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Halide-free deep eutectic solvents (DESs) derived from natural biological compounds were used to gently catalyze the cycloaddition reaction between CO 2 and epoxides, with a TOF of 645 h -1 . The DFT calculation result was in good agreement with the experiment result, indicating that the ring closure process was the rate-determining step.

Background: Behavioral and emotional problems are common and often co-occur during childhood and adolescence. The aim of this study was to assess gender differences in the network structures of behavioral and emotional problems of children and adolescents in China based on a national survey., Methods: The Parent version of Achenbach' s Child Behavior Checklist (CBCL) was used to assess behavioral and emotional problems. To account for potential confounding factors in comparisons between boys and girls, propensity score matching was utilized. Network model differences were assessed using Network Comparison Test (NCT)., Results: Data from 60,715 children and adolescents were included for analyses. Boys exhibited more severe total behavioral and emotional problems compared to girls. While several edges showed significant differences between boys and girls, the strongest association was consistently found between "Attention problems" (CBCL6) and "Aggressive behavior"(CBCL8) in both boys and girls, regardless of age. Network centrality was higher among adolescents compared to children. The most central problems commonly found across different genders and age groups were "Aggressive behavior" (CBCL8) (centrality values were 1.142 for boys aged 6-11 years, 1.051 for boys aged 12-16 years, 1.148 for girls aged 6-11 years, and 1.028 for girls aged 12-16 years), "Anxious/depressed" (CBCL1) (centrality values of 0.892 for boys aged between 6 and 11 years, 1.031 for boys aged 12-16 years, 0.951 for girls aged 6-11 years, and 1.099 for girls aged 12-16 years) and "Social problems" (CBCL4) (centrality values of 1.080 for boys aged 6-11 years, 0.978 for boys aged 12-16 years, 1.086 for girls aged between 6 and 11 years, and 0.929 for girls aged 12-16 years)., Conclusion: Testing effective interventions that address aggressive behavior, anxiety/depression, and social problems may be beneficial for reducing risk of psychopathology among children and adolescents., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest None declared.

Objectives: Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the key metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress., Methods: ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient-derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo., Results: We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models., Discussion: our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2.

Background: Asfotase alfa (AA) is an FDA-approved enzyme replacement therapy for hypophosphatasia (HPP). Limited real-world data on its adverse events (AEs) exist. This study evaluates AA-related AEs using the U.S. FDA's Adverse Event Reporting System (FAERS) database., Methods: Reports for AA were extracted from FAERS and analyzed per FDA guidelines. AEs were categorized using MedDRA version 26.1. Disproportionality analysis was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM) algorithms. Time-to-onset (TTO) was calculated, with a Weibull shape parameter test to assess risk over time., Results: Out of 13,702,373 reports, 5,040 AA-related AEs were identified, with 198 significant preferred terms (PTs). Common AEs included injection site reactions and pain, with additional PTs for ear/labyrinth disorders and infections. The median onset for 234 AEs with reported times was 170 days (IQR 18-390 days). No significant differences in AEs were found across gender or age groups., Conclusion: Most AEs align with known data, but newly identified ear/labyrinth disorders and infections require further investigation to enhance AA's safety profile.

