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Yang Deng,1,* Rui Duan,2,* Ye Hong,2,* Qiang Peng,2 Zhong-Yuan Li,2 Xiang-Liang Chen,2 Ying-Dong Zhang1 1Department of Neurology, Nanjing First Hospital, China Pharmaceutical University, Nanjing, 210006, People’s Republic of China; 2Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiang-Liang Chen, Department of Neurology, Nanjing First Hospital, Nanjing Medical University, No. 68, Changle Road, Nanjing, Jiangsu, 210006, People’s Republic of China, Email chenxl@njmu.edu.cn Ying-Dong Zhang, Department of Neurology, Nanjing First Hospital, China Pharmaceutical University, No.68, Changle Road, Nanjing, Jiangsu, 210006, People’s Republic of China, Email zhangyingdong@njmu.edu.cnPurpose: Vascular dementia (VaD) is the second most common dementia in the world. An increasing number of studies have demonstrated the important role of long non-coding RNAs (lncRNAs) in VaD. Our previous investigation demonstrated that Trimethylamine-N-oxide (TMAO) exacerbates cognitive impairment and neuropathological alterations in VaD rats. Thus, we hypothesized that TMAO could play an injury role in VaD by regulating lncRNAs.Materials and Methods: The rats using the bilateral common carotid artery (2VO) model were administered TMAO (120 mg/kg) for 8 consecutive weeks, 4 weeks preoperatively and 4 weeks postoperatively. High-throughput sequencing was conducted to investigate the effects of TMAO treatment on lncRNA expression in rat hippocampus and bioinformatics analysis was performed to identify potential downstream targets. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of lncRNA fetal-lethal noncoding developmental regulatory RNA (Fendrr), miR-145-5p, and paxillin (PXN). Learning and spatial memory capacities were measured, as well as inflammatory factors. Nissl staining was used to observe neuronal injury in the CA1 area of the hippocampus. Furthermore, we used the Fendrr loss-of-function assay, miR-145-5p gain-of-function assays and PXN loss-of-function assay to explore the mechanisms by which TMAO acts on VaD.Results: TMAO administration upregulated lncRNA Fendrr expression in the rat hippocampus, while the damaging effects of TMAO were counteracted after knockdown of Fendrr. Fendrr exhibits highly expressed in 2VO rats and sponged miR-145-5p, which targets PXN. Silencing of Fendrr or PXN, or promotion of miR-145-5p improved neurological function injury, reduced neuronal damage, as well as repressed inflammation response. Inhibition of miR-145-5p abrogated up Fendrr knockdown mediated influence on 2VO rats.Conclusion: The results of this study indicated that TMAO inhibits the miR-145-5p/PXN axis by increasing the Fendrr expression, thus exacerbating the development of VaD.Keywords: trimethylamine N-oxide, neuroinflammation, Fendrr, MiR-145-5p, PXN, vascular dementia

Xiao-Ling Shen,1,&ast; Zhuo-Yi Li,1,&ast; Qing Li,1 Kai Wang2 1Department of Women Health Care, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, People’s Republic of China; 2Department of Aristogenesis, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Wang; Qing Li, Email wangkai111909@163.com; lq5090@126.comPurpose: To verify whether there is lower incidence of adverse pregnancy outcomes after high-intensity focused ultrasound (HIFU) treatment than loop electrosurgical excision procedure (LEEP) in young women of childbearing age.Patients and Methods: This retrospective cohort study enrolled 46 patients treated with HIFU and 46 patients treated with LEEP. To compare the differences between the two groups, Fisher’s exact test or the Kruskal–Wallis (K-W/H) test was used in the univariate analysis, while the logistic regression method was applied for further verification.Results: Basic characteristics showed no differences between the two groups (P > 0.05) except for parity (P < 0.001). Preterm birth rates were 6.52% and 0.00% in patients with cervical high-grade squamous intraepithelial lesions (HSIL) treated with LEEP and HIFU, respectively. The incidence rates of premature rupture of membranes (PROM) were respectively 15.22% and 21.74% in the two groups. There was no significant difference in pregnancy outcomes between the two groups (P > 0.05).Conclusion: This study is the first to compare the pregnancy outcomes of patients with cervical HSIL who treated with LEEP and HIFU procedures. Both HIFU treatment and LEEP are available options for patients of reproductive age with cervical HSIL. Therefore, it is necessary to conduct prospective single-center or multicenter randomized controlled studies.Keywords: cervical high-grade squamous intraepithelial lesions, high-intensity focused ultrasound, loop electrosurgical excision procedure, pregnancy outcome

Cai-Dong Liu,1,2,&ast; Qiang Peng,3,&ast; Shi-Yao Wang,3,&ast; Yang Deng,2 Zhong-Yuan Li,3 Zhao-Han Xu,3 Liang Wu,3 Ying-Dong Zhang,2,3 Rui Duan3 1Department of Laboratory Medicine, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, 210006, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 210006, People’s Republic of China; 3Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying-Dong Zhang; Rui Duan, Department of Neurology, Nanjing First Hospital, Nanjing Medical University, No. 68, Changle Road, Nanjing, Jiangsu, People’s Republic of China, Email zhangyingdong@njmu.edu.cn; duanruicpu@163.comPurpose: Acute ischemic stroke (AIS) has seriously threatened people’s health worldwide and there is an urge need for early diagnosis and effective treatment of AIS. This research intended to clarify the regulatory role of circ_0008146/miR-342-5p/ACSL4 axis in AIS.Methods: High-throughput small RNA sequencing analysis was adapted to identify differentially expressed miRNAs between the AIS and control group. The circ_0008146, miR-342-5p, and ACSL4 levels were detected by qRT-PCR. Middle cerebral artery occlusion/reperfusion (MCAO/R) models were constructed in C57BL/6J mice. Assay kits were used to determine Fe2+ levels and a battery of oxidative stress and lipid peroxidation indicators, including ROS, MDA, LPO, SOD and GSH/GSSG ratio. The protein levels of ACSL4 were measured by Western blot. The behavioral function was assessed using neurobehavioral tests. TTC staining was employed to visualize infarction size. Nissl staining was adapted to detect histopathological changes. Receiver operating characteristic curve and correlation analysis were applied to investigate the clinical value and association of miR-342-5p and ACSL4.Results: A total of 44 AIS patients and 49 healthy controls were enrolled in our study. The small RNA sequencing unveiled a significant decrease in miR-342-5p levels in AIS patients. MiR-342-5p inhibited oxidative stress and RSL3-induced ferroptosis after cerebral ischemic/reperfusion injury in vivo by targeting ferroptosis-related gene ACSL4. Circ_0008146 acted as a sponge of miR-342-5p, and overexpression of circ_0008146 increased neurological deficits and brain injury in mice. Circ_0008146 contributed to ferroptosis in cerebral infarction via sponging miR-342-5p to regulate ACSL4. Plasma miR-342-5p and ACSL4 demonstrated significant correlation and good diagnostic value for AIS patients.Conclusion: This study provides the first in vivo evidence to show that circ_0008146 exacerbates neuronal ferroptosis after AIS via the miR-342-5p/ACSL4 axis. Furthermore, miR-342-5p/ACSL4 axis holds promise as a viable therapeutic target and practical biomarkers for AIS patients.Keywords: ischemic stroke, miRNA, circRNA, ferroptosis, biomarker

