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Mengcao Weng,1,&ast; Dongdong Wang,2,&ast; Jia Zhong,2 Minyue Qian,1 Kai Zhang,2 Yue Jin1 1Department of Anesthesiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Jin, Department of Anesthesiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Rd, Hangzhou, Zhejiang, 310052, People’s Republic of China, Tel +8613456912018, Email yue_jin@zju.edu.cn Kai Zhang, Department of Anesthesiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Wenyixi Road 1367, Hangzhou, 311121, People’s Republic of China, Tel +8615858281107, Email comezk@zju.edu.cnPurpose: This study aimed to establish the 95% effective dose (ED95) of esketamine in combination with propofol for hysteroscopy and then to evaluate its efficacy and safety profile.Patients and Methods: This prospective, double-blind, randomized controlled trial consisted of two cohorts. In cohort 1, 45 women aged 18– 65 years undergoing hysteroscopy were randomly assigned to either group E (esketamine + propofol) or group A (alfentanil + propofol). Dixon’s up-and-down method was used to determine the ED95 of esketamine and alfentanil. In cohort 2, 86 patients were randomized to group E and group A, with the calculated ED95 dose of the study drugs used for induction. The success rate of anesthesia using the ED95% dose, along with parameters related to anesthesia induction, recovery, and adverse events were also recorded.Results: The ED95 of esketamine was 0.254 mg/kg (95% CI: 0.214– 1.004), while that of alfentanil was 9.121 μg/kg (95% CI: 8.479– 13.364). The anesthesia success rate was 93.0% in group E and 95.2% in group A (p = 0.664). After resuscitation, both groups achieved a 100% success rate. The induction time was significantly shorter in group E (60.0 [55.0– 70.0] s) compared to group A (67.0 [61.0– 79.3] s) (p = 0.006). Group E had lower rates of respiratory depression (p < 0.001), hypoxia (p = 0.006), minimum perioperative SpO2 (p = 0.010), and hypotension (p = 0.001). Esketamine had less effect on respiratory rate, heart rate, mean blood pressure, and end-tidal carbon dioxide compared to alfentanil (all p < 0.001). There were no significant differences in postoperative pain between the two groups.Conclusion: This study determined the ED 95 dose of esketamine for intravenous general anesthesia during hysteroscopy. Esketamine showed less respiratory and hemodynamic depression, as well as fewer adverse effects compared to alfentanil. Esketamine is an ideal anesthetic agent compared to alfentanil for hysteroscopic anesthesia.Trial Registration: www.chictr.org.cn, (ChiCTR2300077283); registered November 3, 2023.Keywords: esketamine, 95% effective dose, hysteroscopy, propofol

Xinjian Kang,1,2 Man Qian,3 Mingli Liu,2 Haiwei Xu,4 Baoshan Xu4 1Department of Orthopedics, Traditional Chinese Medicine Hospital of Qinhuangdao, Qinhuangdao, Hebei, People’s Republic of China; 2Tianjin Medical University, Graduate School, Tianjin, People’s Republic of China; 3Department of Refractive Surgery, Qinhuangdao Aier Ophthalmic Hospital, Qinhuangdao, Hebei, People’s Republic of China; 4Department of Minimally Invasive Spine Surgery, Tianjin Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Baoshan Xu, Department of Minimally Invasive Spine Surgery, Tianjin Hospital, No. 406 Jiefangnan Road, Hexi District, Tianjin, People’s Republic of China, Tel +86 13502028198, Fax +86- 22 -28241184, Email baoshanxu99@tmu.edu.cnPurpose: To explore the predictive factors of neck pain (NP) in patients with cervical degenerative disease by retrospectively analyzing their occupational and demographic characteristics and to provide a valuable reference for preventing and treating chronic NP.Patients and Methods: We retrospectively reviewed the occupational and demographic data of patients with cervical degenerative disease who had undergone anterior cervical surgery between June 2021 and December 2022 at our center. The patients were divided into NP and no-NP groups based on whether they had chronic NP before surgery. Relevant occupational and demographic data from all patients were statistically analyzed, and all variables were made categorical. Forward stepwise logistic regression models were constructed for preoperative chronic neck pain to explore the possible risk factors associated with chronic neck pain.Results: The differences in smoking, being an office worker, BMI, and disease types between NP and no-NP groups were statistically significant. In contrast, there were no statistically significant in age, sex, academic level, duration, and degeneration grade between the two groups. Moreover, further logistic regression analysis indicated that smoking, being an office worker, having an abnormal BMI, and cervical spondylotic radiculopathy (CSR) were related to chronic neck pain.Conclusion: The present study indicated that smoking, being an office worker, having an abnormal BMI, and CSR were predisposing risk factors for NP associated with cervical degenerative disease. Although intervertebral disc degeneration is the pathology basis of NP, the degeneration grade was not related to the occurrence of NP in our current study. Therefore, quitting smoking, avoiding sedentariness, and maintaining a normal BMI may prevent NP to some extent.Keywords: discogenic pain, radiating pain, musculoskeletal disorder, intervertebral disc degeneration

