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Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis during chronic stress is essential for the pathogenesis of depression, and increased activity of cAMP response element binding protein (CREB)-regulated transcription co-activator 1 (CRTC1) in the paraventricular nucleus (PVN) plays a critical role. As a well-investigated microRNA (miRNA), miR-184 has two forms, miR-184-3p and miR-184-5p. Recently, miRNAs target genes predictive analysis and dual-luciferase reporter assays identified an inhibitory role of miR-184-3p on CRTC1 expression. Therefore, we speculated that miR-184-3p regulation was responsible for the effects of chronic stress on CRTC1 in the PVN. Various methods, including the chronic social defeat stress (CSDS) model of depression, behavioral tests, Western blotting, co-immunoprecipitation (Co-IP), quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence, and adeno-associated virus (AAV)-mediated gene transfer, were used. CSDS evidently downregulated the level of miR-184-3p, but not miR-184-5p, in the PVN. Genetic knockdown and pharmacological inhibition of miR-184-3p in the PVN induced various depressive-like symptoms (e.g., abnormal behaviors, HPA hyperactivity, enhanced CRTC1 function in PVN neurons, downregulation of hippocampal neurogenesis, and decreased brain-derived neurotrophic factor (BDNF) signaling) in naïve male C57BL/6J mice. In contrast, genetic overexpression and pharmacological activation of miR-184-3p in the PVN produced significant beneficial effects against CSDS. MiR-184-3p in the PVN was necessary for the antidepressant actions of two well-known SSRIs, fluoxetine and paroxetine. Collectively. miR-184-3p was also implicated in the neurobiology of depression and may be a viable target for novel antidepressants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Influenza A viruses (IAV) are dynamic and highly mutable respiratory pathogens that present persistent public health challenges. Inflammasomes, as components of the innate immune system, play a crucial role in the early detection and response to infections. They react to viral pathogens by triggering inflammation to promote immune defences and initiate repair mechanisms. While a strong response is necessary for early viral control, overactivation of inflammasomes can precipitate harmful hyperinflammatory responses, a defining characteristic observed during severe influenza infections. The Absent in Melanoma 2 (AIM2) inflammasome, traditionally recognised for its role as a DNA sensor, has recently been implicated in the response to RNA viruses, like IAV. Paradoxically, AIM2 deficiency has been linked to both enhanced and reduced vulnerability to IAV infection. This review synthesises the current understanding of AIM2 inflammasome activation during IAV and explores its clinical implications. Understanding the nuances of AIM2's involvement could unveil novel therapeutic avenues for mitigating severe influenza outcomes.

Background: A history of abdominal surgery is considered a contraindication for laparoscopic procedures. However, the advancements in laparoscopic instruments and techniques have facilitated the performance of increasingly intricate operations, even in patients with prior abdominal surgeries. ICG fluorescence imaging technology offers advantages in terms of convenient operation and clearer intraoperative bile duct imaging, as confirmed by numerous international clinical studies on its feasibility and safety. The application of ICG fluorescence imaging technology in repeat laparoscopic biliary surgery, however, lacks sufficient reports., Methods: The clinical data of patients who underwent elective reoperation of the biliary tract in our department between January 2020 and June 2022 were retrospectively analyzed. ICG was injected peripherally before the operation, and near-infrared light was used for 3-dimensional imaging of the bile duct during the operation., Results: Altogether, 143 patients were included in this study and divided into the fluorescence and nonfluorescence groups according to the inclusion criteria. Among the 26 patients in the fluorescence group, cholangiography was successfully performed in 24 cases, and the success rate of intraoperative biliary ICG fluorescence imaging was 92.31%. The intraoperative biliary tract identification time was significantly different between the fluorescence and nonfluorescence groups, but no statistical difference was observed in the final operation method, operative time, and intraoperative blood loss between the 2 groups. Although there was no significant difference in the postoperative ventilation rate, incidence of bile leakage, and stone recurrence rate at 6 months postoperatively between the 2 groups (P>0.05), a significant difference in postoperative hospitalization days was observed (P=0.032)., Conclusion: The application of ICG fluorescence imaging technology in laparoscopic reoperation of the biliary tract is useful for the early identification of the biliary tract during operation, thereby shortening the operative time and reducing the risk of damage to nonoperative areas. This approach also enhances the visualization of the biliary system and avoids secondary injury intraoperatively due to poor identification of the biliary system. This technique is safe for repeat biliary tract surgery and has a good application prospect., Competing Interests: The author declares no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The caudate lobe (S1) of the liver, due to its deep central position, presents a formidable challenge for laparoscopic resection. Historical skepticism about laparoscopic approaches has been overshadowed by advancements in technology and technique, with recent studies showing comparable outcomes to open surgery., Methods: This paper introduces the "Easy First" technique and the Sextet strategies for laparoscopic hepatic caudate lobectomy. The strategies include meticulous preoperative planning, optimal trocar placement, and team positioning, tailored to the anatomical complexities of the caudate lobe., Results: With a 0% conversion and mortality rate, our series demonstrates the safety of the "Easy First" technique. The Sextet strategies have been instrumental in navigating the technical challenges, emphasizing the importance of patient selection and surgeon expertise., Conclusion: The "Easy First" technique, with its structured approach and the Sextet strategies, offers a replicable method for laparoscopic caudate lobectomy. It underscores the need for stringent patient selection, advanced technical skill, and high-volume center expertise to ensure procedural success and patient safety., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Declaration of competing interest No any potential financial and non-financial conflicts of interest.