The influence of China's "one-child" policy on the mental health of children and adolescents is still unclear. This study examined the associations between number of children and children's mental health using data from the national school children and adolescents survey of China. Mental health was measured using the Achenbach's Child Behavior Checklist (CBCL). Linear regression models were used to explore the relationship between number of children per family and children's mental health. A total of 64,017 students were enrolled, with 68.60 % from one-child families. Compared with children from one-child families, those from multiple-children families had significantly higher scores on the total CBLC and each of its subscales (all P<0.001). Analyses suggested children from multiple-child families have a higher risk of mental health problems (total problems on the CBCL: adjusted B=2.217, 95 %CI=1.883-2.550, P<0.001). Regular mental health assessments should be implemented and effective interventions should be developed for those in need., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Exploring networks of mental and behavioral problems in children and adolescents may identify differences between one-child and multi-child families. This study compared the network structures of mental and behavioral problems in children and adolescents in one-child families versus multi-child families based on a nationwide survey., Methods: Propensity score matching (PSM) was used to match children and adolescents from one-child families with those from multi-child families. Mental and behavioral problems were assessed using the Achenbach's Child Behavior Checklist (CBCL) with eight syndromal subscales. In the network analysis, strength centrality index was used to estimate central symptoms, and case-dropping bootstrap method was used to assess network stability., Results: The study included 39,648 children and adolescents (19,824 from one-child families and 19,824 from multi-child families). Children and adolescents from multi-child families exhibited different network structure and higher global strength compared to those from one-child families. In one-child families, the most central symptoms were "Social problems", "Anxious/depressed" and "Withdrawn/depressed", while in multi-child families, the most central symptoms were "Social problems", "Rule-breaking behavior" and "Anxious/depressed"., Conclusion: Differences in mental and behavioral problems among children and adolescents between one-child and multi-child families were found. To address these problems, interventions targeting "Social problems" and "Anxious/depressed" symptoms should be developed for children and adolescents in both one-child and multi-child families, while other interventions targeting "Withdrawn/depressed" and "Rule-breaking behavior" symptoms could be useful for those in one-child and multi-child families, respectively., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Myocarditis is an important clinical issue which lacks specific treatment by now. Ivermectin (IVM) is an inhibitor of importin α/β-mediated nuclear translocation. This study aimed to explore the therapeutic effects of IVM on acute myocarditis., Methods: Mouse models of coxsackie B3 virus (CVB3) infection-induced myocarditis and experimental autoimmune myocarditis (EAM) were established to evaluate the effects of IVM. Cardiac functions were evaluated by echocardiography and Millar catheter. Cardiac inflammatory infiltration was assessed by histological staining. Cytometric bead array and quantitative real-time PCR were used to detect the levels of pro-inflammatory cytokines. The macrophages and their M1/M2 polarization were analyzed via flow cytometry. Protein expression and binding were detected by co-immunoprecipitation, Western blotting and histological staining. The underlying mechanism was verified in vitro using CVB3-infected RAW264.7 macrophages. Cyclic polypeptide (cTN50) was synthesized to selectively inhibit the nuclear translocation of NF-κB/p65, and CVB3-infected RAW264.7 cells were treated with cTN50., Results: Increased expression of importin β was observed in both models. IVM treatment improved cardiac functions and reduced the cardiac inflammation associated with CVB3-myocarditis and EAM. Furthermore, the pro-inflammatory cytokine (IL-1β/IL-6/TNF-α) levels were downregulated via the inhibition of the nuclear translocation of NF-κB/p65 in macrophages. IVM and cTN50 treatment also inhibited the nuclear translocation of NF-κB/p65 and downregulated the expression of pro-inflammatory cytokines in RAW264.7 macrophages., Conclusions: Ivermectin inhibits the nuclear translocation of NF-κB/p65 and the expression of major pro-inflammatory cytokines in myocarditis. The therapeutic effects of IVM on viral and non-viral myocarditis models suggest its potential application in the treatment of acute myocarditis., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB)., Methods: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists., Results: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists., Conclusion: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: To understand research advances and frontiers of acupuncture regulation on the autonomic nervous system (ANS) over the past decade through a bibliometric analysis., Methods: Publications related to acupuncture regulation on the ANS were retrieved from the Web of Science Core Collection (WoSCC) database. CiteSpace