Min Wu,1 Shuo Feng,1 Meng Qian,2 Song Wang,3 Kaiguang Zhang1 1Department of Gastroenterology, Affiliated Provincial Hospital, Anhui Medical University, Anhui, People’s Republic of China; 2Graduate School of Bengbu Medical College, Anhui, People’s Republic of China; 3Department of Gastroenterology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, People’s Republic of ChinaCorrespondence: Kaiguang Zhang, Department of Gastroenterology, Affiliated Provincial Hospital, Anhui Medical University, Anhui, People’s Republic of China, Email zhangkaiguang@ustc.edu.cn Song Wang, Department of Gastroenterology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, People’s Republic of China, Email drwangsong@163.comPurpose: Helicobacter pylori (H. pylori) infection is a high-risk factor for gastric cancer (GC). The main aim of this study was to evaluate the effect of H. pylori on gastritis staging systems and the value of H. pylori combined with gastritis staging systems in predicting GC risk.Patients and Methods: This study enrolled 609 patients with gastric atrophy (GA) and 527 patients with gastric intestinal metaplasia (GIM), who were graded by the OLGA and OLGIM staging systems, respectively. Each individual underwent serum pepsinogen (PG) test, H. pylori detection and questionnaire investigation. We did a real-world retrospective follow-up survey for them in April 2022.Results: Compared with H. pylori-negative patients, H. pylori-positive patients had higher serum PGs/gastrin-17 (G-17) levels and lower PGR levels, regardless of OLGA/OLGIM stages I–II or III–IV. Furthermore, eight patients with atrophic gastritis who progressed to GC were previously in OLGA stages III–IV and OLGIM stages II–IV. The average duration of this process was 2.19± 1.03 years. Logistic regression analysis indicated that PGI and H. pylori infection were independent risk factors of individuals with OLGA stages III–IV. Age and PGR were independent risk factors of patients with OLGIM stages III–IV. PGI and PGR had good clinical diagnostic values for OLGA stages III–IV and OLGIM stages III–IV, respectively.Conclusion: Patients with OLGA/OLGIM stages III–IV should undergo endoscopic surveillance regardless of H. pylori infection. H. pylori-positive patients with OLGIM stage II also have a high risk of GC. H. pylori combined with PGI and PGR is helpful to evaluate the severity of chronic gastritis.Keywords: atrophy, metaplasia, Helicobacter pylori, gastric cancer, risk factors