Background: The salt-inducible kinase 1 (SIK1)-CREB-regulated transcription co-activator 1 (CRTC1) system in the paraventricular nucleus (PVN) of the hypothalamus has been demonstrated to participate in not only depression neurobiology but also the antidepressant mechanisms of fluoxetine, paroxetine, venlafaxine, and duloxetine. Like fluoxetine and paroxetine, escitalopram is also a well-known selective serotonin (5-HT) reuptake inhibitor (SSRI). However, recently it has been found that escitalopram can modulate a lot of targets other than the 5-HT system. Here, we speculate that escitalopram produces effects on the SIK1-CRTC1 system in the PVN., Methods: Two mice models of depression (chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS)), various behavioral tests, enzyme linked immunosorbent assay (ELISA), western blotting, co-immunoprecipitation (Co-IP), quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence, and adeno-associated virus (AAV)-mediated gene transfer were used together in the present study., Results: It was found that escitalopram administration not only significantly prevented the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis induced by CSDS and CUMS, but also notably reversed the effects of CSDS and CUMS on SIK1, CRTC1, and CRTC1-CREB binding in the PVN of mice. AAV-based genetic knock-down of SIK1 in PVN neurons evidently abolished the antidepressant-like effects of escitalopram in mice., Limitation: A shortage of this study is that only rodent models of depression were used, while human samples were not included., Conclusions: In summary, regulating the SIK1-CRTC1 system in the PVN participates in the antidepressant mechanism of escitalopram, which extends the knowledge of the pharmacological actions of escitalopram., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background/aim: Laparoscopic hepatectomy has become a common management strategy for liver tumors owing to its less invasive nature and enhanced visual perspective. Yet, its use in the caudate lobe poses challenges. This study evaluates the experiences of patients who underwent laparoscopic hepatectomy for hepatic tumors in the caudate lobe and aims to propose strategies for performing such procedures., Methods: We retrospectively analyzed the clinical data of twelve patients who underwent laparoscopic hepatic caudate lobe resection at the Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Kunming Medical University., Results: All twelve laparoscopic procedures were successful, with none requiring conversion to open surgery. The surgical methods varied: five cases involved simple resection of the Spiegel lobe, one case involved total caudate lobe resection, three cases involved paravena cava lobe resection, and three cases involved resection of the caudate process. The operation time ranged from 49 to 319 min (mean, 219 min). Intraoperative blood loss ranged from 20 to 500 ml, averaging 194 ml. No patients needed blood transfusions during or after the operation, and there were no instances of postoperative bleeding, bile leakage, or abdominal infection., Conclusion: Given adequate control of hepatic inflow, sufficient exposure to the surgical field, and an appropriate approach, laparoscopic hepatectomy in the caudate lobe could potentially become a standard surgical technique., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the mechanism of electroacupuncture （EA） in promoting the browning of white adipose tissue in middle-aged and aged obese rats induced by high fat by regulating AMP-activated protein kinase （AMPK） /silence-information regulatory factor 1 （Sirt1） pathway and neuregulin 4 （Nrg4）., Methods: Twenty-four male SD rats were randomized into blank control, model and EA groups （ n =8 per group）. The obesity model was established by feeding the rats with high-fat diet for 6 weeks. For the EA group, EA （2 Hz/15 Hz, 1.5 mA） was applied to "Guanyuan" （CV4） and bilateral "Shenshu" （BL23）, "Fenglong" （ST40） and "Tianshu" （ST25） for 20 min, once a day, 5 days a week for 6 weeks. Rats of the blank control and model groups were also restrained for 20 min. The body mass and food intake were measured every week, and the Lee's index, epididymal fat, perirenal fat and brown adipose tissue were weighed. The contents of serum total cholesterol （TC）, triglyceride （TG）, high density lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol （LDL-C） and norepinephrine （NE） were determined by ELISA. H.E. staining was used to observe the morphological changes of white and brown adipose tissue. The mRNA expression levels of mitochondrial uncoupling protein 1 （UCP1）, peroxisome proliferator activated receptor γ co-activator 1 α （PGC-1 α ）, PR-domain protein 16 （PRDM16）, peroxisome proliferator activated receptor γ （PPARγ） and Nrg4 in the adipose tissue were detected by quantitative real time PCR, and the protein expression levels of Nrg4, AMPK α , Sirt1 and interleukin-6 （IL-6） in the white and brown adipose tissue were detected by Western blot., Results: Compared with the blank control group, the body mass, food intake, the Lee's index, epididymal fat and perirenal fat mass, and serum TG, TC and LDL-C contents and the expression level of IL-6 protein were significantly increased （ P <0.01, P <0.05, P <0.001）, and the brown adipose mass, serum HDL-C and NE contents, the expression levels of UCP1, PGC-1 α , PRDM16, PPARγ and Nrg4 mRNAs, and the protein expression levels of AMPK α , Sirt1 and Nrg4 proteins in both white and brown adipose tissues were significantly decreased in the model group （ P <0.01, P <0.05）. After EA intervention, the increased levels of body mass, food intake, Lee's index, epididymal fat and perirenal fat mass, serum TG, TC and LDL-C contents, and the expression of IL-6 protein, and the decreased levels of brown adipose mass, serum HDL-C and NE contents, expression levels of UCP1, PGC-1 α , PRDM16, PPARγ and Nrg4 mRNAs, and those of AMPK α , Sirt1 and Nrg4 proteins in both white and brown adipose tissues were apparently reversed（ P <0.05, P <0.01, P <0.001）. H.E. staining showed an increase of the volume and content of intracellular vacuoles of both white and brown adipose tissues, disordered arrangement of cells with vague boundary in the model group, which was relatively milder including a decrease of volume and content of vacuoles of both white and brown adipose, neat arrangement of cells with clear boundary., Conclusion: EA intervention can improve lipid metabolism and promote white adipose tissue browning in middle-aged and aged obese rats, which is possibly associated with its functions in activating AMPK/Sirt1 signaling pathway and up-regulating the level of Nrg4.

Theoretical models and empirical evidence suggest an association between volunteering and health outcomes in older adults. However, less is known about existing programs that involve older adults engaging in formal volunteering, especially programs for older volunteers with cognitive impairment. In this review, we summarized and evaluated different types of volunteering-based programs involving older volunteers with and without cognitive impairment. After a non-systematic literature search, we presented eight example volunteer programs. Older volunteers participate in the programs in person or remotely. In five of the programs, older volunteers without cognitive impairment participate in intergenerational engagement, support and referral, home visiting, and dementia care services. The other three programs specifically recruit older volunteers with cognitive impairment and provide intergenerational engagement and individualized volunteer activities. Both strengths and challenges identified in the programs were discussed. Different types of volunteering-based programs are available for engaging older volunteers. For volunteers to remain active during the pandemic or for volunteers who live with cognitive impairment, remote programs can be a valuable alternative. Program effects on older volunteers need to be tested in more rigorously designed studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Dong, Wu and Xu.)

Background: Sleep disturbance and neuropsychiatric symptoms are common clinical symptoms of cerebral small vessel disease (CSVD), but the underlying mechanism is unclear. Here, we investigated the relationship between sleep quality and neuropsychiatric performance in patients with CSVD., Methods: A total of 30 patients with CSVD and 35 healthy controls (HCs) were recruited. The 13-item Beck Depression Inventory (BDI-13), Beck Anxiety Inventory (BAI), and Symptom Check List 90 (SCL90) were used to assess depression, anxiety, and other psychological symptoms, respectively. Sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI), and cognitive function was tested using Montreal Cognitive Assessment (MoCA)., Results: When compared to the HC group, the patients with CSVD showed increased anxiety and neuropsychiatric symptoms, worse sleep quality, and impaired cognition ( p < 0.05). The prevalence of comorbid poor sleep quality in the patients with CSVD was approximately 46%. The patients with CSVD with poor sleep quality also had more severe neuropsychiatric symptoms. After controlling for demographic variables, sex and anxiety significantly predicted sleep quality., Conclusion: This study suggests that the prevalence of CSVD with poor sleep quality is high, and that sex and anxiety are independent risk factors for CSVD comorbid sleep quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Qin, Chen, Jiang, Tang, Wang, Xu, Xu and Yuan.)