We carry out several numerical simulations to illustrate how the radial electric field (Er) impacts the edge magnetohydrodynamic (MHD) instabilities. The analyses reveal that Er-shear (Er′, here the prime denotes the derivative with respect to the radial direction) tends to stabilize the kink/Peeling–Ballooning modes by dephasing the perturbed radial velocity (ṽr) and displacement (ξ̃r). However, Er-curvature (Er″) tends to destabilize the kink/peeling modes by inducing a phase lock between ṽr and ξ̃r. More specifically, the ratio between them could be measured to quantify their relative competition strength. Consequently, the shape of Er is crucial to the shape of linear growth rate spectrum γ(n) (here n is the toroidal mode number), which further determines the nonlinear dynamics. On the one hand, relatively larger Er-curvature causes narrower γ(n), leading to larger nonlinear energy loss fraction. On the other hand, relatively larger Er-shear has the opposite effect.

Yan-Hua Chen,1 Xue-Luo Zhang,1 Zhong-Yun Li,2 Xian-Ping Wang,1 Jun Wang,3 Zhi-Ping Zhang,1 Peng-Fei Zhu,1 Xue-Qing Wu1 1Reproductive Medicine Center, Shanxi Maternal and Child Health Care Hospital, Taiyuan, People’s Republic of China; 2Rectum Branch, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan, People’s Republic of China; 3The Sixth Hospital of Shanxi Medical University (General Hospital of Tisco), Taiyuan, People’s Republic of ChinaCorrespondence: Xue-Qing Wu, Reproductive Medicine Center, Shanxi Maternal and Child Health Care Hospital, No. 13, Xinmin Middle Street, Xinghualing District, Taiyuan, Shanxi Province, 030013, People’s Republic of China, Tel +86 351-3360725, Email xueqingwu18@outlook.comObjective: This study aimed to evaluate the therapeutic efficacy and safety of Dan’e Fukang soft extracts in moderate ovarian hyperstimulation syndrome (OHSS) for the simultaneous treatment of blood and fluid, guided by the traditional Chinese medicine principle of “triple prevention”.Methods: This study conducted a retrospective analysis of clinical data from outpatients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection embryo transfer (ICSI-ET). A total of 2245 cases were included and divided into a treatment group (1002 cases) and a control group (1243 cases). Patients in the treatment group were administered Dan’e Fukang soft extracts orally in addition to conventional Western medicine. Comparative assessments were made between the two groups on pelvic ascites volume, maximum ovary diameter, dysmenorrhea incidence post-oocyte retrieval, and safety indicators.Results: There were no statistically significant differences between the treatment group and the control group in terms of general characteristics or the levels of follicle-stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), or progesterone (P) at the time of gonadotropin (Gn) initiation. The groups did not differ significantly when we compared the levels of LH, E2, or P on the day of human chorionic gonadotropin (hCG) injection and during ovarian hyperstimulation protocols (P > 0.05 for all indicators). The differences in the volume of pelvic ascites, the maximum ovarian diameter, and the incidence of dysmenorrhea after oocyte retrieval were statistically significant between the treatment group and the control group (P < 0.05 in both). There were no instances of adverse reactions in either group.Conclusion: Based on the traditional Chinese medicine principle of “triple prevention”, the use of Dan’e Fukang soft extracts for the simultaneous treatment of blood and fluid in moderate OHSS significantly improved the absorption of pelvic ascites, promoted ovarian recovery, and reduced the incidence of dysmenorrhea after oocyte retrieval.Keywords: Dan’e Fukang soft extracts, guiding principle of triple prevention, in vitro fertilization embryo transfer/intracytoplasmic sperm injection embryo transfer, ovarian hyperstimulation syndrome, simultaneous treatment of blood and fluid

Jin Chen,1,2,&ast; Zhi-Yong Li,2,&ast; Fei Xu,2,&ast; Chao-Qun Wang,1 Wen-Wen Li,1 Jin Lu,1 Chao-Yu Miao2 1Department of Endocrinology and Metabolism, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, People’s Republic of China; 2Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao-Yu Miao, Department of Pharmacology, Second Military Medical University/Naval Medical University, 325 Guo He Road, Shanghai, 200433, People’s Republic of China, Email cymiao@smmu.edu.cn Jin Lu, Department of Endocrinology and Metabolism, Changhai Hospital, Second Military Medical University/Naval Medical University, 168 Chang Hai Road, Shanghai, 200433, People’s Republic of China, Email lujin-sh@139.comObjective: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Metrnl is a secreted protein that plays an important role in kidney disease. The aim of this study was to investigate DKD-related factors and the correlation between serum Metrnl levels and the severity of DKD.Methods: Ninety-six type 2 diabetes mellitus (T2DM) patients and 45 DKD patients were included in the study. A range of parameters were measured simultaneously, including waist-to-hip ratio (WHR), body mass index (BMI), urinary albumin/creatinine ratio (UACR), monocyte–lymphocyte ratio (MLR), albumin/globulin (A/G), liver and kidney function, blood lipid profile, islet function, and others. Subsequently, the related factors and predictive significance of DKD were identified. The correlation between the relevant factors of DKD and serum Metrnl levels with DKD was evaluated.Results: The duration of the disease (OR: 1.12, 95% CI: 1.01– 1.24, P=0.031), hypertension (OR: 4.86, 95% CI: 1.16– 20.49, P=0.031), fasting blood glucose (OR: 1.23, 95% CI: 1.03– 1.48, P=0.025), WHR (OR: 2.53, 95% CI: 1.03– 6.22, P=0.044), and MLR (OR: 1.91, 95% CI: 1.18– 3.08, P=0.008) are independent risk factors for DKD (P < 0.05). Conversely, A/G (OR: 0.13, 95% CI: 0.02– 0.76, P=0.024) and Metrnl (OR: 0.99, 95% CI: 0.98– 1.00, P=0.001) have been identified as protective factors against DKD. Furthermore, the level of Metrnl was negatively correlated with the severity of DKD (rs=− 0.447, P< 0.001). The area under receiver operating characteristic (ROC) curves for the diagnostic accuracy of Metrnl for DKD is 0.765 (95% CI: 0.686– 0.844).Conclusion: The duration of the disease, hypertension, fasting blood glucose, WHR, and MLR are major risk factors for DKD. Metrnl and A/G are protective factors for DKD. Serum Metrnl concentrations are inversely correlated with DKD severity.Keywords: diabetic kidney disease, urinary albumin/creatinine ratio, Metrnl, albumin/globulin

