Republic of China *These authors contributed equally to this work Introduction: Although oral administration of Bifidobacterium is a promising approach for diseases, lack of resistance to harsh conditions and real-time tracking in gastrointestinal system in vivo are still major challenges in basic research and clinical applications. Materials and methods: In this study, we fabricated a chitosan-coated alginate microcapsule loaded with in situ synthesized barium sulfate (CA/BaSO4 microcapsule) for oral Bifidobacterium delivery and real-time X-ray computed tomography (CT) imaging. CA/BaSO4 microcapsules containing the Bifidobacterium were prepared in situ by one-step electrostatic spraying method, and then coated with chitosan. Results: The results indicated that CA/BaSO4 microcapsules with an average diameter of approximately 200 µm possessed favorable mechanical stability and X-ray attenuation capacity. Encapsulation of Bifidobacteria in the CA/BaSO4 microcapsules exhibited superior resistance to cryopreservation and gastric acid environment in vitro. After oral administration in mice, these CA/BaSO4 microcapsules could be real-time visualized by CT imaging and readily reached the intestine to release Bifidobacteria. Conclusion: The radiopaque CA/BaSO4 microcapsules provide a novel platform for efficient protection, non-invasive real-time monitoring and intestinal-targeted Bifidobacterium delivery. Keywords: alginate, microcapsule, CT imaging, intestinal-targeted, Bifidobacterium

Jinghui Sun,1 Shu Jing,2 Rui Jiang,3 Chunmei Wang,1 Chengyi Zhang,1 Jianguang Chen,1 He Li1 1Department of Pharmacology, College of Pharmacy, Beihua University, Jilin, People’s Republic of China; 2General Surgery Area, Affiliated Hospital of Beihua University, Jilin, People’s Republic of China; 3Jilin Technology Innovation Center for Chinese Medicine Biotechnology, College of Chemistry and Biology, Beihua University, Jilin, People’s Republic of China Objective: The aim of this study was to evaluate the antiaging effect of Schisandra chinensis lignans (SCL) by analyzing the characteristics in the serum of d-galactose (d-gal)-induced rats.Methods: Forty male Wistar rats were randomly divided into control group, d-gal model group, low-dose SCL group (50 mg/kg/d), medium-dose SCL group (100 mg/kg/d), and high-dose SCL group (200 mg/kg/d). A serum metabolomics analysis method based on rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry was carried out to study the characteristics of d-gal-induced aging rats and evaluate the antiaging effects of SCL, and multivariate statistical analysis was performed for pattern recognition and characteristic metabolites identification. The relative levels of p19, p53, and p21 genes in the brain tissue were measured by quantitative real-time polymerase chain reaction for investigating the underlying mechanism. Results: Metabolomics analysis showed that 15 biomarkers were identified and 13 of them recovered to the normal levels after the administration of SCL. Based on the pathway analysis, the antiaging mechanisms of SCL might be involved in the following metabolic pathways: energy, amino acid, lipid, and phospholipid metabolism. Furthermore, SCL significantly inhibited the mRNA expression level of p19, p53, and p21 in the brain of aging rats induced by d-gal. Conclusion: These results suggest that SCL can delay rat aging induced by d-gal through multiple pathways. Keywords: Schisandra chinensis lignans, aging, rat, metabolomics, RRLC-Q-TOF-MS, RT-PCR

Haishen Kong,1,2 Lingmei Fang,3 Rujin Jiang,4 Jixiang Tong2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; 2Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; 3Clinical Laboratory, Chunan First People’s Hospital, Zhejiang Province People’s Hospital Chunan Branch, Hangzhou, China; 4Clinical Laboratory, Yuhang Hospital of Traditional Chinese Medicine, Hangzhou, China Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen. Various virulence and antiseptic-resistant factors increase the pathogenicity of MRSA strains and allow for increased infection rates.Purpose: The purpose of this study was to investigate the prevalence and distribution of virulence-associated and antiseptic-resistant genes from epidemic MRSA strains isolated from East China.Methods: A newly designed multiplex PCR assay was used to assess whether the virulence-associated genes sasX and pvl and the chlorhexidine tolerance gene qacA/B were present in 189 clinical isolates of MRSA. Multilocus sequence typing (MLST) and Staphylococcal protein A (spa) typing of these isolates were also performed. The frequency of these genes in isolates with epidemic sequence types (STs) was investigated. Results: Twenty STs and 36 spa types with five epidemic clones (ST5-t311, ST59-t437, ST5-t002, ST239-t030, and ST239-t037) were identified. The prevalence of sasX, pvl, and qacA/B in all isolates was 5.8%, 10.1%, and 20.1%, respectively. The prevalences of these genes in isolates with ST5, ST59, ST239, and other ST genetic backgrounds were all significantly different (P