Background: Non-suicidal self-injury (NSSI) in adolescents is a significant mental health problem around the world. Here, we performed a meta-analysis to systematically delineate the risk factors for NSSI., Method: We searched Medline, Embase, Web of Science and Cochrane for relevant articles and abstracts published prior to 12 November 2021. Pooled odds ratios (ORs) and 95% confident intervals (CIs) were used to assess various risk factors, and publication bias was assessed by Egger's test, the trim and fill method and meta-regression. This study is registered with PROSPERO, CRD42021265885., Results: A total of 25 articles were eventually included in the analysis. Eighty risk factors were identified and classified into 7 categories: mental disorders (ORs, 1·89; 95% CI, 1·60-2·24), bullying (ORs, 1·98; 95% CI, 1·32-2·95), low health literacy (ORs, 2·20; 95% CI, 1·63-2·96), problem behaviours (ORs, 2·36; 95% CI, 2·00-2·77), adverse childhood experiences (ORs, 2·49; 95% CI, 1·85-3.34), physical symptoms (ORs, 2·85; 95% CI, 1·36-5·97) and the female gender (ORs, 2·89; 95% CI, 2·43-3·43). The range of heterogeneity (I 2 ) was from 20·3% to 99·2%., Conclusion: This meta-analysis found that mental disorders, low health literacy, adverse childhood experiences, bullying, problem behaviours, the female gender and physical symptoms appear to be risk factors for NSSI., Competing Interests: All authors declare no competing interests., (© 2022 The Authors.)

As a highly prevalent neuropsychiatric disorder worldwide, the pathophysiology of depression is not yet fully understood and based on multiple factors among which chronic stress is critical. Numerous previous studies have shown the role of central mammalian target of rapamycin complex 1 (mTORC1) signaling in depression. However, so far it remains elusive by which way chronic stress down-regulates the activity of central mTORC1. Liver kinase b1 (LKB1) has been demonstrated to regulate the activity of the mTORC1 signaling cascade by phosphorylating AMP activated protein kinase (AMPK). Here, this study aimed to explore whether LKB1 participates in depression by regulating the downstream AMPK-mTORC1 signaling, and various methods including mouse models of depression, western blotting and immunofluorescence were used together. Our results showed that chronic stress significantly enhanced the expression of both phosphorylated LKB1 and total LKB1 in the medial prefrontal cortex (mPFC) but not the hippocampus. Furthermore, genetic knockdown of LKB1 in the mPFC fully reversed not only the depressive-like behaviors induced by chronic stress in mice but also the effects of chronic stress on the activity of AMPK and the mTORC1 system. Taken together, this study preliminarily suggests that LKB1 in the mPFC could be a feasible target for antidepressants. This study also provides support for the potential use of LKB1 inhibition strategies against the chronic stress-related neuropsychiatric disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Depression is one of the most common psychiatric diseases in the 21st century, while its pathogenesis is not yet fully understood. Currently, besides to the monoaminergic system, the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) signaling is one of the most attractive signaling pathways for treating depression. Mitogen and stress-activated kinase (MSK) 1 and 2 are nuclear proteins activated downstream of the ERK1/2 or p38 MAPK pathways, and it has been demonstrated that MSKs are involved in the BDNF-CREB signaling. Here we assumed that MSKs may play a role in depression, and various methods including the chronic social defeat stress (CSDS) model of depression, western blotting, immunofluorescence and virus-mediated gene transfer were used together. It was found that CSDS fully enhanced the expression of both phosphorylated MSK1 and total MSK1 in the hippocampus but not the medial prefrontal cortex (mPFC). CSDS did not influence the expression of phosphorylated MSK2 and total MSK2 in the two brain regions. Genetic over-expression of hippocampal MSK1 fully prevented not only the CSDS-induced depressive-like behaviors but also the CSDS-induced dysfunction in the hippocampal BDNF-CREB signaling and neurogenesis in mice, while genetic knockdown of hippocampal MSK1 aggravated the CSDS-induced depressive-like symptomatology in mice. Our results collectively suggest that although CSDS evidently enhances the activity of hippocampal MSK1, it is not a contributor to the CSDS-induced dysfunction in the brain but a defensive feedback regulator which protects against CSDS. Therefore, hippocampal MSK1 participates in the pathogenesis of depression and is a feasible and potential antidepressant target., (Copyright © 2021 Elsevier Inc. All rights reserved.)

As a widely-known neuropsychiatric disorder, the exact pathogenesis of depression remains elusive. MiRNA-206 (miR-206) is conventionally known as one of the myomiRs and has two forms: miR-206-3p and miR-206-5p. Recently, miR-206 has been demonstrated to regulate the biosynthesis of brain-derived neurotrophic factor (BDNF), a very popular target involved in depression and antidepressant responses. Here we assumed that miR-206 may play a role in depression, and various methods including the chronic social defeat stress (CSDS) model of depression, quantitative real-time reverse transcription PCR, western blotting, immuofluorescence and virus-mediated gene transfer were used together. It was found that CSDS robustly increased the level of miR-206-3p but not miR-206-5p in the hippocampus. Both genetic overexpression of hippocampal miR-206-3p and intranasal administration of AgomiR-206-3p induced not only notable depressive-like behaviors but also significantly decreased hippocampal BDNF signaling cascade and neurogenesis in naïve C57BL/6J mice. In contrast, both genetic knockdown of hippocampal miR-206-3p and intranasal administration of AntagomiR-206-3p produced significant antidepressant-like effects in the CSDS model of depression. Furthermore, it was found that the antidepressant-like effects induced by miR-206-3p inhibition require the hippocampal BDNF-TrkB system. Taken together, hippocampal miR-206-3p participates in the pathogenesis of depression by regulating BDNF biosynthesis and is a feasible antidepressant target., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Aims: The early prediction of the development of acute kidney injury (AKI) in critically ill patients with sepsis would facilitate early effective intervention. Recently, interest has focused on the biomarkers for AKI-linked iron metabolism. This study aimed to assess the early predictive values of hepcidin, neutrophil gelatinase-associated lipocalin (NGAL), and their combination for secondary AKI in patients with sepsis., Materials and Methods: A prospective cohort study was performed in septic patients. Serum and urine hepcidin, and urine NGAL were analyzed at admission. The primary outcome measure was occurrence of sepsis-induced AKI based on 2011 Kidney Disease: Improving Global Outcomes (KDIGO) criteria during the first week of ICU stay., Results: Of the 90 patients analyzed finally in the study, 44 (48.9%) patients developed AKI. Patients with AKI occurrence were more likely than those without AKI to have higher serum hepcidin and urine NGAL levels at admission (P < 0.01). Higher concentrations of these biomarkers were each independent predictor of the development of AKI in critically septic patients within the first week of their ICU stay. Serum hepcidin and urine NGAL (AUROC 0.787, 95% CI 0.688 to 0.8660 and AUROC 0.729, 95% CI 0.625 to 0.818, respectively) were comparable predictive indicators of AKI occurrence (P = 0.43 for DeLong's test). Combining both biomarkers increased the AUROC to 0.828(95% CI 0.733 to 0.899), and this performance was statistically significantly better than urine NGAL alone (P = 0.03 for DeLong's test)., Conclusion: Serum hepcidin measured at admission predicts the development of AKI similarly to urine NGAL. However, serum hepcidin adds significant accuracy to this prediction in combination with urine NGAL alone and has a good predictive value in patients with sepsis. Larger studies are needed to validate and explain these findings., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cognitive impairment has been identified as a core feature of depression. Serum triglycerides (TG), gonadal hormone and sex difference were shown to influence cognitive performance. The purpose of this study was to investigate the associations among serum TG, gonadal hormone, sex difference and cognitive performance in patients with major depressive disorders (MDD)., Methods: The enrolled 183 patients (male/female = 80/103) meeting DSM-IV criteria for MDD were divided into high TG group (patients-HTG) and normal TG group (patients-NTG) according to TG level. Serum TG, estradiol (E2) and testosterone (T) levels were measured by the glycerokinase peroxidase-peroxidase and chemiluminescence methods. Cognition was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The study was conducted between August 2016 and January 2020., Results: In female, patients-HTG had lower immediate memory, language, attention, delayed memory and RBANS total scores than patients-NTG after adjusting for covariates. There were significant differences in serum E2 and T levels between patients-HTG and patients-NTG in female after controlling for covariates. In female patients-HTG, serum E2 level was positively associated with immediate memory, delayed memory and RBANS total scores, and serum T level was positively related to immediate memory, language and RBANS total scores. These findings were not seen in male patients., Conclusions: Our data suggested that patients-HTG exhibited poorer cognitive function compared with patients-NTG in female. Moreover, the decline in serum gonadal hormone level might contribute to the high TG development of female MDD, and was further implicated in their cognitive decline., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Persistent acute kidney injury (AKI) has been shown to be closely associated with poor prognosis in critical patients. Recent studies have shown that procalcitonin (PCT) is valuable for the early prediction of AKI in critically patients. Our aim was to determine whether PCT and its kinetic changes could predict the occurrence of persistent AKI in critical patients., Methods: This is a prospective observational study. The definition of AKI was based on the Kidney Disease: Improving Global Outcomes criteria. Persistent AKI was defined as renal function that does not return to baseline serum creatinine levels within 48 h. Blood samples were obtained at the onset of AKI and two subsequent days of hospital stay. 24-h PCT change (ΔPCT-24 h) was defined as 24 h PCT minus baseline PCT (day 0)., Results: A total of 91 critical patients with AKI were included in this study. The persistent AKI group had a stepwise increase in PCT concentration. ΔPCT-24 h was higher in the persistent AKI group (p < .01). Logistic regression analysis showed that ΔPCT-24 h (p = .04) was independent predictors of persistent AKI. The receiver operating characteristic curves showed that area under the curve of ΔPCT-24 h was 0.84 (p < .01), and the cut-off value for PCT to predict persistent AKI was 0.56 ng/ml., Conclusion: Our study showed that the observation of kinetic changes in PCT is more significant for the early prediction of persistent AKI than the index of PCT at a single time point. ΔPCT-24 h is a good predictor of persistent AKI in critical patients., (© 2021 Asian Pacific Society of Nephrology.)