software was used to analyze the datasets and generate knowledge maps., Results: A total of 445 relevant publications published between 2013 and 2022 were included in this bibliometric analysis. The number of annual publications fluctuated from 2013 to 2016 but increased gradually from 2016 to 2022. China produced the highest number of publications, while the USA established the most extensive cooperation relationships. China Academy of Chinese Medical Science was the most productive institution. Chen Jiande D.Z. was the most prolific author and Rong Peijing holds the most extensive cooperation network. Han Jisheng was the most co-cited author. Relevant research involved mechanism exploration and clinical efficacy research, and "anti-inflammatory effect" was the most active research topic, especially cholinergic anti-inflammatory mechanisms. The most cited references mainly focused on inflammation. Gastrointestinal and cardiovascular disorders were the most active medical conditions studied in this field., Conclusions: Research related to acupuncture regulation on the ANS mainly focused on anti-inflammation, and regulating gastrointestinal and cardiovascular function over the past decade. However, the mechanisms of the autonomic effects of acupuncture need further investigation. High-quality clinical studies are required to determine the optimal parameters of acupuncture for clinical application., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product,service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background . Characteristics of X-linked Alport syndrome (XLAS) in a cohort of Chinese children. Methods . This work is a retrospective study covering the clinical information, pathological data, and gene sequencing results of 32 cases with XLAS from 2011 to 2022. Results . Among these 32 patients, the youngest age of onset was 3 months. Renal biopsy was performed on 29 children. The lamellated glomerular basement membrane was observed in 19 children using electron microscopy (65.5%). Of the 26 samples tested, 73.1% were found to be negative for collagen-a5 under immunohistochemical staining, showing clinical significance. Next-generation sequencing (NGS) detected 27 pathogenic gene mutations. A total of 15.4% of patients carried de novo mutations. Conclusions . The boys with XLAS showed more typical pathological performance than the girls. Patients with severe mutation were more likely to have proteinuria and hearing impairment. Renal pathology combined with NSG is an important means of diagnosis of AS., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Ionic liquids (ILs) are generally considered eco-friendly alternatives to conventional industrial solvents, but they are hard to degrade and easily accumulate in the environment. Therefore, their long-term toxicities are especially vital to estimate their potential risk. However, the chronic toxicities of ILs over generations lacked intensive investigation. In the present work, acute toxicity and chronic toxicity of 1-methyl-3-octylimidazolium chloride ([Omim]Cl) and 1-dodecylpyridinium chloride ([DPy]Cl) were studied on Moina macrocopa with the first exposed generation (F0) and two successive recovery generation (F1 to F2). The acute results showed that both [Omim]Cl and [DPy]Cl exhibited high toxicity to M. macrocopa. The chronic results indicated that the exposure of [Omim]Cl and [DPy]Cl could inhibit the survivorship, body length, and reproduction of M. macrocopa and exhibited a significant dose-related decrease. Furthermore, these two types of ILs presented intergenerational toxicity in the water flea. And the toxic effects of [Omim]Cl disappeared in the recovery tests of F2 generation, while the [DPy]Cl toxic effects continued. Our research suggested a potential risk for the aquatic ecosystem induced by ILs. And the damage done by these chemicals to the aquatic environment is worthy of attention., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Artesunate, a derivative of artemisinin, has anti-malarial effects, and in recent years has also been reported to have anti-tumor activity. However, its anti-tumor mechanisms are not well understood. Methods: In this study, we focused on the targeting of Hsp90 by artesunate to inhibit tumor cell proliferation, which we examined using immunoprecipitation, a proliferation assay, flow cytometry, western blotting, a tumor xenograft animal model, and immunohistochemistry. Furthermore, to examine the tumor-suppressive effects of artesunatein nude mice, we used artesunate-loaded PLGA-PEG nanoparticles. Results: The binding of artesunate to Hsp90 was found to reduce the expression of its client proteins AKT, ERK, p-AKT, p-ERK, and EGFR, thereby blocking the cell cycle at the G0/G1 → S stage in lymphoma cells and inducing apoptosis. In addition, the results of tumor xenograft experiments revealed that artesunate reduced the expression of AKT and ERK proteins in tumor tissues, inhibited tumor proliferation, and reduced tumor size and weight. Furthermore, nanoparticle encapsulation was demonstrated to enhance the anti-cancer activity of artesunate. Discussion: We thus established that artesunate inhibits the proliferation of lymphoma cells by targeting the Hsp90 protein, and we accordingly believe that this compound has potential for development as a novelanti-tumor drug., 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 Yuan-Ce, Qi, Hong-Yang, Yan-Wen, Yu-Mei, Bi-Juan and Jun-Lin.)