Juan Pan,1 Chao Ye,2 Ling-Zhi Zhou,1 Zu-Yi Li,1 Juan Wang,2 Xin He,2 Shen-Jue Chen,2 Guang-Qing Zhou2 1Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Chao Ye, Department of Pharmacy, The Third Hospital of Changsha, No. 176 Laodong West Road, Tianxin District, Changsha, Hunan, 410015, People’s Republic of China, Email yechao1234256@163.com Ling-Zhi Zhou, Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, No. 67, Beizheng Middle Road, Changsha, Hunan, 410300, People’s Republic of China, Email 1024482174@qq.comIntroduction: Tigecycline-induced acute pancreatitis (AP) has been frequently increasingly reported in solid organ transplant patients. This review aimed to summarize the characteristics, possible mechanisms, and management of tigecycline-induced AP.Methods: Case reports of tigecycline-induced AP published in Chinese or English were collected until February 2023 for retrospective analysis.Results: Thirty-four patients from 29 articles were included. Fifteen patients (46.9%) had solid organ transplantation, and 4 patients (12.5%) had malignant tumors. Twenty-five patients (89.3%) received a recommended maintenance dose of tigecycline (50 mg q12 h). The median age was 50 years (range 9– 87). Compared to the nontransplant patients, the median age of the transplant patients was significantly younger, 44 years (range 12.5– 61) versus 57.5 years (range 9– 87) (P=0.03). The median time of symptom onset was 7 days (range 2– 29), and 91.2% (31/34) were less than 14 days. Typical initial symptoms included abdominal pain (90.6%), nausea (46.9%), vomiting (43.8%), and abdominal distention (21.9%). Most cases were accompanied by elevated levels of pancreatic enzymes. The main radiological features included edematous infiltrate and acute pancreatitis on computed tomography (CT) scan and abdominal ultrasound. Except for one patient who continued tigecycline treatment, all patients discontinued treatment and received symptomatic support such as fasting, acid suppression, and enzyme suppression. The median time to recover pancreatic enzymes to the normal range was 5 days (range 1– 43), and the median time to relieve symptoms was 4 days (range 1– 12). Four patients died, of whom two died of severe pancreatitis complications and two of cardiogenic shock and septicemia.Conclusion: Tigecycline-induced AP was a rare and serious complication that occurred mainly within two weeks of the medication. This serious side effect should be kept in mind while treating severe infections especially in transplant recipients.Keywords: tigecycline, pancreatitis, adverse drug reaction, solid organ transplantation

Mei-Ling Xia,1 Wen-Xuan Lin,2 Ling-Ling Gao,3 Mao-Ling Zhang,1 Zhi-Yun Li,4 Li-Ling Zeng4 1Reproductive Centre, Guangdong Women and Children Hospital, Guangzhou, People’s Republic of China; 2Nursing Department, Guangdong Women and Children Hospital, Guangzhou, People’s Republic of China; 3School of Nursing, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Obstetric Department, Guangdong Women and Children Hospital, Guangzhou, People’s Republic of ChinaCorrespondence: Ling-Ling Gao, School of Nursing, Sun Yat-sen University, Guangzhou, People’s Republic of China, Tel +86-20-87335013, Fax +86-20-87333043, Email gaoll@mail.sysu.edu.cnPurpose: Knowledge of the readiness for hospital discharge can help health care professionals accurately determine the patients’ discharge time. However, few studies were on the readiness for discharge and its related factors among mothers with cesarean sections. Thus, this study aims to examine the readiness for hospital discharge and its associated factors among Chinese mothers with cesarean sections.Patients and Methods: A single-centre cross-sectional study was conducted from September 2020 to March 2021 in Guangzhou, China. Three hundred thirty-nine mothers with cesarean sections completed the questionnaires on demographic and obstetric characteristics, readiness for hospital discharge, quality for discharge teaching, parenting sense of competence, family function, and social support. Multiple linear regression analysis was used to identify independent factors influencing readiness for hospital discharge among mothers with cesarean sections.Results: The total score of readiness for hospital discharge was 136.47 ± 25.29. The quality of discharge teaching, parenting sense of competence, number of cesareans, family function, and attending antenatal classes were independent factors influencing the readiness for hospital discharge (P

Wang Tang1 &ast;, Zhen-Wei Li1 &ast;, Gui-Qiang Miao2 &ast;, Zhi-Peng Li,1 Tao Gui,1 Chong-Jie Wu,1 Zhen-Yan Li,1 Jie Yang,1 Xiao-Dong Zhao,2 Ning Liu,1 Zhen-Gang Zha,1 Lu-Tian Yao,3 Huan-Tian Zhang1 1Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 2Department of Orthopedics, Foshan Fosun Chancheng Hospital, Foshan, 528010, People’s Republic of China; 3Department of Orthopedics, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu-Tian Yao; Huan-Tian Zhang, Email ltyao@cmu.edu.cn; zhanghuantian@jnu.edu.cnPurpose: Subchondral insufficiency fracture of the knee (SIFK) is a common cause of knee joint pain that mainly afflicts the elderly. Until now, how a sudden insufficiency fracture of subchondral bone affects the transcriptomic profiles of cartilage in SIFK and OA patients are largely unknown.Methods: Single-cell RNA sequencing (scRNA-seq) was used to identify various cell subsets and evaluate transcriptomic differences in cartilage of SIFK and OA patients. In addition, the above findings were confirmed by histological evaluation and immunohistochemical (IHC) staining.Results: We found that the transcriptomic profiles of cartilage in the SIFK patient was completely different from those of normal and OA patients. Accordingly, several novel cell clusters with activation of hypoxia and endochondral ossification signaling were identified in the SIFK cartilage. Chondrocyte trajectories analysis and IHC staining revealed that transcription factors including TCF4 were found to be highly up-regulated during the occurrence of SIFK, which might drive the reactive formation of cartilage and fibrous tissue and the activation of endochondral ossification.Conclusion: This is the first report to elucidate the transcriptomic alterations and distinct cell type subpopulations in the cartilage of SIFK and OA by the use of scRNA-seq, which provides a new insight in the understanding of the initiation and progression of SIFK.Keywords: SIFK, scRNA, TCF4, cartilage, hypoxia

Mei-Qi Xu,1,2 Yan-Li Hao,1,2 Jing-Ru Wang,1,2 Zhuo-Yue Li,1,2 Hui Li,1 Zhen-Han Feng,1,2 Hui Wang,1,2 Jing-Wen Wang,1,2 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People’s Republic of ChinaCorrespondence: Xuan ZhangDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing, 100191, People’s Republic of ChinaTel +86-10-82805765Fax +86-10-8280576Email xuanzhang@bjmu.edu.cnPurpose: Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acid-paclitaxel conjugate nanoparticles (ALA-PTX NPs), in order to obtain better tumor cellular uptake and antitumor activity in vitro and in vivo.Methods: We synthesized and characterized ALA-PTX, and then prepared and characterized ALA-PTX NPs. The cellular uptake, uptake pathways, intracellular behavior, in vitro and in vivo antitumor activity of ALA-PTX NPs were evaluated.Results: The size of ALA-PTX NPs was approximately 110.7± 1.7 nm. The drug loading was approximately 90% (w/w) with CrEL-free and organic solvent-free characteristics. The cellular uptake of ALA-PTX NPs was significantly higher than that of PTX injection by MCF-7, MCF-7/ADR and HepG2 cells. In these three cell lines, the cellular uptake of ALA-PTX NPs at 6h was approximately 1.5– 2.6 times higher than that of PTX injection. ALA-PTX NPs were ingested through clathrin-mediated endocytosis, then transferred to lysosomes, and could dissolve in cells to play an antitumor activity. The in vitro and in vivo antitumor activity of ALA-PTX NPs was confirmed in MCF-7/ADR and HepG2 cell models and tumor-bearing nude mouse models.Conclusion: ALA-PTX NPs developed in our study could provide a new method for the preparation of nano-delivery systems suitable for antitumor therapy that could increase tumor cellular uptake and enhance antitumor activity.Keywords: α-linolenic acid, α-linolenic acid-paclitaxel conjugate, α-linolenic acid-paclitaxel conjugate nanoparticles, cellular uptake, antitumor activity