The clinical characteristics and risk factors of patients with coronavirus disease 2019 (COVID-19) with re-positive or false-negative test results have so far remained to be determined. The present study provides a cross-sectional observational study on 134 hospitalized patients selected from Huoshenshan Hospital (Wuhan, China) using cluster sampling. A total of 68 patients had reduced red blood cell (RBC) counts, 55 a decrease in the hemoglobin concentration (HBC) and 73 a decline in hematocrit (HCT). The false-negative rate of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA detection in pharyngeal swab specimens was 18.7%. The absolute lymphocyte count (ALC), RBC, HBC and HCT levels in false-negative patients were significantly higher than those in patients who tested positive for viral nucleic acids. Multivariate logistic regression analysis indicated that RBC [odds ratio (OR)=0.43, 95% CI: 0.18-0.99], HBC (OR=0.97, 95% CI: 0.94-0.99) and ALC (OR=0.43, 95% CI: 0.20-0.91) were the factors influencing the negative testing results for viral nucleic acid. The rate of re-positive patients was 16.4%. The white blood cell, RBC, HBC and HCT values in re-positive patients were lower than those in non-re-positive patients. The median (interquartile range) values for RBC, HBC and HCT of male re-positive patients were 3.95 (3.37, 4.2) x10 12 /l, 123 (103, 133) g/l and 36.6 (31.1, 39.2)%, respectively, while the RBC, HBC and HCT of female re-positive patients were 3.54 (3.13, 3.74) x10 12 /l, 115 (102, 118) g/l and 34.2 (28.5, 34.9)%, respectively. It was determined that RBC, HBC and HCT values had moderate accuracy in predicting SARS-CoV-2 recurrence in patients with COVID-19 using receiver operating curve analysis. The present study suggested that RBC may have an important role in the pathogenesis of COVID-19., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Jiang et al.)

Cognitive and sensory deficits were considered a core feature of major depressive disorder (MDD). However, few studies investigated stereopsis integrity in patients with MDD. Thus, the objectives of this study investigated stereopsis integrity and its correlations with cognitive function and depressive symptom in patients with MDD. 90 patients with MDD and 116 healthy controls (HCs) were enrolled in this study. Their stereoacuity was evaluated using the Titmus Stereopsis Test as well as assessing their cognitive function and depressive symptom by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Hamilton Depression Scale (HAMD). Log seconds of arc was significantly higher in patients than HCs (1.92 ± 0.41 versus 1.67 ± 0.16, t = 5.35, p < 0.0001). The percentage of patients with correct stereopsis detection was markedly declined in 400 (z = 3.06, p = 0.002), 200 (z = 3.84, p < 0.001), 140 (z = 4.73, p < 0.001), 100 (z = 4.58, p < 0.001), 80 (z = 5.06, p < 0.001), 60 (z = 4.72, p < 0.001), 50 (z = 4.24, p < 0.001), and 40 (z = 4.85, p < 0.001) seconds of arc compared with HCs. Log seconds of arc was significantly correlated with the RBANS total score (r = -0.38, p < 0.0001), subscores of attention (r = -0.49, p < 0.0001) and language (r = -0.33, p = 0.001) rather than HAMD score (r = 0.03, p = 0.78) in MDD patients. In addition, log seconds of arc was significantly related to the RBANS total score (r = -0.58, p < 0.0001) and language score (r = -0.45, p = 0.006) rather than attention score (r = -0.30, p = 0.07) in HCs. Further stepwise multivariate regression analyses showed the negative correlation of log seconds of arc with attention score (β = -0.80, t = -3.95, p < 0.0001) rather than HAMD score (β = -0.008, t = -0.09, p = 0.93) in MDD patients. However, there was no relationship between log seconds of arc and attention score in HCs (β = 1.52, t = 1.19, p = 0.24). Our results identified the marked deficits of stereopsis in MDD patients that were tightly correlated with their attention functioning rather than depressive symptom., (Copyright © 2021 Elsevier Inc. All rights reserved.)