With the increasing use and production of "green solvents" ionic liquids (ILs) and their known stability in the environment, the potential adverse effects of ILs have become a focus of research. In the present study, acute, chronic, and intergenerational toxic effects of an imidazolium-based ionic liquid, 1-decyl-3-methylimidazolium hexafluorophosphate ([Demim]PF 6 ), on Moina macrocopa were investigated following the parental exposure. The results showed that [Demim]PF 6 exhibited high toxicity to M. macrocopa, and the long-term exposure significantly inhibited the survivorship, development, and reproduction of the water flea. Furthermore, it is also observed that [Demim]PF 6 induced toxic effects in the following generation of M. macrocopa, resulting in the complete cessation of reproduction in the first offspring generation, and the growth of the organisms was also significantly affected. These findings provided a novel insight into the intergenerational toxicity induced by ILs to crustaceans and suggested that these compounds pose potential risks to the aquatic ecosystem., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Physalis pubescens L. is an annual or perennial plant in the family Solanaceae It is used in traditional medicine for treating sore throats, coughs, urinary discomfort, and astringent pain, and externally for pemphigus and eczema in northern China. The proliferation inhibitory activity and mechanisms of the ethyl acetate extract (PHY-EA) from the leaves of Physalis pubescens were investigated. High performance liquid chromatography was used to identify the chemical composition of PHY-EA; sulforhodamine B was used to detect the proliferation inhibitory effect of PHY-EA on MCF-7, CA-46, Hela, HepG2, B16, and other tumor cells; flow cytometry was used to detect the effect of PHY-EA on the lymphoma cell cycle and apoptosis; Western blot was used to detect the expression of the cycle- and apoptosis-related proteins. The expression of Ki-67 and cleaved caspase 3 was detected by immunohistochemistry. The results showed that PHY-EA contained physalin B, physalin O, and physalin L. PHY-EA blocked the cell cycle of G2/M→G0/G1 in lymphoma cells and induced apoptosis in tumor cells. Mouse transplantation tumor experiments showed that PHY-EA had a significant inhibitory effect on mouse transplantation tumors, and the tumor volume and weight were significantly reduced. In conclusion, PHY-EA has a good antiproliferative effect on Burkkit lymphoma, indicating its potential medicinal value., 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 Yuan-Ce, Yu-Yan, Qi, Hong-Yang, Yan-Wen, Yu-Mei, Guang-Zhi and Jun-Lin.)

Juvenile hormone analogues (JHAs) are a kind of effective insecticide. These compounds have relatively low toxicity for fish, birds, and mammals, so they are increasingly used in insect pest control. However, JHAs may cause various adverse effects in crustaceans as in insects, because they have a close evolutionary relationship and possess similar juvenile hormone systems. To date, the chronic toxicities of JHAs over generations lacked intensive investigation. The present study evaluated the acute, chronic, and transgenerational effects of a terpenoid JHA, kinoprene, using the water flea Moina macrocopa. The result of acute exposure shows that kinoprene exhibited high toxicity to M. macrocopa. The chronic results indicate that kinoprene inhibited the survivorship, development, and reproduction of the organism. Moreover, the adverse effects induced by kinoprene continued in the F2 generation with no direct exposure but recovered in the F3 generation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: The prognostic implication of left ventricular (LV) torsion on ST-elevation myocardial infarction (STEMI) is unclear., Methods and Results: We analysed cardiovascular magnetic resonance (CMR) findings of 420 patients from a registry study (NCT03768453). These patients received CMR examination within 1 week after timely primary percutaneous coronary intervention. LV torsion and other CMR indexes were measured. Compared with healthy control subjects, STEMI significantly decreased patients' LV torsion (1.04 vs. 1.63°/cm, P < 0.001). During follow-up (median, 52 months), the reduction of LV torsion was greater in patients with than without composite major adverse cardiac and cerebrovascular events (MACCEs, 0.79 vs. 1.08°/cm, P < 0.001). The risk of MACCEs would increase to 1.125- or 1.092-fold, and the risk of 1-year LV remodelling would increase to 1.110- or 1.082-fold for every 0.1°/cm reduction in LV torsion after adjustment for clinical or CMR parameters respectively. When divided dichotomously, patients with LV torsion≤ 0.802°/cm had significantly higher risk of MACCEs (40.2 vs. 12.3%, P < 0.001) and more remarkable LV remodelling (46.1 vs. 11.9%, P < 0.001) than patients with better LV torsion. The addition of LV torsion to conventional prognostic factors such as the LV ejection fraction and infarction size led to a better risk classification model of patients for both MACCEs and LV remodelling. Finally, tobacco use, worse post-PCI flow, and greater microvascular obstruction size were presumptive risk factors for reduced LV torsion., Conclusion: LV torsion measured by CMR is closely associated with the prognosis of STEMI and would be a promising indicator to improve patients' risk stratification., Clinical Trial Registration: Clinicaltrials.gov, NCT03768453., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The outbreak of COVID-19 disarranged lives across mainland China. No study has examined changes in psychological symptoms of healthcare professionals in the