Shao-Jie Zhang,1,2,&ast; Kun Li,2,3,&ast; Zhi-Jun Li,2,3 Xing Wang,2,3 Jia-Hui Dong,4 Jian Wang,2 Jie Chen,2 Xing-Yue Qu,2 Zi-Yu Li,2 Yu-Hang Liu2 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Human Anatomy, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 3Digital Medical Center, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 4The First Clinical Medical College, Inner Mongolia Medical University, Hohhot, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Jun LiDepartment of Human Anatomy, Inner Mongolia Medical University, Hohhot, People’s Republic of ChinaTel +86 471-6636945Email zjl06_master@126.comObjective: This study aimed to investigate the safety of clival screw placement in children aged 1– 6 years.Methods: The cranial computed tomography data of 92 children aged 1– 6 years were divided into three groups, according to age, for three-dimensional reconstruction. Three clival screw placement points were defined: (1) median point A at the middle and upper third of the tripartite distance from the spheno-occipital synchondrosis to the base of the skull; (2, 3) critical points B and C on the horizontal line with point A, where the screw placement passage was parallel to the sagittal plane. Parameters such as the passage length and angle were measured for horizontal, vertical facial, and extreme screw placement.Results: The length parameters of the clival screw placement increased with age, and the screw passage length was the shortest for the vertical facial type in each age group. There were significant differences in all three groups between the length of screw placement in the vertical bone surface, the length of screw placement in the horizontal direction, and the length of screw placement on the limit at points A, B, and C (P < 0.05); the length of screw placement on the vertical bone surface was the shortest. There was no significant difference between the horizontal screw length at point A and the extreme screw length (P > 0.05). The difference between the horizontal screw length and the extreme screw length in the groups aged 1– 2 years and 5– 6 years was statistically significant (P < 0.05), and the horizontal screw length was longer.Conclusion: The cranial slope of children aged 1– 6 years has the morphological basis for the placement of 3.5 mm screws, and each placement point has a safe angle range for screw placement.Keywords: children, craniocervical junction region, clivus, internal screw fixation, spiral computed tomography scan

Many recent observations and numerical simulations suggest that nearby massive, early-type galaxies (ETGs) were formed through a "two-phase" process. In the proposed second phase, the extended stellar envelope was accumulated through many dry mergers. However, details of the past merger history of present-day ellipticals, such as the typical merger mass ratio, are difficult to constrain observationally. Within the context and assumptions of the two-phase formation scenario, we propose a straightforward method, using photometric data alone, to estimate the average mass ratio of mergers that contributed to the build-up of massive elliptical galaxies. We study a sample of nearby massive elliptical galaxies selected from the Carnegie-Irvine Galaxy Survey, using two-dimensional analysis to decompose their light distribution into an inner, denser component plus an extended, outer envelope, each having a different optical color. The combination of these two substructures accurately recovers the negative color gradient exhibited by the galaxy as whole. The color difference between the two components (〈Δ(B-V)〉 ≃ 0.10 mag; 〈Δ(B-R) 〉 ≃ 0.14 mag), based on the slope of the M∗-color relation for nearby ETGs, can be translated into an estimate of the average mass ratio of the mergers. The rough estimate, 1:5 to 1:10, is consistent with the expectation of the two-phase formation scenario, suggesting that minor mergers were largely responsible for building up the outer stellar envelopes of present-day massive ellipticals. With the help of accurate photometry, large sample sizes and more choices of colors promised by ongoing and future surveys, the approach proposed here can provide more insights into the growth of massive galaxies during the last few Gyr.

Wang Zheng,1 Zong-Yu Li,1 De-Lai Zhao,1,2 Xing-Long Li,1,2 Rui Liu3 1Department of Burns, The Fifth Hospital of Harbin, Harbin 150040, People’s Republic of China; 2Department of Orthopedic Surgery, The Fifth Hospital of Harbin, Harbin 150040, People’s Republic of China; 3Department of Burns, Heilongjiang Provincial Hospital, Harbin 150036, People’s Republic of ChinaCorrespondence: Rui LiuDepartment of Burns, Heilongjiang Provincial Hospital, No. 82, Zhongshan Road, Xiangfang District, Harbin 150036, People’s Republic of ChinaTel +86-13268968547Email liurui435342@163.comPurpose: To investigate the specific effect and underlying mechanism of microRNA-26a-5p (miR-26a) in cutaneous squamous cell carcinoma (CSCC).Methods: miR-26a and MMP14/16 mRNA expression were detected by qRT-PCR analysis. Functional experiments were used to detect the role of miR-26a on CSCC progression. Western blot was used for protein detection. Luciferase assay was used to detect miR-26a directly targeting MMP14 and MMP16. Xenograft nude mice model was used to determine the effect of miR-26a on tumorigenesis.Results: miR-26a was decreased in CSCC tissues and cells. Forced miR-26a suppressed the progression of SCL-1 and A431 cells. Furthermore, miR-26a directly targeted MMP14 and MMP16 to inhibit their expression. Forced expression of MMP14 and MMP16 removed the miR-26a’s inhibitory effect on CSCC development. The in vivo tumor growth assay showed that miR-26a suppressed CSCC tumorigenesis by targeting MMP14 and MMP16.Conclusion: Our study suggested miR-26a inhibits cancer cell proliferation, migration and invasion in CSCC by targeting MMP14 and MMP16. Keywords: miR-26a, cutaneous squamous cell carcinoma, MMP14, MMP16, tumorigenesis