Ping Guo1,2 &ast;, Yu Fang1 &ast;, Min Feng,1 Yue Shen,1 Shengliang Yang,1 Shikai Wang,1 Mincai Qian1 1Department of Psychosomatic Medicine, Huzhou Third Municipal Hospital, Huzhou, People’s Republic of China; 2Huzhou Third Municipal Hospital Affiliated with Huzhou University, Huzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shikai Wang; Mincai Qian, Department of Psychosomatic Medicine, Huzhou Third Municipal Hospital, No. 2088 in Tiaoxi East Road, Wuxing District, Huzhou, Zhejiang Province, 313000, People’s Republic of China, Tel +86 13665752769 ; +86 13757289002, Email wang_shikaii@163.com; 1311956613@qq.comObjective: To investigate the circadian rhythms of patients with major depressive disorder (MDD) pre-treatment and post-treatment to analyse possible influencing factors.Methods: In this study, we recruited 154 patients in the acute phase of MDD from 10 psychiatric centers in the province. The patients were divided into a morning chronotype group (16– 41 points), an intermediate chronotype group (42– 58 points) and an evening chronotype group (59– 86 points), according to the total scores obtained from the morningness–eveningness questionnaire (MEQ). They were treated randomly with antidepressants, either selective serotonin reuptake inhibitors or agomelatine, for 12 weeks and were evaluated using the MEQ, the 17-item Hamilton Depression Rating Scale (HAMD-17), the Hamilton anxiety scale, the Snaith–Hamilton pleasure scale (SHAPS), the multidimensional fatigue inventory (MFI-20) and the Pittsburgh sleep quality index at the baseline and then at 2, 4, 8 and 12 weeks. The results were analysed by Logistic regression analysis and repeated-measures analysis of variance.Results: The baseline detection rates for the evening, intermediate and morning types were 14.93%, 56.5% and 28.57%, respectively. HAMD-17 scores were significantly lower at weeks 2, 4, 8, and 12 after treatment in patients with different concurrent phenotypes compared with those before treatment (P< 0.05). There were significant differences in gender, age, body mass index, whether depression was first-episode, type of medication, baseline-MEQ and baseline-SHAPS in the chronotype change group compared with the post-treatment chronotype unchanged group (p< 0.05). Logistic regression analysis showed that medication type (P=0.047), baseline MEQ (P=0.001) and baseline SHAPS (P=0.001) were risk factors for improvement in circadian rhythm after treatment for depression.Conclusion: Circadian rhythm disturbances can be adjusted to a normal pattern with effective antidepressant therapy. The medication type, baseline MEQ and baseline SHAPS scores were the influencing factors for the recovery of circadian rhythm disorders.Keywords: major depressive disorder, morningness–eveningness questionnaire, circadian rhythm, chronotype, antidepressant

Abstract Background Incremental value (IncV) evaluates the performance change between an existing risk model and a new model. Different IncV metrics do not always agree with each other. For example, compared with a prescribed-dose model, an ovarian-dose model for predicting acute ovarian failure has a slightly lower area under the receiver operating characteristic curve (AUC) but increases the area under the precision-recall curve (AP) by 48%. This phenomenon of disagreement is not uncommon, and can create confusion when assessing whether the added information improves the model prediction accuracy. Methods In this article, we examine the analytical connections and differences between the AUC IncV (ΔAUC) and AP IncV (ΔAP). We also compare the true values of these two IncV metrics in a numerical study. Additionally, as both are semi-proper scoring rules, we compare them with a strictly proper scoring rule: the IncV of the scaled Brier score (ΔsBrS) in the numerical study. Results We demonstrate that ΔAUC and ΔAP are both weighted averages of the changes (from the existing model to the new one) in separating the risk score distributions between events and non-events. However, ΔAP assigns heavier weights to the changes in higher-risk regions, whereas ΔAUC weights the changes equally. Due to this difference, the two IncV metrics can disagree, and the numerical study shows that their disagreement becomes more pronounced as the event rate decreases. In the numerical study, we also find that ΔAP has a wide range, from negative to positive, but the range of ΔAUC is much smaller. In addition, ΔAP and ΔsBrS are highly consistent, but ΔAUC is negatively correlated with ΔsBrS and ΔAP when the event rate is low. Conclusions ΔAUC treats the wins and losses of a new risk model equally across different risk regions. When neither the existing or new model is the true model, this equality could attenuate a superior performance of the new model for a sub-region. In contrast, ΔAP accentuates the change in the prediction accuracy for higher-risk regions.