Tian-Xiang Chen,1 Bigyan Pudasaini,1 Jian Guo,2 Su-Gang Gong,1 Rong Jiang,1 Lan Wang,1 Qin-Hua Zhao,1 Wen-Hui Wu,1 Ping Yuan,1 Jin-Ming Liu1 1Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China; 2Department of Pulmonary Function Test, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China Background: Sex differences in chronic thromboembolic pulmonary hypertension (CTEPH) have been revealed in few studies. Although right heart catheterization (RHC) is the gold standard for clinical diagnosis and assessment of prognosis in pulmonary hypertension (PH), cardiopulmonary exercise testing (CPET) has been a more widely used assessment of functional capacity, disease severity, prognosis, and treatment response in PH. We hypothesized that the “sex-specific” CPET indices could estimate the severity of inoperable CTEPH.Methods: Data were retrieved for 33 male (age, mean ± standard deviation [SD] =62.5±13.4 years) and 40 female (age, mean ± SD =56.3±11.8 years) patients with stable CTEPH who underwent both RHC and CPET at Shanghai Pulmonary Hospital from February 2010 to February 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the predictive value of CPET indices to hemodynamic parameters. Event-free survival was estimated using the Kaplan–Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the independent event-free survival predictors.Results: Numerous CPET parameters were different between male and female patients with CTEPH and the control group. There were no significant differences in both clinical variables and RHC parameters between male and female patients with CTEPH. O2 pulse, workload, minute ventilation (VE), and end-tidal partial pressure of O2 (PETO2) at anaerobic threshold, as well as peak O2 pulse, workload, VE, and nadir VE/CO2 were significantly higher in male patients than in female patients (P

Yuan Fang,1 Qingqing Long,1 Xiaoqian Wang,2 Rui Jiang,1 Xinghuai Sun1,3–5 1Department of Ophthalmology and Visual Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 2Department of Ophthalmology, Jiangyin Bright Eye Hospital, Jiangyin, Jiangsu, 3State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, 4Key Laboratory of Myopia, NHFPC (Fudan University), 5Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, People’s Republic of China Objective: The aim of this study was to investigate the incidence, risk factors, and treatment of elevated intraocular pressure (IOP) 1 year after vitrectomy in eyes without a history of glaucoma or ocular hypertension.Patients and methods: This retrospective study comprised 256 eyes from 256 consecutive patients without a history of glaucoma or ocular hypertension who underwent vitrectomy and were followed up for 1 year. The incidence of elevated IOP at 1 year after vitrectomy was calculated. We compared the characteristics of patients with or without elevated IOP to identify possible risk factors for elevated IOP. The treatments used to control IOP were recorded and analyzed.Results: A total of 50 patients (19.5%) had elevated IOP after vitrectomy at the 1-year follow-up. Tamponade was a significant risk factor for elevated IOP (P

Lan Wang,1,* Yuan-Zhe Jin,2,* Qin-Hua Zhao,1 Rong Jiang,1 Wen-hui Wu,1 Su-Gang Gong,1 Jing He,1 Jin-Ming Liu,1 Zhi-Cheng Jing1,3 1Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; 2Department of Cardiology, The Fourth Affiliated Hospital of China Medical University, Liaoning, China; 3Thrombosis and Vascular Medicine Center, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China *These authors contributed equally to this work Abstract: Studies have shown that vasodilators such as iloprost can be useful for treating pulmonary hypertension (PH). However, in patients with COPD, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange. The efficacy and safety of iloprost inhalation was assessed in 67 patients with PH associated with COPD (COPD-PH), diagnosed by right heart catheterization. Of these, 37 patients had severe PH (mean pulmonary arterial pressure [mPAP] >35 mmHg or mPAP 25–35 mmHg with low cardiac index [