Zhuo-Yue Li,1,2 Yi-Fan Yin,1,2 Yang Guo,1,2 Hui Li,1,2 Mei-Qi Xu,1,2 Man Liu,1,2 Jing-Ru Wang,1,2 Zhen-Han Feng,1,2 Xiao-Chuan Duan,1,2 Shuang Zhang,1,2 Shuai-Qiang Zhang,1,2 Guang-Xue Wang,2 Ai Liao,2 Shu-Min Wang,3 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China; 3Department of Ultrasound, Peking University Third Hospital, Peking University, Beijing 100191, People’s Republic of ChinaCorrespondence: Xuan ZhangDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing 100191, People’s Republic of ChinaTel/Fax +86-10-82805765Email xuanzhang@bjmu.edu.cnShu-Min WangDepartment of Ultrasound, Peking University Third Hospital, Peking University, Xueyuan Road 38, Beijing 100191, People’s Republic of ChinaEmail shuminwang2014@163.comIntroduction: Because tumor-associated inflammation is a hallmark of cancer treatment, in the present study, sorafenib mesoporous silica nanomatrix (MSNM@SFN) co-administrated with flufenamic acid (FFA, a non-steroidal anti–inflammatory drug (NSAID)) was investigated to enhance the anti-tumor activity of MSNM@SFN.Methods: Metastatic breast tumor 4T1/luc cells and hepatocellular carcinoma HepG2 cells were selected as cell models. The effects of FFA in vitro on cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in 4T1/luc and HepG2 cells were investigated. The in vivo anti-tumor activity of MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) was evaluated in a 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model, respectively.Results: The results indicated that FFA could markedly decrease cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in both 4T1/luc and HepG2 cells. The enhanced anti-tumor activity of MSNM@SFN+FFA compared with that of MSNM@SFN was confirmed in the 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model in vivo, respectively.Discussion: MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) developed in this study is an alternative strategy for improving the therapeutic efficacy of MSNM@SFN via co-administration with NSAIDs.Keywords: sorafenib mesoporous silica nanomatrix, MSNM@SFN, flufenamic acid, FFA, PGE2, AKR1C1, AKR1C3, 4T1/luc, HepG2

Bo Sun,1,* Yan-Tian Fang,1,* Dan-Juan Jin,2 Zong-You Chen,3 Zhen-Yang Li,3 Xiao-Dong Gu,3 Jian-Bin Xiang3 1Department of Gastric Cancer, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of General Surgery, Songjiang District Central Hospital, Shanghai, People’s Republic of China; 3Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Dong Gu; Jian-Bin XiangDepartment of General Surgery, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, People’s Republic of ChinaTel +86-21-5288 7044; +86-21-5288 7040Fax +86-21-62495490Email gxdgxd737@163.com; xjbzhw131@sohu.comPurpose: Colorectal cancer (CRC) stem cells are tumorigenic, capable of self-renewal, and resistant to therapy. Although the expression pattern and functions of micro RNA (miR)-194 in CRC cells have been widely investigated, little is known about its role in CRC stem cells. Therefore, the aim of this study was to investigate the potential role of miR-194 in CRC stem cells.Materials and methods: CRC stem cells were isolated from the SW620 colon cancer cell line using microbeads. The expression levels of miR-194 and slingshot 2 (SSH2) in CRC stem cells were detected by RT-PCR and Western blot. A luciferase reporter assay was performed to confirm that miR-194 directly targets SSH2. Proliferation of CRC stem cells was examined by colony formation and MTT assays. Apoptosis in CRC stem cells was detected by cell cycle and apoptosis assays. The role of miR-194 in tumor growth was determined in vivo.Results: Cells positive for CD44 and CD133 accounted for approximately 88.7% of the isolated population after microbead isolation. We reveal for the first time that miR-194 expression is decreased in CRC stem cells. Specifically, miR-194 is involved in inhibiting the proliferation of CRC stem cells and promoting CRC stem cell apoptosis by directly targeting SSH2. Furthermore, overexpression of miR-194 resulted in blocking the G1/S transition, the induction of cellular apoptotic process, thereby suppressing the malignant behaviors of CRC stem cells.Conclusion: This study represents a novel characterization of miR-194 function in CRC stem cells, which may aid in the development of promising therapeutic strategies targeting CRC.Keywords: colorectal cancer, miR-194, SSH2, proliferation, stem cell

Xiao-Ya Qin,1,2,* Xiao-Xin Liu,1,2,* Zi-Yuan Li,1,2 Li-Ying Guo,1,2 Zhuo-Zhao Zheng,3 Hai-Tao Guan,4 Li Song,4 Ying-Hua Zou,4 Tian-Yuan Fan1,2 1The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 3Department of Nuclear Medicine, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 4Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tian-Yuan FanDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road No.38, Haidian District, Beijing 100191, People’s Republic of ChinaTel/fax +86 10 8280 5123Email tianyuan_fan@bjmu.edu.cnObjective: The objective of this study was to develop magnetic embolic microspheres that could be visualized by clinical magnetic resonance imaging (MRI) scanners aiming to improve the efficiency and safety of embolotherapy.Methods and discussion: Magnetic ferrite nanoclusters (FNs) were synthesized with microwave-assisted solvothermal method, and their morphology, particle size, crystalline structure, magnetic properties as well as T2 relaxivity were characterized to confirm the feasibility of FNs as an MRI probe. Magnetic polymer microspheres (FNMs) were then produced by inverse suspension polymerization with FNs embedded inside. The physicochemical and mechanical properties (including morphology, particle size, infrared spectra, elasticity, etc.) of FNMs were investigated, and the magnetic properties and MRI detectable properties of FNMs were also assayed by vibrating sample magnetometer and MRI scanners. Favorable biocompatibility and long-term MRI detectability of FNMs were then studied in mice by subcutaneous injection. FNMs were further used to embolize rabbits’ kidneys to evaluate the embolic property and detectability by MRI.Conclusion: FNMs could serve as a promising MRI-visualized embolic material for embolotherapy in the future.Keywords: polymerized microspheres, magnetic ferrite nanoclusters, magnetic resonance imaging, embolization, microwave-assisted solvothermal method

Yan Huang,1,2,* Dan Zhang,1,3,* Zhi-Yuan Li,4,* Yan-Ting Yang,3 Li-Jie Wu,1 Ji Zhang,1 Fang-Yuan Zhi,1 Xi-Ying Li,1 Zheng Shi,3 Jue Hong,3 Xiao-Peng Ma1,3 1Yueyang Clinical Medical School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China; 2Acupuncture and Moxibustion Department, Huangpu District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200010, People’s Republic of China; 3Laboratory of Acupuncture, Moxibustion, and Immunology, Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, People’s Republic of China; 4Acupuncture and Moxibustion Department, Zhejiang Provincial Hospital of TCM, Hangzhou, Zhejiang 310006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Peng MaShanghai Research Institute of Acupuncture and Meridian, No. 650 South Wanping Road, Xuhui District, Shanghai, People’s Republic of ChinaTel +86 021 64690257Fax +86 021 64382181Email pengpengma@163.comPurpose: The purpose of this study was to explore the central analgesia mechanism of moxibustion for chronic inflammatory visceral pain (CIVP).Methods: A CIVP rat model was established by 2,4,6-trinitrobenzene sulfonic acid (TNBS) plus 50% ethanol via enema. The analgesic effect of moxibustion was evaluated using the abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL). The expression profile of phosphorylated proteins of the mitogen-activated protein kinase (MAPK) signaling pathway in the spinal cord was assayed by protein microarray. The differentially expressed proteins were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional clusters and corresponding signaling pathways.Results: Moxibustion exerted a significant analgesic effect for CIVP rats, mainly presenting as a decrease in the AWR score (all P1.3 or