As a well-known multimodal-acting antidepressant, vortioxetine is thought to aim at several serotonin (5-HT) receptors and the 5-HT transporter. However, recently more and more proteins besides 5-HT are being reported to participate in the antidepressant mechanism of vortioxetine. As a widely known nuclear hormone receptor, peroxisome proliferator activated receptor α (PPARα) possesses transcriptional activity and is very important in the brain. Several reports have suggested that hippocampal PPARα is implicated in antidepressant responses. Here we speculate that hippocampal PPARα may participate in the antidepressant mechanism of vortioxetine. In this study, chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS), behavioral tests, the western blotting and adenovirus associated virus (AAV)-mediated gene knockdown methods were used together. It was found that vortioxetine administration significantly reversed the inhibitory actions of both CUMS and CSDS on the hippocampal PPARα expression. Pharmacological blockade of PPARα notably prevented the antidepressant actions of vortioxetine in the CUMS and CSDS models. Moreover, genetic knockdown of PPARα in the hippocampus also significantly blocked the protecting effects of vortioxetine against both CUMS and CSDS. Therefore, the antidepressant effects of vortioxetine in mice require hippocampal PPARα., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Gu, Liu, Liu, Tang, Ji, Guan, Zhao, Sun, Xu and Jiang.)

Purpose: Acute kidney injury (AKI) is a common complication of sepsis and has high mortality. The 2017 Acute Disease Quality Initiative (AQDI) workgroup proposed new definitions for AKI - transient AKI and persistent AKI; however, very little is known about the effect of transient and persistent septic AKI on short-term mortality among critically ill patients with sepsis. The purpose of this study was to assess the impact of persistent AKI on mortality and to evaluate whether serum hepcidin can predict the occurrence of persistent AKI in critically ill patients with sepsis., Materials and Methods: This prospective observational study was performed in a general hospital mixed surgical-medical ICU in Pudong, China. Consecutive adults with sepsis admitted to the ICU with absence of chronic kidney disease, renal transplant, and AKI were included. AKI was defined according to the KDIGO criteria and classified as transient (&lt; 48-hour duration) or persistent (48-hour duration). Blood samples were obtained within 6 hours from when AKI was diagnosed., Results: A total of 90 patients with sepsis or septic shock were included in the analysis. 44 (48.89%) patients developed AKI during ICU stay: 20 (45.45%) had transient and 24 (54.55%) had persistent AKI. Persistent AKI has a higher mortality than transient AKI (66.7 vs. 30.0%, p = 0.002). Persistent AKI and sequential organ failure assessment (SOFA) scores were an independent predictor of 60-day mortality. Patients with persistent AKI had higher concentrations of serum creatinine (SCr) and hepcidin than transient AKI patients when AKI was diagnosed. Logistic regression indicated that serum hepcidin was an independent predictor of persistent AKI in septic patients, with a fairly predictive value (AUC 0.71, 95% CI: 0.47 - 0.87; p = 0.02)., Conclusion: Persistent AKI was associated with increased 60-day mortality compared with transient AKI in septic patients. The serum hepcidin levels measured when AKI was diagnosed have a fair predictive value to predict the occurrence of persistent AKI in septic patients.

Marsdeniae tenacissimae Caulis is a traditional Chinese medicine, named Tongguanteng (TGT), that is often used for the adjuvant treatment of cancer. In our previous study, we reported that an ethyl acetate extract of TGT had inhibitory effects against adenocarcinoma A549 cells growth. To identify the components of TGT with anti-tumor activity and to elucidate their underlying mechanisms of action, we developed a technique for isolating compounds, which was then followed by cytotoxicity screening, network pharmacology analysis, and cellular and molecular experiments. We isolated a total of 19 compounds from a TGT ethyl acetate extract. Two novel steroidal saponins were assessed using an ultra-performance liquid chromatography-photodiode array coupled with quadrupole time-of-flight mass (UPLC-ESI-Q/TOF-MS). Then, we screened these constituents for anti-cancer activity against non-small cell lung cancer (NSCLC) in vitro and obtained six target compounds. Furthermore, a compound-target-pathway network of these six bioactive ingredients was constructed to elucidate the potential pathways that controlled anticancer effects. Approximately 205 putative targets that were associated with TGT, as well as 270 putative targets that were related to NSCLC, were obtained from online databases and target prediction software. Protein-protein interaction networks for drugs as well as disease putative targets were generated, and 18 candidate targets were detected based on topological features. In addition, pathway enrichment analysis was performed to identify related pathways, including PI3K/AKT, VEGF, and EGFR tyrosine kinase inhibitor resistance, which are all related to metabolic processes and intrinsic apoptotic pathways involving reactive oxygen species (ROS). Then, various cellular experiments were conducted to validate drug-target mechanisms that had been predicted using network pharmacology analysis. The experimental results showed the four C21 steroidal saponins could upregulate Bax and downregulate Bcl-2 expression, thereby changing the mitochondrial membrane potential, producing ROS, and releasing cytochrome C, which finally activated caspase-3, caspase-9, and caspase-8, all of which induced apoptosis in A549 cells. In addition, these components also downregulated the expression of MMP-2 and MMP-9 proteins, further weakening their degradation of extracellular matrix components and type IV collagen, and inhibiting the migration and invasion of A549 cells. Our study elucidated the chemical composition and underlying anti-tumor mechanism of TGT , which may be utilized in the treatment of lung cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Xu, Li, Wang, Hu, Shi, Li, Huang, Kang and Liu.)

Background: The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors., Method: This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students' choices of psychiatry at matriculation and as a career., Results: 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87-2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28-3.08), being female (OR = 1.50, 95% CI = 1.30-1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28-1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08-1.46) correlated positively with students' choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29-0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63-0.97) were less likely to choose psychiatry as a career., Conclusion: More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students' interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students' attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.

Background: Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development., Methods: Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique., Results: We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation., Conclusion: In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.

Objective: Synovial inflammation plays an important role in the pathogenesis of osteoarthritis (OA), and β4GalT1 has been reported to be involved in the inflammatory process. The aim of our study was to investigate the role of β4GalT1 in the progression of inflammation and analyze the association between β4GalT1 and tumor necrosis factor (TNF)-α in human OA fibroblast-like synoviocytes (FLS)., Patients and Methods: Primary cultured FLS isolated from OA synovial tissues were cultured, and the levels of β4GalT1, TNF-α, MMP-3, p/t-ERK, p/t-JNK, and p/t-P38 were analyzed by Western blotting. An enzyme-linked immunosorbent assay (ELISA) was performed to measure the secretion of TNF-α, interleukin (IL)-1β, and IL-6 in OA-FLS. Immunofluorescence staining was used to examine the co-localization of β4GalT1 and TNF-α or THY1. RT-PCR was used to detect the transfection efficiency of β4GalT1., Results: The expression of β4GalT1 was increased in OA-FLS. β4GalT1 promoted cell invasion, MMP-3 production, and the secretion of TNF-α, IL-1β, and IL-6. si-TNF-α attenuated the β4GalT1-enhanced cell invasion and inflammatory factor secretion in OA-FLS. Furthermore, β4GalT1 increased autocrine TNF-α signaling in OA-FLS. β4GalT1 knockdown successfully decreased autocrine TNF-α activity, while β4GalT1 overexpression increased autocrine TNF-α activity in OA-FLS. Moreover, β4GalT1 enhanced the ERK, JNK, and P38 MAPK signaling pathways through the induction of autocrine TNF-α signaling in OA-FLS., Conclusions: β4GalT1 may promote the inflammatory progression of OA-FLS by enhancing autocrine TNF-α signaling.