Fengyi Du,1,2,* Jiaming Lou,1,* Rong Jiang,2,* Zhengzou Fang,2,* Xuefen Zhao,2 Yuanyuan Niu,2 Shenqiang Zou,3 Miaomiao Zhang,2 Aihua Gong,2 Chaoyang Wu1 1Department of Oncology, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, People’s Republic of China; 2Department of Cellular Biology, School of Medicine, Jiangsu University, Zhenjiang, People’s Republic of China; 3Department of Hepatosis, The Third Hospital of Zhenjiang Affiliated, Jiangsu University, Zhenjiang, People’s Republic of China *These authors contributed equally to this work Abstract: The inherent radioresistance and inaccuracy of localization of tumors weaken the clinical implementation effectiveness of radiotherapy. To overcome these limitations, hyaluronic acid-functionalized bismuth oxide nanoparticles (HA-Bi2O3 NPs) were synthesized by one-pot hydrothermal method for target-specific computed tomography (CT) imaging and radiosensitization of tumor. After functionalization with hyaluronic acid, the Bi2O3 NPs possessed favorable solubility in water and excellent biocompatibility and were uptaken specifically by cancer cells overexpressing CD44 receptors. The as-prepared HA-Bi2O3 NPs exhibited high X-ray attenuation efficiency and ideal radiosensitivity via synergizing X-rays to induce cell apoptosis and arrest the cell cycle in a dose-dependent manner in vitro. Remarkably, these properties offered excellent performance in active-targeting CT imaging and enhancement of radiosensitivity for inhibition of tumor growth. These findings demonstrated that HA-Bi2O3 NPs as theranostic agents exhibit great promise for CT imaging-guided radiotherapy in diagnosis and treatment of tumors. Keywords: HA-Bi2O3 NPs, CT imaging, radiosensitivity, HA, bismuth

Rong Jiang,1 Cheng Wu,2 Bigyan Pudasaini,1 Lan Wang,1 Qin-Hua Zhao,1 Rui Zhang,1 Wen-Hui Wu,1 Ping Yuan,1 Zhi-Cheng Jing,1 Jin-Ming Liu1 1Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 2Department of Health Statistics, Second Military Medical University, Shanghai, People’s Republic of China Background: Severe pulmonary hypertension (PH) resulting from a chronic lung disease (CLD) (severe CLD-PH) requires more aggressive treatment due to its increased mortality compared with mild PH. Therefore, we developed a Doppler echocardiography scoring index (ESI) to predict severe CLD-PH.Methods: A derivation cohort of 107 patients with CLD who underwent echocardiography was classified into two groups, the normal/mild PH group and the severe PH group, based on the right heart catheterization. Meanwhile, we designed the ESI by multivariate logistic regression to validate the predicted outcomes. The ESI was calculated using the following formula: ESI = ESIRVEDTD + ESIPASP + ESIPAd - ESITAPSE. Additionally, the ESI was weighted by +2 points for right ventricular end-diastolic transverse dimension ≥3.8 cm or pulmonary artery diameter ≥2.7 cm, +3 points for systolic pulmonary artery pressure (PASP) ≥61 mmHg, and -3 points for tricuspid annular plane systolic excursion ≥1.65 cm.Results: In the derivation cohort, PASP ≥61 mmHg estimated by echocardiography exhibited 80.4% sensitivity and 84.3% specificity with area under receiver-operating characteristic curve of 0.823 (95% CI: 0.797–0.942, P