Shasha Cui,1,* Yujun Jiang,2,* Qianyu Shi,1,* Lei Zhang,3 Dehua Kong,4 Meijuan Qian,1 Jing Chu3 1Department of Nursing, Nantong Health College of Jiangsu Province, Nantong City, Jiangsu Province, People’s Republic of China; 2Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province, People’s Republic of China; 3Department of Nursing, Navy Medical University, Shanghai, People’s Republic of China; 4Department of Nursing, The 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Lanzhou City, Gansu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing ChuDepartment of Nursing, Navy Medical University, 800 Xiang Yin Road, Shanghai, 200433, People’s Republic of ChinaTel +86-21-8187 1483Email chujing1999@smmu.edu.cnMeijuan QianDepartment of Nursing, Nantong Health College of Jiangsu Province, 288 Zhen Xing Dong Road, Nantong City, Jiangsu Province, People’s Republic of ChinaEmail 158142474@qq.comBackground: During the Coronavirus Disease 2019 (COVID-19) pandemic, emergency departments and fever clinics nurses acted as gatekeepers to the health care system. To manage the psychological problems that these nurses experience, we should develop appropriate training and intervention programs.Objective: To identify the impact of COVID-19 on the psychology of Chinese nurses in emergency departments and fever clinics and to identify associated factors.Methods: This online cross-sectional study recruited participants through snowball sampling between 13 February and 20 February 2020. Nurses self-administered the online questionnaires, including a general information questionnaire, the Self-Rating Anxiety Scale, the Perceived Stress Scale-14, and the Simplified Coping Style Questionnaire.Results: We obtained 481 responses, of which 453 were valid, an effective response rate of 94.18%. Participants who had the following characteristics had more mental health problems: female gender, fear of infection among family members, regretting being a nurse, less rest time, more night shifts, having children, lack of confidence in fighting transmission, not having emergency protection training, and negative professional attitude.Conclusion: Effective measures are necessary to preserve mental health of nurses in emergency departments and fever clinics. These include strengthening protective training, reducing night shifts, ensuring adequate rest time, and timely updating the latest pandemic situation.Keywords: COVID-19, nurses, psychological health, mental health, stress, anxiety

Li-Hong Pan,1,* Ming Qian,1,* Weihua Qu,2 Qin Tang,2 Yuzhong Yan3 1Department of Psychiatry, Shanghai Pudong Nanhui Mental Health Center, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Shanghai Prison General Hospital, Shanghai, People’s Republic of China; 3Department of Research, Shanghai University of Medicine and Health Science Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuzhong Yan Email jykwsw@126.comBackground: Serum levels of C-reactive protein (CRP) were measured in patients with deficit schizophrenia (DS) to confirm the association between CRP level and cognitive performance and to determine whether CRP was a new biological indicator with the potential clinical applications in DS patients.Methods: Three independent samples [41 DS and 50 non-deficit schizophrenia (NDS) and 30 sex- and age-matched healthy controls (HCs)] were recruited in our study. Serum CRP levels were measured by immunofluorescence. The Positive and Negative Syndrome Scale (PANSS) and alternative forms of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were also assessed. And the relationships between serum CRP levels and both PANSS and RBANS scores were finally analyzed.Results: The results of serum CRP level were showed significantly different among the three groups and increased from the HCs to NDS patients to DS patients. There were also significant differences in the cognitive subdomain analyses among the three groups. Serum CRP levels were found positively correlated with total and negative PANSS scores, and showed negatively correlated with overall cognitive test scores in the DS samples.Conclusion: Serum C-reactive protein levels and their association with cognitive performance were different between deficit schizophrenia and non-deficit schizophrenia samples, and higher serum CRP level was associated with worse cognitive performance in the DS patients. The results indicated that CRP could be a potential biomarker, and DS could be a distinct subset of schizophrenia.Keywords: schizophrenia, deficit schizophrenia, C-reactive protein, inflammation, cognitive impairment

Meichen Qian,1 Na Wu,1,2 Ling Li,1 Wenshu Yu,1 Hong Ouyang,1 Xinyan Liu,1 Yujing He,1 Abdulrahman Al-Mureish2 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; 2Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of ChinaCorrespondence: Na WuDepartment of Endocrinology, Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of ChinaEmail 3441535223@qq.comAbstract: Ketone bodies are one of the products of fat metabolism which can be used as an alternative energy source for the human body in states of glucose deficiency. Normal pregnant women may develop ketosis due to physiological changes during pregnancy, while pregnant women with abnormal glucose metabolism are more likely to develop ketosis due to abnormal insulin secretion. Animal experiments and clinical studies have shown that exposure to high-ketone environments during pregnancy is closely related to adverse maternal and infant outcomes. However, there is no unified conclusion on whether ketone bodies should be routinely monitored during pregnancy. This review summarizes the existing studies on ketone body levels and pregnancy outcomes in the case of abnormal blood glucose during pregnancy, elaborates the current guidelines on the level of ketone bodies, provides the detection and treatment of ketosis in pregnant women with abnormal blood glucose in the clinical practice.Keywords: diabetic ketoacidosis, gestational diabetes mellitus, ketoacidosis, pregestational diabetes mellitus, diabetes mellitus