Background: The pathophysiology of cognitive impairment in patients with the major depressive disorder (MDD) may involve neuroinflammation mediated by cytokines., Objective: The aim of this study was to examine the serum interleukin-6 (IL-6) levels, sustained attention, and their association in patients with MDD., Methods: Thirty patients with MDD and 30 healthy controls were enrolled in this case-control study. Sustained attention was measured using the Rapid Visual Information Processing (RVP) task in the Cambridge Neuropsychological Tests Automated Battery. The serum IL-6 levels of all subjects were assessed by sandwich enzyme-linked immunosorbent assays., Results: There were significant differences in the log10RVP total hits, log10RVP total misses, and log10RVP mean latency between patients with MDD and healthy controls (F = 6.04, p = 0.017; F = 19.77, p < 0.0001; F = 14.42, p < 0.0001, respectively). The serum levels of Log10IL-6 were significantly higher in patients with MDD than in healthy controls (F = 192.27, p < 0.0001). The log10IL-6 levels were also positively correlated with the log10RVP mean latency in patients with MDD (r = 0.45, p = 0.013). A further stepwise multivariate regression analysis indicated that the log10IL-6 levels were significantly associated with the log10RVP mean latency in patients with MDD (β = 0.31, t = 2.41, p = 0.025)., Conclusions: Our data suggested that increased IL-6 levels were associated with the psychopathology of MDD, and that abnormal IL-6 levels were implicated in the impairment of sustained attention in patients with MDD.

Objective: To investigate the diagnostic value of Hepcidin as a sepsis biomarker in critically ill adults., Methods: An observational study was conducted. The patients with suspected or proven infection admitted to intensive care unit (ICU) of Zhoupu Hospital Affiliated to Shanghai University of Medicine and Health Sciences from March 2016 to November 2017 were enrolled. According to the third international consensus definitions for sepsis and septic shock (Sepsis-3), the patients were divided into non-sepsis group and sepsis group, and the septic patients were subdivided into general sepsis subgroup and septic shock subgroup according to the severity of disease. The differences in serum Hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC), neutrophil granulocytes (NEUT) and lactic acid (Lac) within 1 hour after ICU admission between non-sepsis and sepsis groups and among the sepsis subgroups were compared. The acute physiology and chronic health evaluation II (APACHE II) within 24 hours after ICU admission and sequential organ failure score (SOFA) were recorded, and the mortality rate was followed up for 28 days. Receiver operation characteristic curve (ROC) was used to evaluate and compare the diagnostic value of Hepcidin and PCT, CRP, WBC for sepsis. Logistic regression model was used to estimate the association between Hepcidin and sepsis. Spearman correlation analysis was used to analyze the correlation between Hepcidin and other parameters of sepsis patients., Results: A total of 183 patients were enrolled, 93 in the non-sepsis group and 90 in the sepsis group (48 with general sepsis and 42 with septic shock). (1) The levels of Hepcidin, IL-6, TNF-α, PCT, Lac in serum, and APACHE II and SOFA scores in the sepsis group were significantly higher than those in the non-sepsis group. ROC analysis showed that the area under the ROC curve (AUC) of Hepcidin and PCT for sepsis diagnosis were 0.865 [95% confidence interval (95%CI) = 0.807-0.911] and 0.848 (95%CI = 0.788-0.897), respectively, without statistical significance (Z = 0.443, P = 0.657). Furthermore, the AUC of Hepcidin for sepsis diagnosis was significantly higher than that of the conventional biomarkers CRP and WBC [AUC was 0.530 (95%CI = 0.455-0.604) and 0.527 (95%CI = 0.452-0.601), respectively] with statistical significance (both P < 0.01). When Hepcidin > 54.00 μg/L, its sensitivity for sepsis diagnosis was 95.56%, specificity was 66.67%, positive and negative predictive value was 73.51% and 93.94%, respectively. Parallel test was conducted for combination of Hepcidin and PCT, which showed that the AUC was 0.885, and the sensitivity and negative predictive value was significantly improved to 98.96% and 98.36%, respectively. Logistic regression analysis demonstrated that after adjusted for PCT, Hepcidin > 54.00 μg/L was also associated with sepsis independently, with odds ratio (OR) of 1.011 (95%CI = 1.008-1.015, P < 0.001), indicating that Hepcidin and PCT were not completely overlapped in the diagnosis of sepsis. (2) With the increase in infection severity, serum Hepcidin, PCT, IL-6, TNF-α, Lac, APACHE II, SOFA score and 28-day mortality all showed an increasing trend in patients. There was a significantly positive correlation between Hepcidin and IL-6, TNF-α, PCT, APACHE II, and SOFA in the sepsis patients (r value was 0.526, 0.449, 0.591, 0.359, and 0.374, respectively, all P < 0.01), but no correlation was found between Hepcidin and Lac (r = 1.104, P > 0.05)., Conclusions: Serum Hepcidin is a useful biomarker for the diagnosis of sepsis, and it is correlated to the severity of the sepsis. The combination of Hepcidin and PCT can improve the accuracy of diagnosis of sepsis., Clinical Trial Registration: China Clinical Trial Registration Center, ChiCTR-DDD-16008522.

Background: Elevated phospholipase A2 (PLA2) activity is reported to be involved in the development of schizophrenia. Further study revealed an association between PLA2 groups XIIA (PLA2G12A) polymorphism and patients with schizophrenia in a northeast Chinese Han population., Objective: This study will further examine whether PLA2G12A rs3087494 polymorphism is associated with patients with schizophrenia in a southern Chinese Han population., Methods: This polymorphism was genotyped in 438 patients with schizophrenia (diagnosed according to Diagnostic and Statistical Manual of Mental Disorders-IV) and 876 healthy controls using a case-control design. Demographic and clinical data were collected in all subjects., Results: The allele and genotype frequencies of PLA2G12A rs3087494 polymorphism significantly differed between groups (both, p < .001). These differences still were significant by adjusting for sex and age. However, there was no difference in age at onset among 3 genotype groups in patients with schizophrenia by adjusting for the variables (F = 0.22, p = .80). Stepwise multivariate regression analysis showed that this polymorphism was not associated with age at onset in patients with schizophrenia (β = .008, t = .07, p = .94)., Conclusions: Our results indicated that even though PLA2G12A rs3087494 polymorphism did not influence age at onset in patients with schizophrenia, it may play an important role in the susceptibility to schizophrenia in a southern Chinese Han population., (Copyright © 2018 John Wiley & Sons, Ltd.)

Objectives: It is not clear whether TREM-2 (the "triggering receptor expressed on myeloid cells 2") is expressed in fibroblast-like synovial cells (FLSs). In this study, we aimed to determine the expression of TREM-2 in rheumatoid arthritis (RA)-FLSs and explore whether and how TREM-2 modulates the function of RA-FLSs., Methods: Western blot and RT-PCR were used to detect the expression of TREM-2 in RA-FLSs, siRNA and lentivirus were used to down-regulate and up-regulate the expression of TREM-2 in RA-FLSs. Then mRNA expression of IL-1β, IL-6, and MMP-13 was determined by RT-qPCR. Protein secretion of IL-1β, IL-6, and MMP-13 in the supernatant was determined by ELISA assay; expression of cell signal transduction molecules was determined by western blot., Results: A: Relative to OA-FLSs, mRNA and protein expression levels of TREM-2 in RA-FLSs are significantly elevated. TREM-2 protein is mainly expressed in the cytoplasm of RA-FLSs; B: In RA, the expression of TREM-2 was reduced at first and then up-regulated after stimulation by TNF-α. TREM-2 also inhibited the activation of TNF-α induced of inflammation in RA-FLSs by the p38 pathway, which regulates the production of cytokines and matrix metalloproteinases., Conclusions: TREM-2 expressed in RA-FLSs and TNF-α mediated reduction of inflammatory reactions. These phenomena indicated that TREM-2 may be a potential target in the treatment of RA.