intensive care unit (ICU) before and after the outbreak of COVID-19. The aim of this study was to estimate changes in psychological symptoms of ICU healthcare professionals before and after the COVID-19 outbreak, and to analyze factors related to psychological symptoms., Methods: Two waves' administrations were implemented between December 13 and December 14, 2018, and between April 5 and April 7, 2020, respectively. The symptom checklist-90 (SCL-90) were used to evaluate psychological symptoms. Multiple logistical regression was used to reveal the risk of psychological symptoms., Results: A total of 3902 and 3908 ICU healthcare professionals took part in the first and second surveys. The mean total score of the SCL-90 was 179.27 (70.02) at wave 1 and 147.75 (58.40) at wave 2, respectively. The proportion of psychological symptoms was 55.6 % (95%CI = 54.0-57.1) at wave 1. But rates of psychological symptoms decreased to 36.6 % (95%CI = 35.1-38.2) at wave 2. ICU healthcare professionals with western economic belt and 6-10 years of work were more likely to develop psychological symptoms, while ICU healthcare professionals with the later survey and doctoral degree were less likely to develop psychological symptoms., Conclusion: Although COVID-19 period benefited psychological symptoms of ICU healthcare professionals, psychological symptoms still had a related high prevalence. Regular screening and appropriate interventions should still be implemented to decrease the risk for psychological symptoms among Chinese ICU healthcare professionals., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Topiramate (TPM) may reduce olanzapine (OLZ)-related weight gain and metabolism abnormalities in patients with schizophrenia. However, differences in the efficacy of OLZ-related weight gain and metabolism abnormalities between TPM and vitamin C (VC) are not clear. This study aimed to investigate whether TPM is more effective than VC in reducing OLZ-induced weight gain and metabolic abnormalities in patients with schizophrenia and explore their patterns., Methods: This was a 12-week longitudinal comparison study in OLZ-treated patients with schizophrenia. Twenty-two patients who received OLZ monotherapy plus VC treatment (OLZ + VC group) was matched to 22 patients who received OLZ monotherapy plus TPM treatment (OLZ + TPM group). Body mass index (BMI) and metabolism indicators were measured at baseline and 12-weeks follow-up., Results: A significant difference in triglyceride (TG) levels at different time points (pre-treatment: F = 7.89, p = 0.008; 4-weeks treatment: F = 13.19, p = 0.001; 12-weeks treatment: F = 54.48, p < 0.001) was found. Latent profile analysis demonstrated that a 2-class model for OLZ + TPM group (high vs. low BMI in the first 4 weeks) and OLZ + VC group (high vs. low), respectively., Conclusion: Our findings suggested that TPM could better mitigates OLZ-induced increase in TG levels. The trajectories of change also differed in all metabolic indexes over time between the two groups., 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 Zhang, Chen, Chen, Zhang and Rao.)

Objective: We aimed to explore a new method to reverse early relapse in patients with AML1-ETO-positive acute myeloid cell transplantation. Methods : A chidamide-based 3-drug combination regimen was used in our center to treat patients with AML1-ETO-positive AML post transplantation but negative flow cytometry results. A retrospective analysis was performed of the survival rate and possible influencing factors of patients with relapse treated with this regimen in our center from January 2018 to January 2022. Results : The overall response rate was 95.8% (23/24), and the median number of treatment courses was 4 (range, 3-12 courses). The total molecular complete response (MCR) was 79.1% (19/24) after all treatments, and the molecular complete response was 37.5% (9/24) after one cycle of treatment but reached 58.3% (14/24) after four cycles; overall, the proportion of MCR increased gradually with the increase in treatment cycles. The projected 5-year overall survival rate was 73.9%. The projected 5-year leukemia-free survival rate was 64.8%, and the projected 1-year cumulative relapse rate was 35.5%. The incidence of grade II-IV graft-versus-host diseases (GVHD) was 29.2% (7/24), and that of grade III-IV GVHD was 20.8% (5/24), which could be effectively controlled by glucocorticoid therapy combined with calcineurin inhibitors The total incidence of chronic GVHD was 29.2% (7/24), and all cases were localized chronic GVHD. The total infection rate was 33.3% (8/24), mainly involving bacterial and fungal infections, and the incidence of life-threatening infections was 4.17% (1/24). The treatment-related mortality rate was 0%; and the total mortality rate was 20.8% (5/24). Nausea and vomiting, thrombocytopenia, and neutropenia were common adverse reactions, all of which were Common Terminology Criteria for Adverse Events grade 2-3 events and reversible after drug withdrawal. In terms of immunity, Th1 cell counts gradually increased, Th17 cell counts gradually decreased, and the Th1/Th17 ratio gradually increased after treatment. The CD8 + T lymphocyte count increased gradually, while the CD4 + T lymphocyte count did not change significantly. Conclusion: Our chidamide-based 3-drug combination regimen led to a high remission rate and tolerable adverse reactions in patients with AML1-ETO-positive post-transplant relapse, and most patients can achieve long-term survival with this regimen., 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 Xi, Chenglong, Rong, Wen, Yu, Jiao, Juan, Feifei, Rong, Tao, Hui and Xiaobing.)