Qiang Zhang,1,2,* Fei Shen,1,2,* WenQing Shen,1,2 Jie Xia,1,2 Jing Wang,1,2 Yu Zhao,1,3 Zhe Zhang,1,2 Yi Sun,1,2 Min Qian,4 ShuZhe Ding1,2 1Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, People’s Republic of China; 2School of Physical Education & Health, East China Normal University, Shanghai 200241, People’s Republic of China; 3Center for Physical Education, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, People’s Republic of China; 4Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, People’s Republic of China*These authors contributed equally to this workCorrespondence: ShuZhe Ding Tel +86 13601798505Email szding@tyxx.ecnu.edu.cnObjective: Ketogenic diet (KD) and high-intensity interval training (HIIT) have preclinical benefits for type 2 diabetes (Db). However, the health risks of long-term KD use in diabetes should be ascertained and prevented. We hypothesized that KD-induced liver fibrosis in type 2 diabetic mice could be ameliorated by HIIT.Methods: Streptozotocin-induced type 2 diabetic mice were divided into high-fat diet (HFD) control (Db+HFD+Sed), KD control (Db+KD+Sed), HFD coupled with HIIT (Db+HFD+HIIT), and KD coupled with HIIT (Db+KD+HIIT) groups (n=6, per group). Control mice were kept in sedentary (Sed), while HIIT group mice underwent 40-minute high-intensity interval training three alternate days per week. After 8-week intervention, the indicators of body weight and insulin resistance, oxidative stress markers, hepatic fibrosis, genetic and protein expression of related pathways were tested.Results: We found that fasting blood glucose level was reduced in the Db+HFD+HIIT, Db+KD+Sed, and Db+KD+HIIT groups. Insulin sensitivity was increased in diabetic mice of these groups, whereas ROS levels were decreased in mice that underwent HIIT. The immunohistochemical staining of liver, serum index, and hepatic parameters of diabetic mice in the KD group revealed liver fibrosis, which was significantly attenuated by HIIT. Besides, these effects of HIIT were the outcome of hepatic stellate cell’s inactivation, reduced protein expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases, and the inhibition of TGF-β 1/Smad signaling.Conclusion: KD had a profound fibrotic effect on the liver of type 2 diabetic mice, whereas HIIT ameliorated this effect. KD did not show any apparent benefit as far as glucose tolerance and homeostasis were concerned. Concisely, our results demonstrated that KD should be coupled with HIIT for the prevention and preclinical mitigation of type 2 diabetes.Keywords: diabetes, ketogenic diet, high-intensity interval training, hepatic fibrosis, ROS, TGF-β 1/Smad signal

Yujing He,1 Na Wu,1,2 Wenshu Yu,1 Ling Li,1 Hong OuYang,1 Xinyan Liu,1 Meichen Qian,1 A Al-Mureish1 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Na WuDepartment of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Heping District, Shenyang, Liaoning Province 110004, People’s Republic of ChinaTel +86 18940258445Email 3441535223@qq.comAbstract: Gestational diabetes mellitus (GDM) refers to different degrees of abnormal glucose metabolism during pregnancy, where blood glucose levels do not reach the level of overt diabetes, accounting for 80– 90% of pregnancy with hyperglycemia. Hyperglycemia affects the pregnancy process, leading to a series of adverse maternal outcomes that have a profound impact on the future of the offspring. The establishing of an appropriate GDM model will provide theoretical basis for study GDM pathogenesis involves, the choice of resonable drugs and the observation the disease trends and outcomes. At present, there are many methods for establishing experimental GDM animal models and animal choices. This paper examines the different GDM models and their induction methods.Keywords: gestational diabetes mellitus, animal model, chemical induction, high-sugar and high-fat diet, genetic manipulation