Rheumatoid arthritis (RA) is an immune-mediated disease that causes chronic inflammation of the joints and involves CD4+ T cell activation. In RA, CD4+ T cells are the main drivers of disease initiation and the perpetuation of the damaging inflammatory process. In the present study, we investigated the role of Lysine-specific histone demethylase 1 (LSD1) in RA. The frequency of LSD1-positive CD4+ T cells in the synovial fluid (SF) of active RA patients was higher than that of inactive RA patients. In CD4+ T cells isolated from SF of active RA patients, LSD1 downregulation significantly increased cell proliferation, as shown by MTT assay. LSD1 knockdown also significantly increased the production of IFN-γ and IL-17, and increased that of IL-10, as determined by ELISA and qRT-PCR aasay. In CD4+ T cells isolated from SF of inactive RA patients, LSD1 was overexpressed by LSD1 plasmid transfection. As expected, LSD1 overexpression resulted in an opposite effect on cell proliferation and the production of cytokines, including IFN-γ, IL-17 and IL-10. LSD1 was downregulated in RA mouse by lenti-vector infection. As expected, LSD1 knockdown in vivo significantly alleviated the disease severity and increased the levels of anti-collagen II antibodies. LSD1 downregulation in the early stage was more effective to ameliorate disease severity. Our data suggested the potential therapeutic role of LSD1 in RA patients., Competing Interests: None., (IJCEP Copyright © 2018.)

Background/aims: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process., Materials: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay., Results: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg2+/ Mn2+-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts., Conclusion: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

A novel prognostic nomogram predicting post-transplant pulmonary metastasis was established with a primary cohort of 308 HCC patients who received liver transplantation between 2007 and 2011 at Ren Ji Hospital. The C-indexes for predicting pulmonary metastasis was 0.85. The calibration curves fitted well between the predicted and actual outcomes. The decision curve analysis indicated that our nomogram was the optimal decision-making strategy for PM prediction compared to Milan, University of California San Franscisco, and up-to-seven criteria. These results were further validated by data from 103 patients who underwent liver transplantation between 2011 and 2012 at the same institution. In conclusion, our nomogram could be used as an effective tool to predict PM after liver transplantation., Competing Interests: CONFLICTS OF INTEREST The authors declared that they have no conflicts of interest in this work.

Background: LncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) is reportedly dysregulated in various cancers. We performed this meta-analysis to clarify the efficacy of PANDAR as a prognostic marker in malignant tumors., Methods: The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to July 3, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between PANDAR expression and overall survival (OS). Odds ratios (ORs) were calculated to assess the association between PANDAR expression and pathological parameters., Results: Eight original studies covering 1,132 cancer patients were included. The pooled HR suggested that high PANDAR expression correlated with poor OS (pooled HR=1.60, 95% CI: 1.09-2.33) in cancer patients. PANDAR expression was also related to lymph node metastasis (OR=3.26, 95% CI: 2.09-5.09), advanced tumor stage (OR=3.60, 95% CI: 2.39-5.44) and histological grade (OR=2.75, 95% CI: 1.73-4.38). Begg's funnel plot showed no evidence of obvious asymmetry for overall survival and lymph node metastasis., Conclusions: Thus high PANDAR expression appears predictive of poor OS, lymph node metastasis, advanced tumor stage and histological grade in multiple cancers. This suggests PANDAR expression could serve as a biomarker of poor prognosis in Chinese cancer patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In this study, we report a simple and efficient two-step method consisting of water-in-oil (W/O) emulsion technique and subsequent annealing process for synthesizing the hollow reduced graphene oxide microspheres embedded with Co nanoparticles (Air@rGO€Co). The microspheres showed good electromagnetic properties because of the coexistence of magnetic loss and dielectric loss to microwaves. The minimum reflection loss (RL min ) value of S 1.5 reaches -68.1 dB at 13.8 GHz with a thickness of 2.2 mm, and the absorption bandwidth (lower than -10 dB) is 7.1 GHz covering from 10.9 GHz to 18.0 GHz. More interestingly, we can easily controll the microwave absorbing properties of the microspheres by changing the ratio of the two components in the composites. The excellent electromagnetic match at the corresponding resonance peaks for dielectric and magnetic loss play an important role in improving microwave absorption property. Our study provides a good potential method for preparation of lightweight microwave absorbing materials.

Background: Cognitive deficits have been identified as one of core clinical symptoms of major depressive disorder (MDD). Accumulating evidence indicated that triglycerides (TG) might be associated with MDD and cognitive decline., Objective: This study examined whether patients with MDD had poorer cognitive functions than healthy controls, and further investigate whether TG levels were involved in MDD, and its cognitive impairments in a Han Chinese population., Method: 115 patients with MDD and 119 healthy controls were enrolled. Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum TG levels were examined using enzymatic colorimetry., Results: TG levels were higher in patients with MDD than healthy controls after controlling for the variables. Cognitive test scores were lower in patients with MDD than healthy controls except for visuospatial/constructional index after controlling for the variables. TG levels were negatively correlated with visuospatial/constructional score, delayed memory score and RBANS total score of MDD. Further multivariate regression analysis showed that TG levels were negatively associated with visuospatial/constructional score, attention score, delayed memory score and RBANS total score of MDD., Conclusions: Our findings supported that serum TG levels might be involved in MDD, and play an important role in cognitive impairments of MDD, especially in delayed memory. Moreover, patients with MDD experienced greater cognitive impairments than healthy controls except for visuospatial/constructional index., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Hard carbons attract myriad interest as anode materials for high-energy rechargeable batteries due to their low costs and high theoretical capacities; practically, they deliver unsatisfactory performance due to their intrinsically disordered microarchitecture. Here we report a facile ion-catalyzed synthesis of a phenol-formaldehyde resin-based hard-carbon aerogel that takes advantage of the chelation effect of phenol and Fe 3+ , which consists of a three-dimensionally interconnected carbon network embedded with hydrogen-rich, ordered microstructures of expanded nanographites and carbon micropores. The chelation effect ensures the homodispersion of Fe in the polymer segments of the precursor, so that an effective catalytic conversion from sp 3 to sp 2 carbon occurs, enabling free rearrangement of graphene sheets into expanded nanographite and carbon micropores. The structural merits of the carbon offer chances to achieve lithium/sodium storage performance far beyond that possible with the conventional carbon anode materials, including graphite and mesocarbon microbeads, along with fast kinetics and long cycle life. In this way, our hard carbon proves its feasibility to serve as an advanced anode material for high-energy rechargeable Li/Na batteries.