The main purpose of this work was to study a new method for evaluating the solidification of contaminated soil based on electrochemical impedance spectroscopy (EIS). To explore how the EIS parameters were affected by the pore structure and mesostructure of the cured system, the physical and mechanical properties, leaching toxicity, microstructure, and EIS of the stabilized contaminated soil were tested after 7, 28, 60, and 90 days of curing. Based on the EIS results, a physical and equivalent circuit model of the stabilized contaminated soil's impedance response was established to reveal the mechanism of binder-heavy metal ion-soil interaction. The results showed that as the red mud (RM)-fly ash (FA) mass ratio and curing age increased, the strength and structural compactness of the solidified body also increased. The best curing effect was achieved with an RM-FA mass ratio of 7:3 after curing for 90 days. The equivalent circuit model of the solidified body obtained by EIS was R s (Q 1 (R ct1 W) Q 2 R ct2 ). The pore solution resistance R s , solid-liquid interface ion transfer resistance Rct 1, and unconfined compressive strength (UCS) q u all showed an increasing trend with increasing RM-FA mass ratio and increasing curing time. Fitting the model demonstrated that both R s and R ct1 were closely correlated with the strength of the solidified bodies. These conclusions were further verified by scanning electron microscope (SEM) experiments. Overall, this work demonstrates that the strength characteristics of solidified bodies can be evaluated by EIS and reveals the microscopic mechanism of the solidification of Cu 2+ -contaminated soil., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Preliminary evidence indicates that natural disasters are associated with an increased risk for schizophrenia. With few longitudinal studies on earthquakes, this retrospective cohort study examined exposure to the 1976 Tangshan earthquake and the subsequent risk of schizophrenia. Population counts and visits to all nine psychiatric hospitals in Tangshan city were collected. We created three cohort groups by earthquake exposure: infant (August 1972 to July 1976 births), fetal (August 1976 to May 1977 births), and unexposed (June 1977 to May 1981 births). The cumulative incidence of schizophrenia in each cohort was calculated by dividing the number of schizophrenia patients by total births in the corresponding period. Altogether, 6424 schizophrenia patients were identified, with 2786 in the infant group, 663 in the fetal group, and 2975 in the unexposed group. The crude cumulative incidence of schizophrenia in the infant, fetal and unexposed groups were 7.64 (95% confidence interval [CI] = 7.36-7.92), 9.07 (95% CI = 8.38-9.76), and 7.40 (95% CI = 7.13-7.66) per thousand population respectively. Adjusted for mortality, the corresponding figures were 7.73 (95% CI = 7.44-8.01), 9.30 (95% CI = 8.60-10.01) and 7.44 (95% CI = 7.18-7.71) per thousand population respectively. The mortality-adjusted risk ratio (aRR) was 1.25 (95% CI = 1.15-1.36) between fetal and unexposed groups (χ 2  = 27.31, P < 0.001). Males exposed as infants did not differ from the unexposed in cumulative schizophrenia incidence. People with fetal exposure to the 1976 earthquake had 25% higher risk of developing schizophrenia compared to unexposed counterparts., (© 2022. The Author(s).)