Jian Yang,1,2,* Yang Yu,1,* Wei Liu,2 Zhi Li,2 Zhongqing Wei,2 Rongjiang Jiang1,2 1The Second Clinical Medical College of Nanjing Medical University, 2Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work. Abstract: Tau, a microtubule-associated protein, has been investigated primarily in neurons. Recently, tau has been explored to be associated with increased drug resistance in various kinds of cancers. We found that the tau was expressed in prostate cancer cell lines DU145 and PC-3. We also reported that recurrent prostate cancer cells after docetaxel treatment have higher levels of microtubule-associated protein tau. In vitro, inactivation of tau by gene knockdown suppressed cell proliferation and sensitized docetaxel cytotoxicity. Also, our results demonstrated that the PI3K/Akt/mTOR pathway was upregulated in DU145 docetaxel-resistant cells compared with the DU145-naïve cells. Thus, targeting tau protein and PI3K/Akt/mTOR pathway are promising strategies to enhance docetaxel response for the treatment of prostate cancer. Keywords: prostate cancer, microtubule-associated protein tau, docetaxel resistance, tau protein, PI3K/Akt/mTOR pathway

Xiaoping Li,1–3,* Chi Cai,3,* Rong Luo,4 Rongjian Jiang,1 Jie Zeng,1 Yijia Tang,1 Yang Chen,1 Michael Fu,5 Tao He,1 Wei Hua31Department of Cardiology, Hospital of the University of Electronic Science and Technology of China, Sichuan Provincial People’s Hospital, Chengdu, Sichuan, 2School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 3Department of Clinical Electrophysiology, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 4Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 5Department of Medicine, Sahlgrenska University Hospital/Östra Hospital, Gothenburg, Sweden*These authors contributed equally to this workObjective: Recent studies have shown that sex and age are associated with outcomes in patients with cardiomyopathy. The purpose of this study was to determine the all-cause mortality of dilated cardiomyopathy (DCM) by age and sex.Methods and results: The patients were divided into non-elderly (age

Jiangbo Hu,1,* Dilong Chen,2,* Rong Jiang,2 Qunyou Tan,3 Biyue Zhu,4 Jingqing Zhang11Medicine Engineering Research Center, Chongqing Medical University, Chongqing, People's Republic of China; 2Department of Histology and Embryology, Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, 3Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 4West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China *These authors contributed equally to this workPurpose: The purpose of this study was to assess the improved absorption and in vivo kinetic characteristics of a novel water-in-oil nanoemulsion containing evodiamine–phospholipid nanocomplex (NEEPN) when administered orally.Methods: NEEPN was fabricated by loading an evodiamine–phospholipid nanocomplex into a water-in-oil nanoemulsive system. The gastrointestinal absorption of NEEPN was investigated using an in situ perfusion method. The modified in vivo kinetic characteristics of evodiamine (EDA) in NEEPN were also evaluated.Results: Compared with EDA or conventional nanoemulsions containing EDA instead of evodiamine–phospholipid complex, NEEPN with its favorable in vivo kinetic characteristics clearly enhanced the gastrointestinal absorption and oral bioavailability of EDA; for example, the relative bioavailability of NEEPN to free EDA was calculated to be 630.35%, and the effective permeability of NEEPN in the colon was 8.64-fold that of EDA.Conclusion: NEEPN markedly improved the oral bioavailability of EDA, which was probably due to its increased gastrointestinal absorption. NEEPN also increased efficacy and reduced adverse effects for oral delivery of EDA. Such finding demonstrates great clinical significance as an ideal drug delivery system demands high efficacy and no adverse effects.Keywords: nanoemulsive system, evodiamine–phospholipid, nanocomplexes, gastrointestinal absorption, oral bioavailability, water-in-oil