Traumatic spinal cord injury (SCI) causes tissue loss and associated neurological dysfunction attributable to both mechanical damage and secondary biochemical and physiological responses. Upregulation of cell cycle proteins occurs in both neurons and glia after SCI and may contribute to these changes. Increased cell cycle protein is associated with neuronal and oligodendroglial apoptosis, reactive astrogliosis, glial scar formation, and microglial activation. Here, using lentiviral vectors (LV), we induced the expression of the cyclin-dependent kinase (CDK) inhibitor p27 kip1 in the lesioned spinal cord of adult rat. Treatment with LV-p27 kip1 significantly reduced the expression of cell cycle proteins and improved functional recovery. In addition, p27 kip1 overexpression also reduced lesion volume, decreased astrocytic reactivity, attenuated microglial activation, reduced cell death, and improved the local microenvironment. We suggest that these effects reflect the ability of p27 kip1 to inhibit cell cycle pathways. Thus, the present study provides further support for the therapeutic potential of cell cycle inhibitors in the treatment of SCI.

Self-assembly has a unique presence when it comes to creating complicated, ordered supramolecular architectures from simple components under mild conditions. Here, we describe a self-assembly strategy for the generation of the first homogeneous supramolecular metal-organic framework (SMOF-1) in water at room temperature from a hexaarmed [Ru(bpy)3](2+)-based precursor and cucurbit[8]uril (CB[8]). The solution-phase periodicity of this cubic transition metal-cored supramolecular organic framework (MSOF) is confirmed by small-angle X-ray scattering and diffraction experiments, which, as supported by TEM imaging, is commensurate with the periodicity in the solid state. We further demonstrate that SMOF-1 adsorbs anionic Wells-Dawson-type polyoxometalates (WD-POMs) in a one-cage-one-guest manner to give WD-POM@SMOF-1 hybrid assemblies. Upon visible-light (500 nm) irradiation, such hybrids enable fast multi-electron injection from photosensitive [Ru(bpy)3](2+) units to redox-active WD-POM units, leading to efficient hydrogen production in aqueous media and in organic media. The demonstrated strategy opens the door for the development of new classes of liquid-phase and solid-phase ordered porous materials.

Liver transplantation (LT) has been accepted as an effective therapy for hepatocellular carcinoma (HCC). The Milan criteria (MC) are widely used across the world to select LT candidates in HCC patients. However, the MC may be too strict because a substantial subset of patients who have HCC exceed the MC and who would benefit from LT may be unnecessarily excluded from the waiting list. In recent years, many extended criteria beyond the MC were raised, which were proved to be able to yield similar outcomes compared with those patients meeting the MC. Because the simple use of tumor size and number was insufficient to indicate HCC biological features and to predict the risk of tumor recurrence, some biological markers such as Alpha-fetoprotein, Des-Gamma-carboxy prothrombin and the neutrophil-to-lymphocyte ratio were useful in selecting LT candidates in HCC patients beyond the MC. For patients with advanced HCC, downstaging therapy is an effective way to reduce the tumor stage to fulfill the MC by using liver-directed therapy such as transarterial chemoembolization, radiofrequency ablation and percutaneous ethanol injection. This article reviews the recent advances in LT for HCC beyond the MC.

Anabolic bone accruement through osteogenic differentiation is important for the maintenance of physiological bone mass and often disrupted in various inflammatory diseases. Epigallocatechin-3-gallate, as an antioxidant and anti-inflammatory agent, has been suggested for potential therapeutic use in this context, possibly by the inhibition of bone resorption as well as the enhancement of bone formation through directly activating osteoblast differentiation. However, the reported effects of epigallocatechin-3-gallate modulating osteoblast differentiation are mixed, and the underlying molecular mechanism is still elusive. Moreover, there is limited information regarding the effects of epigallocatechin-3-gallate on osteogenic potential of mesenchymal stem cell in inflammation. Here, we examined the in vitro osteogenic differentiation of human mesenchymal stem cells. We found that the cell viability and osteoblast differentiation of human bone marrow-derived mesenchymal stem cells are significantly inhibited by inflammatory cytokine TNFα treatment. Epigallocatechin-3-gallate is able to enhance the cell viability and osteoblast differentiation of mesenchymal stem cells and is capable of reversing the TNFα-induced inhibition. Notably, only low doses of epigallocatechin-3-gallate have such benefits, which potentially act through the inhibition of NF-κB signaling that is stimulated by TNFα. These data altogether clarify the controversy on epigallocatechin-3-gallate promoting osteoblast differentiation and further provide molecular basis for the putative clinical use of epigallocatechin-3-gallate in stem cell-based bone regeneration for inflammatory bone loss diseases, such as rheumatoid arthritis and prosthetic osteolysis., (© 2016 by the Society for Experimental Biology and Medicine.)

Aim: The third ventricle is located deep in the brain and is adjacent to important neurovascular structures. This makes tumor resection in this region difficult and causes more postoperative complications than surgeries in other regions of the brain. The objective of this study was to investigate the feasibility and clinical effects of transcallosal-interforniceal approach for microsurgical removal of the third ventricle tumors., Methods: After preoperative evaluation, 23 patients with the third ventricle tumors were microsurgically operated using the transcallosal-interforniceal approach., Results: Of these 23 patients, 12 (52.2%) underwent total excision, 9 (39.1%) had subtotal resection, and the remaining 2 (8.7%) underwent partial excision. After surgery, the following complications were observed: diabetes insipidus (11 patients), hemorrhages of the upper digestive tract (2 patients), central fever (1 patient), and memory impairment (1 patient). No mortality in the perioperative period was reported., Conclusion: The surgical procedure using the transcallosal-interforniceal approach is direct and provides good surgical field exposure and fewer post operational compilations. This approach should be considered as the method of choice for surgical removal of the third ventricle tumors.

Living-donor liver transplantation (LDLT) has increasingly performed all around the world. However, LDLT donors achieve no medical benefits and are exposed to the risk of complications, and even death. The potential effects of LDLT on donor safety, donor recovery, and post-donation psychological impairment are essential to be better understood. We searched the MEDLINE database to identify articles about the quality of life (QOL) in adults after LDLT donation. Twenty-eight studies with a total of 1944 donors were included in the review. 14 of the 28 studies (50%) had a cross-sectional design, and the remaining half had a prospective design. The Physical Component Score (PCS) decreased immediately after the donation, then returned to the baseline within 6 to 12 months while the Mental Component Score (MCS) remains comparable to that of normative population throughout the procedure. Compared with the left graft (LG) donors, right graft (RG) donors were significantly older, had longer hospital stays and higher rates of postoperative complications, and a higher recipient mortality rate, while there were no difference in the PCS and MCS between the two groups. Our review clearly indicates that the LDLT donors can endure the donation procedure and return to their normal daily life without major problem in the short term. However, to improve the donor selection criteria and ensure the QOL in donors throughout donation procedure, more studies with longer follow up and larger samples are essential and predictors of poor QOL should be identified in study with sufficient response rate and ideal control groups.