Wenshu Yu,1 Na Wu,1 Ling Li,1 Hong OuYang,1 Meichen Qian,1 Haitao Shen2 1Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, People’ s Republic of China; 2Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Na WuDepartment of Endocrinology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Heping District, Shenyang, Liaoning Province 110004, People’ s Republic of ChinaTel +86 18940258445Email 3441535223@qq.comAbstract: Gestational diabetes mellitus (GDM) is associated with many adverse obstetric outcomes and neonatal outcomes, including preeclampsia, Cesarean section, and macrosomia. Active screening and early diabetes control can reduce the occurrence of adverse outcomes. Glycosylated hemoglobin (HbA1c) only reflects average blood glucose levels, but not glycemic variability (GV). Studies have shown that GV can cause a series of adverse reactions, and good control of GV can reduce the incidence of adverse pregnancy outcomes in patients with GDM. In order to provide clinicians with a better basis for diagnosis and treatment, this study reviewed the measurement, evaluation, and control of GV, the importance of GV for patients with GDM, and correlations between GV and maternal and neonatal outcomes.Keywords: gestational diabetes mellitus, glycemic variability, outcomes, self-monitoring of blood glucose, continuous glucose monitoring

Xiaopeng Sun,1,2 Hao Xue,1,3 Ye Xiong,4 Rui Yu,5 Xiao Gao,1 Mingyu Qian,1 Shaobo Wang,1 Huizhi Wang,1 Jianye Xu,1 Zihang Chen,1 Lin Deng,1,3 Gang Li1,3 1Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012, People’s Republic of China; 2Department of Neurosurgery, Dezhou People’s Hospital, Dezhou, Shandong Province 253014, People’s Republic of China; 3Institute of Brain and Brain-Inspired Science, Shandong Provincial Key Laboratory of Brain Function Remodeling, Shandong University, Jinan, Shandong Province, People’s Republic of China; 4Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People’s Republic of China; 5Department of Neurosurgery, The Second Hospital of Shandong University, Jinan 250033, People’s Republic of ChinaCorrespondence: Gang Li; Lin DengDepartment of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012, People’s Republic of ChinaEmail ligangqiluhospital@163.com; denglinqilu@163.comPurpose: Glioma is the most common and lethal type of brain tumor. While GALE (UDP-galactose-4-epimerase) has been shown to be overexpressed in some kinds of cancers, its expression in gliomas has not been reported. MicroRNAs (miRNAs) function as tumor suppressors in many cancers, and online datasets can be used to predict whether GALE is regulated by miR-let-7i-5p. In this investigation, we explored the effect and regulatory mechanisms of GALE on glioblastoma growth via miR-let-7i-5p.Methods: We used a Cox proportional hazards model and publicly available datasets to examine the relationship between GALE and the survival rates of glioma patients. Bioinformatics predicted the targeting of GALE by miR-let-7i-5p. The proliferation, migration, cell cycle and apoptosis of human glioblastoma cells were assessed by relevant assays. We also demonstrated the effect of GALE on glioblastoma multiforme [GBM] tumor growth using an in vivo orthotopic xenograft model.Results: GALE was upregulated in human gliomas, especially in high-grade gliomas (e.g., GBM). An obvious decline in GALE expression was observed in human glioblastoma cell lines (U87 and U251) following treatment with a small interfering RNA (siRNA) targeting GALE or miR-let-7i-5p mimics. Knockdown of GALE or overexpression of miR-let-7i-5p (with miR-let-7i-5p mimics) inhibited U87 and U251 cell growth. miR-let-7i-5p significantly restrained the migration ability of human glioblastoma cells in vascular mimic (VM), wound healing and transwell assays, and GALE promoted glioblastoma growth in vivo.Conclusion: Our findings confirm that GALE plays an important role in promoting the development of human glioma and that GALE can be regulated by miR-let-7i-5p to inhibit human glioblastoma growth.Implications for cancer survivors: Our data show that cancer survivors have low GALE expression, which indicates that GALE may be a diagnostic biomarker and a promising therapeutic target in glioblastoma.Keywords: glioblastoma, GALE, miR-let-7i-5p, proliferation, migration