Ting Wen Yi Hu1,2, Xiu Ming1, Hao Zheng Yan1, Zheng Yu Li1,2 1Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Zheng Yu LiWest China Second University Hospital, Sichuan University, No. 20 Section 3, Renmin South Road, Chengdu, Sichuan 610041, People’s Republic of ChinaTel +86 1 898 215 1025Fax +86 28 8 550 2391Email zhengyuli@scu.edu.cnPurpose: The study aimed to explore the survival outcomes of early-stage cervical cancer (CC) patients treated with laparoscopic/abdominal radical hysterectomy (LRH/ARH).Patients and Methods: We performed a retrospective analysis involving women who had undergone LRH/ARH for CC in early stage during the 2013–2015 period in West China Second University Hospital. The survival outcomes and potential prognostic factors were evaluated using Kaplan–Meier method and Cox regression analysis, respectively.Results: A total of 678 patients were included in our analysis. The overall survival (OS) and progression-free survival (PFS) between the ARH (n=423) and LRH (n=255) groups achieved no significant differences (p=0.122, 0.285, respectively). However, in patients with a tumor diameter >4 cm, the OS of the LRH group was significantly shorter than that of the ARH group (p=0.017). Conversely, in patients with a tumor diameter ≤4 cm, the LRH group had a significantly longer OS than the ARH group (p=0.013). The multivariate Cox analysis revealed that International Federation of Gynecology and Obstetrics stage, histology, parametrial invasion, and pelvic lymph node invasion were independent prognostic factors for OS and PFS, whereas surgical method was not a statistically significant predictor of OS (p=0.806) or PFS (p=0.236) in CC patients.Conclusion: LRH was an alternative to ARH for surgical treatment of CC patients with a tumor diameter ≤4 cm. However, for the patients with a tumor diameter >4 cm, priority should be given to ARH.Keywords: cervical cancer, laparoscopy, hysterectomy, prognosis

Yong-Liang Yuan,1,* Neng Jiang,2,* Ze-Yun Li,1 Zhi-Zhen Song,1 Zhi-Heng Yang,1 Wen-Hua Xue,1 Xiao-Jian Zhang,1 Yue Du11Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Pharmacy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of ChinaCorrespondence: Yong-Liang Yuan; Yue DuDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road 1, Zhengzhou, Henan 450052, People’s Republic of ChinaTel/fax +86 03 716 629 5651Email yylcpu@126.com; fccduy@zzu.edu.cn*These authors contributed equally to this workPurpose: Polyphyllin VI, a main active saponin isolated from traditional medicinal plant Paris polyphylla, has exhibited antitumor activities in several cancer cell lines. In the present study, we investigated the antitumor effect of Polyphyllin VI against human osteosarcoma cells (U2OS) and the underlying molecular mechanisms.Methods: The U2OS cell lines were used to determine the antiproliferative effect of Polyphyllin VI by CCK8 assay. Cell cycle was analyzed by flow cytometry. The Polyphyllin VI-induced apoptosis was determined by Annexin V-APC/7-AAD apoptosis detection kit and JC-1 staining. Meanwhile, the autophagy was determined by acridine orange staining. The apoptosis and autophagy-related proteins were monitored by Western blot assay. Subsequently, intracellular hydrogen peroxide (H2O2) and the activation of ROS/JNK pathway were detected.Results: Polyphyllin VI could potently inhibit cell proliferation by causing G2/M phase arrest. Polyphyllin VI induced mitochondria-mediated apoptosis with the upregulation of proapoptotic proteins Bax and poly ADP-ribose polymerase, and downregulation of antiapoptotic protein Bcl-2 in U2OS cells. Concomitantly, Polyphyllin VI provoked autophagy with the upregulation of critical Atg proteins and accumulation of LC3B-II. Intracellular H2O2 production was triggered upon exposure to Polyphyllin VI, which could be blocked by ROS scavenger. Polyphyllin VI dramatically promoted JNK phosphorylation, whereas it decreased the levels of phospho-p38 and ERK.Conclusion: Our results reveal that Polyphyllin VI may effectively induce apoptosis and autophagy to suppress cell growth via ROS/JNK activation in U2OS cells, suggesting that Polyphyllin VI is a potential drug candidate for the treatment of osteosarcomas.Keywords: Polyphyllin VI, osteosarcoma, apoptosis, autophagy, JNK activation

Accelerator mass spectrometry (AMS) measurement of 59Ni has been established at CIAE with the HI-13 tandem accelerator and the recently developed ΔE-Q3D detection system. 59Ni standard and commercial NiO samples were measured to check the performance of the ΔE-Q3D detection system on 59Ni isobar separation and suppression. An overall suppression factor of about 107 for the interfering isobar 59Co resulting in detection sensitivity as low as 3.8 × 10 -13 atomic ratio (59Ni/Ni) has been obtained. Based on these techniques, the AMS measurement method of 59Ni with high sensitivity is developed. © 2013 Chinese Physical Society and the Institute of High Energy Physics of the Chinese Academy of Sciences and the Institute of Modern Physics of the Chinese Academy of Sciences and IOP Publishing Ltd. © 2013 Chinese Physical Society.

Zheng W, Li ZY, Zhao DL, Li XL, Liu R. Cancer Manage Res. 2020;12:7087-7095. The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised over the alleged image duplication if Figure 6B with similar images from unrelated articles, specifically: Figure 6B, all panels, appear to have been duplicated with similar images in Figure 5B from Mu et al (https://doi.org/10.18632/aging.103918) and Figure 6B from Zhao et al, 2020 (https://doi.org/10.18632/aging.103275). The authors did not respond to our queries and the Editor determined the findings of the study were no longer valid and advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Yichen Huang,1,* Xing Shi,2,* Zhiyong Li,1,* Yang Shen,1,* Xinxin Shi,1 Liying Wang,3 Gaofei Li,3 Ye Yuan,2 Jixiang Wang,4 Yongchao Zhang,4 Lei Zhao,4 Meng Zhang,4 Yu Kang,2 Ying Liang1 1National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China; 2CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; 3Department of Psychiatry, Beijing Hospital of Chinese Traditional and Western Medicine, Beijing, China; 4Beijing Gene Tangram Technology Co. Ltd, Beijing, China *These authors contributed equally to this work Background: Gut microbiota can affect human behavior and mood in many ways. Several studies have shown that patients with depression were also accompanied with gut microbiota disorder, in which Firmicutes are related to the protective function of intestinal barrier. In this study, we explore the changes and effects of Firmicutes in the patients with major depressive disorder (MDD). Method: We recruited 54 subjects, including 27 patients with MDD. Fecal samples were collected for identification by 16S rRNA sequencing and bioinformatics analysis. Results: The study shows that the alpha diversity indices of MDD patients are lower than those of the healthy controls. Firmicutes is the most significantly decreased phylum in the MDD samples. There are totally 13 taxonomic biomarkers with P-value