Digui Weng, Menghua Huang, Runnian Jiang, Rufu Zhan, Chunni YangDepartment of Anesthesiology, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, People's Republic of ChinaBackground: The aim of this study was to investigate and evaluate the safety, recovery time, and side effects of general anesthesia with different doses of etomidate emulsion combined with remifentanil.Methods: One hundred ten patients of American Society of Anesthesiologists class 1 or 2 who underwent gynecological general anesthesia with a 1-3-hour operation time were randomly divided into the following groups: etomidate emulsion group 1 ([E1] n = 30); etomidate emulsion group 2 ([E2] n = 30); etomidate emulsion group 3 ([E3] n = 20); and propofol group ([P group] n = 30). For induction of anesthesia, 0.3 mg/kg etomidate emulsion, and the continuous remifentanil infusion also to induce anesthesia (0.1~0.3 µg · kg-1 · min-1), was applied in all cases. Afterwards, continuous infusion of etomidate emulsion and remifentanil, respectively (E1: 10 µg · kg-1 · min-1 and 0.1 µg · kg-1 · min-1; E2: 15 µg · kg-1 · min-1 and 0.2 µg · kg-1 · min-1; E3: 20 µg · kg-1 · min-1 and 0.2 µg · kg-1 · min-1), and propofol (P group: 6~10 mg · kg-1 · h-1) were administered. Changes in blood flow kinetics and adverse reactions were noted and compared between the four groups.Results: Both arterial blood pressure (BP) and heart rate (HR) decreased after induction of anesthesia (P < 0.05). Systolic (SBP) and diastolic (DBP) BP changed only slightly, and HRs were slightly infected in E1, E2, and E3. SBP, DBP, and HR during the operation all decreased significantly in P group (P < 0.05). Muscle tremor at the time of induction occurred in 13 cases (11.8%). Following etomidate emulsion anesthesia maintenance, postoperative agitation occurred in seven cases (8.75%), lethargy in 20 cases (25%), and vomiting in 19 cases (23.75%). No adverse reactions were found in P group.Conclusion: Continuous infusion of etomidate emulsion at 10 µg · kg-1 · minute-1 combined with remifentanil during anesthesia has the advantages of hemodynamic stability, quick wake-up, and few adverse reactions. Increasing the dose of etomidate emulsion increases the incidence of adverse reactions.Keywords: etomidate emulsion, remifentanil, general anesthesia

Qunyou Tan,1,* Rong Jiang,3,* Meiling Xu,2,4,* Guodong Liu,5,* Songlin Li,1 Jingqing Zhang21Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 2Medicine Engineering Research Center, Chongqing Medical University, 3Stem Cells and Tissue Engineering Research, Chongqing Medical University, 4Department of Pharmacy, Chongqing Emergency Medical Center, 5Eighth Department, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workBackground: Pyridostigmine bromide (3-[[(dimethylamino)-carbonyl]oxy]-1-methylpyridinium bromide), a reversible inhibitor of cholinesterase, is given orally in tablet form, and a treatment schedule of multiple daily doses is recommended for adult patients. Nanotechnology was used in this study to develop an alternative sustained-release delivery system for pyridostigmine, a synthetic drug with high solubility and poor oral bioavailability, hence a Class III drug according to the Biopharmaceutics Classification System. Novel nanosized pyridostigmine-poly(lactic acid) microcapsules (PPNMCs) were expected to have a longer duration of action than free pyridostigmine and previously reported sustained-release formulations of pyridostigmine.Methods: The PPNMCs were prepared using a double emulsion-solvent evaporation method to achieve sustained-release characteristics for pyridostigmine. The preparation process for the PPNMCs was optimized by single-factor experiments. The size distribution, zeta potential, and sustained-release behavior were evaluated in different types of release medium.Results: The optimal volume ratio of inner phase to external phase, poly(lactic acid) concentration, polyvinyl alcohol concentration, and amount of pyridostigmine were 1:10, 6%, 3% and 40 mg, respectively. The negatively charged PPNMCs had an average particle size of 937.9 nm. Compared with free pyridostigmine, PPNMCs showed an initial burst release and a subsequent very slow release in vitro. The release profiles for the PPNMCs in four different types of dissolution medium were fitted to the Ritger-Peppas and Weibull models. The similarity between pairs of dissolution profiles for the PPNMCs in different types of medium was statistically significant, and the difference between the release curves for PPNMCs and free pyridostigmine was also statistically significant.Conclusion: PPNMCs prepared by the optimized protocol described here were in the nanometer range and had good uniformity, with significantly slower pyridostigmine release than from free pyridostigmine. This novel sustained-release delivery nanosystem for pyridostigmine might alleviate the need to identify new acetylcholinesterase inhibitors.Keywords: nanosized microcapsules, process optimization, characteristics, sustained-release, pyridostigmine bromide