Viruses subvert macromolecular pathways in infected host cells to aid in viral gene amplification or to counteract innate immune responses. Roles for host-encoded, noncoding RNAs, including microRNAs, have been found to provide pro- and anti-viral functions. Recently, circular RNAs (circRNAs), that are generated by a nuclear back-splicing mechanism of pre-mRNAs, have been implicated to have roles in DNA virus-infected cells. This study examines the circular RNA landscape in uninfected and hepatitis C virus (HCV)-infected liver cells. Results showed that the abundances of distinct classes of circRNAs were up-regulated or down-regulated in infected cells. Identified circRNAs displayed pro-viral effects. One particular up-regulated circRNA, circPSD3, displayed a very pronounced effect on viral RNA abundances in both hepatitis C virus- and Dengue virus-infected cells. Though circPSD3 has been shown to bind factor eIF4A3 that modulates the cellular nonsense-mediated decay (NMD) pathway, circPSD3 regulates RNA amplification in a pro-viral manner at a post-translational step, while eIF4A3 exhibits the anti-viral property of the NMD pathway. Findings from the global analyses of the circular RNA landscape argue that pro-, and likely, anti-viral functions are executed by circRNAs that modulate viral gene expression as well as host pathways. Because of their long half-lives, circRNAs likely play hitherto unknown, important roles in viral pathogenesis.

Providing accurate and dynamic age-specific risk prediction is a crucial step in precision medicine. In this manuscript, we introduce an approach for estimating the τ-year age-specific absolute risk directly via a flexible varying coefficient model. The approach facilitates the utilisation of predictors varying over an individual's lifetime. By using a nonparametric inverse probability weighted kernel estimating equation, the age-specific effects of risk factors are estimated without requiring the specification of the functional form. The approach allows borrowing information across individuals of similar ages, and therefore provides a practical solution for situations where the longitudinal information is only measured sparsely. We evaluate the performance of the proposed estimation and inference procedures with numerical studies, and make comparisons with existing methods in the literature. We illustrate the performance of our proposed approach by developing a dynamic prediction model using data from the Framingham Study.

Mengke Qian,1 Zhicen Lu,1 Chen Chen,2 Huaiqin Zhang,1 Haifeng Xie1 1Department of Prosthodontics, 2Department of Endodontics, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People’s Republic of China Abstract: Creating an alkaline environment prior to 10-methacryloyloxydecyldihydrogen­phosphate (MDP) conditioning improves the resin bonding of zirconia. The present study evaluated the effects of four alkaline coatings with different water solubilities and pH values on resin bonding of MDP-conditioned zirconia. Two alkaline nanoparticle coatings were studied in particular. Thermodynamics calculations were performed to evaluate the strengths of MDP-tetragonal phase zirconia chemical bonds at different pH values. Zirconia surfaces with and without alkaline coatings were characterized by scanning electron microscope (SEM)/energy dispersive spectrometer and Fourier transform infrared spectroscopy; alkaline coatings included NaOH, Ca(OH)2, nano-MgO, and nano-Zr(OH)4. A shear bond strength (SBS) test was performed to evaluate the effects of the four alkaline coatings on bonding; the alkaline coatings were applied to the surfaces prior to conditioning the zirconia with MDP-containing primers. Gibbs free energies of the MDP-tetragonal zirconia crystal model coordination reaction in different pH environments were -583.892 (NaOH), -569.048 [Ca(OH)2], -547.393 (MgO), and -530.279 kJ/mol [Zr(OH)4]. Thermodynamic calculations indicated that the alkaline coatings improved bonding in the following order: NaOH > Ca(OH)2 > MgO > Zr(OH)4. Statistical analysis of SBS tests showed a different result. SBSs were significantly different in groups that had different alkaline coatings, but it was not influenced by different primers. All four alkaline coatings increased SBS compared to control groups. Of the four coatings, nano-Zr(OH)4 and -MgO showed higher SBS. Therefore, preparing nano-Zr(OH)4 or -MgO coatings prior to conditioning with MDP-containing primers may potentially improve resin bonding of zirconia in the clinic. Keywords: adhesion, T-YZP, zirconia primer, bond strength, surface conditioning, MDP