Background: The role of psychosocial stressors in psychiatric disorders and executive dysfunction has been reported, separately. The literature has also suggested the involvement of social support and coping strategies in these relationships. However, there is a lack of research conducted to examine the relationships among multiple stressors and neuropsychiatric comorbidities while considering the presence of social support and coping strategies. This study aims to articulate the roles of multiple psychosocial stressors, social support, and coping strategies in the subsequent occurrence of neuropsychiatric comorbidities., Methods: Data analyzed were from the 6th data collection of a large-scale, longitudinal population-based cohort from Southwest Montreal in Canada. The cumulative effects of multiple stressors were separately examined by a composite score and latent profile analysis. Multinomial logistic regression models were used to test the relationship between cumulative stressors and neuropsychiatric comorbidities., Results: A total of 210 participants were included in the analyses. The LPA identified a 2-class model for psychosocial stressors (low and high) and executive function (executive dysfunction and no executive dysfunction), respectively. There were 11.8% of participants with neuropsychiatric comorbidities. Both the composite stress score (RR = 1.08, 95%CI = 1.01-1.15) and latent stress groups (RR = 3.65, 95%CI = 1.15-11.57) were associated with neuropsychiatric comorbidities after adjusting for social support and coping strategies. The risk of developing neuropsychiatric comorbidities decreased when the level of social support was high (P < 0.05)., Conclusions: Exposures to multiple stressors increased the risk of subsequent neuropsychiatric comorbidities, but the risk can be modified by a higher level of social support., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Circulating tumor cells (CTCs) have the characteristics of cancer stem cells and play an important role in the recurrence and metastasis of tumors. CD44 is a surface marker molecule for gastric cancer stem cells (GCSCs) and can be used to identify and isolate GCSCs. Here, we investigated the effect of CD44 protein expression, circulating tumor cells, and CD44-positive CTCs on the prognosis of gastric cancer (GC)., Material and Methods: Blood samples from 58 GC patients being treated at the First Affiliated Hospital of Anhui Medical University from August 2015 to October 2016 were obtained before surgery. The cancer tissues from 58 GC patients after surgery and the same amount of adjacent normal tissues 5 cm away from the center of the cancer tissues were collected as controls. Immunohistochemistry was used to detect CD44 expression in cancer tissues and adjacent normal tissues. Immunomagnetically negative enrichment combined with im-FISH was used to detect CTCs and CD44-positive CTCs in gastric cancer patients., Results: Circulating tumor cells were detected in 44 of 58 patients, and CD44 protein was positive in 34 cases of GC. The presence of CTCs and CD44 is significantly associated with depth of tumor infiltration, lymph node metastasis, TNM stage, and recurrence ( p < 0.01). Twenty-nine of 44 CTC-positive patients had CD44-positive CTCs. The patients with CD44-positive CTCs were more likely to develop recurrence than patients with CD44-negative CTCs ( p < 0.01). Furthermore, 28 of 29 patients with CD44-positive CTCs developed recurrent disease, and the mean time to recurrence was shorter than that in patients with CD44-negative CTCs (16.030 ±5.268 and 21.800 ±4.601 months; p < 0.01). The Cox proportional hazards model indicated that the presence of CD44-positive CTCs and TNM stage were independent predictors of recurrence for GC ( p = 0.044 and 0.035)., Conclusions: The detection of stem cell characteristics of GC CTCs can provide more prognostic information than simply detecting GC CTCs and GC CD44 expression., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

Background: Painful physical symptoms (PPS) are common in patients with major depressive disorder (MDD), but their prevalence has been mixed. This is a systematic review and meta-analysis of the pooled prevalence of PPS in MDD patients., Methods: Systematic literature searches were independently conducted in major databases (PubMed, EMBASE, PsycINFO and Web of Science). Data analyses were conducted using a random-effects model., Results: A total of 20 studies with 53,852 patients were included. The overall prevalence of PPS in MDD patients was 55.2% (95%CI: 47.9-62.3%), with a point prevalence of 64.2% (95%CI: 53.2-73.8%) and a 12-month prevalence of 57.0% (95%CI: 23.9-84.8%). No significant publication bias was found in this meta-analysis., Conclusion: PPS are common in MDD patients. Considering the negative impact of PPS on daily functioning, effective preventive measures and routine screening should be conducted for MDD patients, and timely treatments should be offered to those in need. Registration number: CRD42020179471., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Glioblastoma is one of the most difficult to treat cancers with poor prognosis and survival of around one year from diagnosis. Effective treatments are desperately needed. This work aims to prepare temozolomide acid (TMZA) loaded albumin nanoparticles, for the first time, to target glioblastoma (GL261) and brain cancer stem cells (BL6). TMZA was loaded into human serum albumin nanoparticles (HSA NPs) using the desolvation method. A response surface 3-level factorial design was used to study the effect of different formulation parameters on the drug loading and particle size of NPs. The optimum conditions were found to be: 4 mg TMZA with 0.05% sodium cholate. This yielded NPs with particle size and drug loading of 111.7 nm and 5.5% respectively. The selected formula was found to have good shelf life and serum stability but with a relatively fast drug release pattern. The optimized NPs showed excellent cellular uptake with ∼ 50 and 100% of cells were positive for NP uptake after 24 h incubation with both GL261 and BL6 glioblastoma cell lines, respectively. The selected formula showed high cytotoxicity with ̴ 20% cell viability at 1 mM TMZA after 72 h incubation time. Finally, the fluorescently labelled NPs showed co-localization with the bioluminescent syngeneic BL6 intra-cranial tumour mouse model after intravenous administration., (Copyright © 2021. Published by Elsevier B.V.)