Min-Wei Zhou,1,* Xiao-Yun Huang,2,* Zong-You Chen,1 Zhen-Yang Li,1 Yi-Ming Zhou,1 Yi Yang,1 Zi-Hao Wang,1 Jian-Bin Xiang,1 Xiao-Dong Gu1 1Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Electromyogram, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Some patients with low rectal cancer experience anorectal and urogenital dysfunctions after surgery, which can influence the long-term quality of life. In this study, we aimed to protect nerve function in such scenarios by performing intraoperative monitoring of pelvic autonomic nerves (IMPAN). Patients and methods: We retrospectively investigated a series of 87 patients undergoing laparoscopic low anterior resection of rectal cancer. Nerve-sparing was evaluated both visually and electrophysiologically. IMPAN was performed by stimulating the pelvic autonomic nerves under processed electromyography of the internal anal sphincter. Urination, defecation, sexual function, and the quality of life were evaluated using validated and standardized questionnaires preoperatively and at follow-up, 12 months after surgery. Results: Among a total of 87 patients (53 male and 34 female patients), IMPAN with simultaneous electromyography of the internal anal sphincter was performed in 58 (66.7%) patients. Bilateral positive IMPAN results for both measurements, indicating successfully confirmed pelvic autonomic nerve preservation, were obtained in 45 (51.7%) patients. No significant difference was found in terms of urogenital and anorectal functions between preoperative and postoperative patients with bilateral positive IMPAN (P>0.05). Compared to preoperative patients with IMPAN (unilateral) or without IMPAN, these patients exhibited higher International Prostate Symptom Score, a lower International Index of Erectile Function-5, and a lower Female Sexual Function Index score at 12 months postoperatively (P

Ting Wen Yi Hu,1 Dan Nie,1,2 Jin Hai Gou,1,3 Zheng Yu Li1,3 1Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China; 3The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Background: Computed tomography (CT) has been extensively used in predicting suboptimal cytoreduction (SCR) in advanced ovarian cancer (OC). However, disagreements remain in literatures on the predictive value of CT findings for SCR. This meta-analysis was designed to determine the ability of eight preoperative CT findings to predict SCR in advanced OC. Materials and methods: A comprehensive literature search was conducted for eligible studies to identify the association between the eight preoperative CT findings and SCR in advanced OC. The predictive performances of preoperative CT findings were expressed in terms of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) with pooled proportion. Results: A total of 10 studies and 1,614 patients were included in this meta-analysis. Large volume ascites had the highest sensitivity (64%, CI 56–71%), with a PLR of 1.3 (CI 1.1–1.5) and an NLR of 0.73 (0.59–0.90), while lymph node involvement had the highest specificity (89%, CI 79–94%). The highest DOR of 3 (CI 2–4) was achieved in peritoneal involvement and large bowel mesentery involvement. The other CT findings had poorer predictive performance. Conclusion: Preoperative CT findings have a poor discriminative capacity to predict SCR in advanced OC. Preoperative CT predictors should be used with caution amid clinical decision-making. Keywords: computed tomography, suboptimal cytoreduction, ovarian cancer, meta-analysis, predict

Xiao-long Wu,1,* Zhi-yu Li,1,* Xin-yu Bi,1 Hong Zhao,1 Jian-jun Zhao,1 Jian-guo Zhou,1 Yue Han,2 Zhen Huang,1 Ye-fan Zhang,1 Jian-qiang Cai1 1Department of Hepatobiliary Surgery, 2Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China *These authors contributed equally to this work Background: Systemic inflammation (SI) is associated with tumor progression and overall survival (OS) in patients with hepatocellular carcinoma (HCC). The presence of some single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can influence the prognosis of patients with hepatitis B virus (HBV)-related HCC, although the mechanism remains unknown. This study aimed to analyze the correlations between HLA gene polymorphisms and SI. Patients and methods: This study included 330 patients with HCC. The clinical parameters were reviewed, and five SNPs, namely rs2647073, rs3997872, rs3077, rs7453920, and rs7768538, were genotyped using the MassARRAY system. Results: The rs3997872, rs7453920, and rs7768538 genotypes were found to be significantly associated with OS (P

Xiu-Chai Zheng,1,2,* Wei Ren,1,2,* Shuang Zhang,1,2 Ting Zhong,1,2 Xiao-Chuan Duan,1,2 Yi-Fan Yin,1,2 Mei-Qi Xu,1,2 Yan-Li Hao,1,2 Zhan-Tao Li,1,2 Hui Li,1,2 Man Liu,1,2 Zhuo-Yue Li,1,2 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China *These authors contributed equally to this work Background: In the present study, the tumor-specific, pH-responsive peptide H7K(R2)2 -modified, theranostic liposome-containing paclitaxel (PTX) and superparamagnetic iron oxide nanoparticles (SPIO NPs), PTX/SPIO-SSL-H7K(R2)2, was prepared by using H7K(R2)2 as the targeting ligand, SPIO NPs as the magnetic resonance imaging (MRI) agent, PTX as antitumor drug. Methods: The PTX/SPIO-SSL-H7K(R2)2 was prepared by a thin film hydration method. The characteristics of PTX/SPIO-SSL-H7K(R2)2 were evaluated. The targeting effect, MRI, and antitumor activity of PTX/SPIO-SSL-H7K(R2)2 were investigated detail in vitro and in vivo in human breast carcinoma MDA-MB-231 cell models. Results: Our results of in vitro flow cytometry, in vivo imaging, and in vivo MR imaging confirmed the pH-responsive characteristic of H7K(R2)2 in MDA-MB-231 cell line in vitro and in vivo. The results of in vivo MRI and in vivo antitumor activity confirmed the theranostic effect of PTX/SPIO-SSL-H7K(R2)2 in MDA-MB-231 tumor-bearing model. Conclusion: Considering all our in vitro and in vivo results, we conclude that we developed targeting modified theranostic liposome which could achieve both role of antitumor and MRI. Keywords: tumor-specific pH-responsive peptide, paclitaxel, superparamagnetic iron oxide nanoparticles, liposome, theranostic efficiency

Yong Wang,1 Jie-Sen Zhou,1 Xu-Chen Xu,1 Zhou-Yang Li,1 Hai-Pin Chen,1 Song-Min Ying,1 Wen Li,1 Hua-Hao Shen,1,2 Zhi-Hua Chen1 1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 2State Key Laboratory of Respiratory Disease, Guangzhou, People’s Republic of China Introduction: Bronchial epithelial cell death and airway inflammation induced by cigarette smoke (CS) have been involved in the pathogenesis of COPD. GRP78, belonging to heat shock protein 70 family, has been implicated in cell death and inflammation, while little is known about its roles in COPD. Here, we demonstrate that GRP78 regulates CS-induced necroptosis and injury in bronchial epithelial cells.Materials and methods: GRP78 and necroptosis markers were examined in human bronchial epithelial (HBE) cell line, primary mouse tracheal epithelial cells, and mouse lungs. siRNA targeting GRP78 gene and necroptosis inhibitor were used. Expression of inflammatory cytokines, mucin MUC5AC, and related signaling pathways were detected.Results: Exposure to CS significantly increased the expression of GRP78 and necroptosis markers in HBE cell line, primary mouse tracheal epithelial cells, and mouse lungs. Inhibition of GRP78 significantly suppressed CS extract (CSE)-induced necroptosis. Furthermore, GRP78–necroptosis cooperatively regulated CSE-induced inflammatory cytokines such as interleukin 6 (IL6), IL8, and mucin MUC5AC in HBE cells, likely through the activation of nuclear factor (NF-κB) and activator protein 1 (AP-1) pathways, respectively.Conclusion: Taken together, our results demonstrate that GRP78 promotes CSE-induced inflammatory response and mucus hyperproduction in airway epithelial cells, likely through upregulation of necroptosis and subsequent activation of NF-κB and AP-1 pathways. Thus, inhibition of GRP78 and/or inhibition of necroptosis could be the effective therapeutic approaches for the treatment of COPD. Keywords: cigarette smoke, airway epithelium, glucose-regulated protein 78, necroptosis, airway injury

Zeyong Li,1,* Yuee Cai,2,* Yiqiao Zhao,1 Hua Yu,2 Haiyu Zhou,3 Meiwan Chen2 1Department of Laboratory Medicine, Guangdong No 2 Provincial People’s Hospital, Guangzhou, China; 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China; 3Department of Thoracic Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, South China University of Technology, Guangzhou, China *These authors contributed equally to this work Abstract: Mitoxantrone (MIT) is an anticancer agent with photosensitive properties that is commonly used in various cancers. Multidrug resistance (MDR) effect has been an obstacle to using MIT for cancer therapy. Photochemical internalization, on account of photodynamic therapy, has been applied to improve the therapeutic effect of cancers with MDR effect. In this study, an MIT-poly(ε-caprolactone)-pluronic F68-poly(ε-caprolactone)/poly(D,L-lactide-co-glycolide)–poly(ethylene glycol)–poly(D,L-lactide-co-glycolide) (MIT-PFP/PPP) mixed micelles system was applied to reverse the effect of MDR in MCF-7/ADR cells via photochemical reaction when exposed to near-infrared light. MIT-PFP/PPP mixed micelles showed effective interaction with near-infrared light at the wavelength of 660 nm and exerted great cytotoxicity in MCF-7/ADR cells with irradiation. Furthermore, MIT-PFP/PPP mixed micelles could improve reactive oxygen species (ROS) levels, decrease P-glycoprotein activity, and increase the cellular uptake of drugs with improved intracellular drug concentrations, which induced cell apoptosis in MCF-7/ADR cells under irradiation, despite MDR effect, as indicated by the increased level of cleaved poly ADP-ribose polymerase. These findings suggested that MIT-PFP/PPP mixed micelles may become a promising strategy to effectively reverse the MDR effect via photodynamic therapy in breast cancer. Keywords: mitoxantrone, polymeric mixed micelles, multidrug resistance, photodynamic therapy, breast cancer

Hai-Fei Chen,* Bin-Xian Xu, Hong-Shi Shen,* Zheng-Yang Li, Ling-Juan Jin, Jie-Qing Tang, Jing Wang, Jing-Jing Zhu, Long-Mei Qin, Qing-Ya Cui, Yong-Ya Ren, Tian-Qin Wu Department of hematology, 100th hospital of People’s Liberation Army, Suzhou, Jiangsu province, The People’s Republic of China *These authors have contributed equally to this paper Objective: To investigate the clinical characteristics of seronegative hepatitis-associated aplastic anemia (AA) (SNHAA) and hepatitis B virus (HBV) infection complicating AA (HBVAA), and thereby compare the efficacy of immunosuppressive therapy (IST).Methods: An analysis was conducted on the clinical data of ten patients with SNHAA out of 332 cases of AA from our center at AA diagnosis, and on the efficacy of IST. This was compared to 22 cases of HBVAA at AA onset as well as the associated IST outcomes.Results: Nine patients with SNHAA developed severe aplastic anemia, with a median age of 18 years. After IST, six (60%) of the SNHAA patients achieved complete remission and two achieved partial remission. The patients with HBVAA had a total response rate of 82.3%. The disease recurred in two HBVAA patients. No statistically significant differences were observed in response rate, mortality, and recurrence rate between both groups. As compared with HBVAA, patients with SNHAA had a shorter interval from the acute episode of hepatitis to AA onset (4 months versus 92 months, P=0.00), a quicker response to IST (2.5 months versus 4.5 months, P=0.018), a lower proportion of bone marrow hematopoietic tissues (20.6% versus 23.6%, P=0.03), and lower white blood cell and absolute neutrophil count (0.8×109/L versus 1.23×109/L and 0.26×109/L versus 0.58×109/L, P=0.026 and P=0.0009, respectively). No significant liver damage or hepatitis B fulminant infection was observed in either group during the follow-up. Conclusion: The prevalence of SNHAA is 3.01%. SNHAA often presents as severe AA and responds to IST quickly. Neither hepatitis prior to AA nor AA complicating HBV infection have been shown to influence the early efficacy of IST and adverse events, and HBV may not be the causative agent of AA. Keywords: hepatitis-associated aplastic anemia, hepatitis B infection, liver injury

Hai-Fei Chen,1,2 Li-Ping Xu,1 Zhi-Yong Luo,1 Zi-Qiang Yu,2 Zheng-Yang Li,1 Qing-Ya Cui,1 Long-Mei Qin,1 Yong-Ya Ren,1 Hong-Shi Shen,1 Jie-Qing Tang,1 Ling-Juan Jin,1 Jing-Jing Zhu,1 Jing Wang,1 Ke-Yuan Wang,1 Tian-Qin Wu,1 Zhao-Yue Wang21Department of Hematology, 100th Hospital of People's Liberation Army, 2Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, People's Republic of ChinaAbstract: A 41-year-old male had suffered from gradual hearing loss in his right ear for 2 years. Head computed tomography and magnetic resonance imaging scans showed a neoplasm in the cerebellopontine angle region, which was confirmed by the diagnosis of acoustic neurilemmoma by pathological findings after surgery. Following surgery, he routinely received valproic acid (VPA) to prevent seizures. However, the patient presented with hypofibrinogenemia and cerebral hemorrhage after taking VPA for 12 days. The hypofibrinogenemia recurred when VPA was re-administered. After withdrawal of VPA, his fibrinogen concentration rose to normal within several days. As far as we are aware, this is the first case of cerebral hemorrhage due to VPA to have been reported. Herein, as well as reporting on this case, a mini review of the relevant literature is also presented.Keywords: side effect, hypofibrinogenemia, cerebral hemorrhage, cerebellopontine angle, neoplasm

Hua-shan Shi1,* Xiang Gao,1,3,* Dan Li,1,* Qiong-wen Zhang,1 Yong-sheng Wang,2 Yu Zheng,1 Lu-Lu Cai,1 Ren-ming Zhong,2 Ao Rui,1 Zhi-yong Li,1 Hao Zheng,1 Xian-cheng Chen,1 Li-juan Chen,11State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China; 2State Key Laboratory of Biotherapy and Department of Thoracic Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China; 3Deparment of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, People's Republic of China*These authors contributed equally to this workAbstract: Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.Keywords: liposomes, curcumin, lung cancer