Fibrocartilage enthesis is the junction between bone and tendon with a typical characteristics of fibrocartilage transition zones. The regeneration of this transition zone is the bottleneck for functional restoration of bone tendon junction (BTJ). Biomimetic approaches, especially decellularized extracellular matrix (ECM) materials, are strategies which aim to mimic the components of tissues to the utmost extent, and are becoming popular in BTJ healing because of their ability not only to provide scaffolds to allow cells to attach and migrate, but also to provide a microenvironment to guide stem/progenitor cells lineage-specific differentiation. However, the cellular and molecular mechanisms of those approaches, especially the ECM proteins, remain unclear. For BTJ reconstruction, fibrocartilage regeneration is the key for good integrity of bone and tendon as well as its mechanical recovery, so the components which can guide stem cells to a chondrogenic commitment in biomimetic approaches might well be the key for fibrocartilage regeneration and eventually for the better BTJ healing. In this review, we firstly discuss the importance of cartilage-like formation in the healing process of BTJ. Next, we explore the possibility of tendon-derived stem/progenitor cells as cell sources for BTJ regeneration due to their multi-differentiation potential. Finally, we summarize the role of extracellular matrix components of BTJ in guiding stem cell fate to a chondrogenic commitment, so as to provide cues for understanding the mechanisms of lineage-specific potential of biomimetic approaches as well as to inspire researchers to incorporate unique ECM components that facilitate BTJ repair into design., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Cardiac sialylation is involved in a variety of physiological processes in the heart. Altered sialylation has been implicated in heart failure (HF) mice. However, its role in patients with HF is unclear, and the potential effect of modulation of cardiac sialylation is worth exploring., Methods: We first assessed the association between plasma N-acetylneuraminic acid levels and the incidence of adverse cardiovascular events in patients with HF over a median follow-up period of 2 years. Next, immunoblot analysis and lectin histochemistry were performed in cardiac tissue to determine the expression levels of neuraminidases and the extent of cardiac desialylation. Finally, the therapeutic impact of a neuraminidase inhibitor was evaluated in animal models of HF., Results: Among 1699 patients with HF, 464 (27%) died of cardiovascular-related deaths or underwent heart transplantation. We found that the elevated plasma N-acetylneuraminic acid level was independently associated with a higher risk of incident cardiovascular death and heart transplantation (third tertile adjusted hazard ratio, 2.11 [95% CI, 1.67-2.66], P <0.001). In addition, in cardiac tissues from patients with HF, neuraminidase expression was upregulated, accompanied by desialylation. Treatment with oseltamivir, a neuraminidase inhibitor, in HF mice infused with isoproterenol and angiotensin II significantly inhibited desialylation and ameliorated cardiac dysfunction., Conclusions: This study uncovered a significant association between elevated plasma N-acetylneuraminic acid level and an increased risk of a poor clinical outcome in patients with HF. Our data support the notion that desialylation represents an important contributor to the progression of HF, and neuraminidase inhibition may be a potential therapeutic strategy for HF.

Multiple successful vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to address the ongoing coronavirus disease 2019 (Covid-19) pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein coadministered with CpG adjuvant. To enhance the immunogenicity of our formulation, both antigen and adjuvant were encapsulated with our proprietary artificial cell membrane (ACM) polymersome technology. Structurally, ACM polymersomes are self-assembling nanoscale vesicles made up of an amphiphilic block copolymer comprising poly(butadiene)- b -poly(ethylene glycol) and a cationic lipid, 1,2-dioleoyl-3-trimethylammonium-propane. Functionally, ACM polymersomes serve as delivery vehicles that are efficiently taken up by dendritic cells (DC1 and DC2), which are key initiators of the adaptive immune response. Two doses of our formulation elicit robust neutralizing antibody titers in C57BL/6 mice that persist at least 40 days. Furthermore, we confirm the presence of functional memory CD4 + and CD8 + T cells that produce T helper type 1 cytokines. This study is an important step toward the development of an efficacious vaccine in humans.

Immune checkpoint blockade involves targeting immune regulatory molecules with antibodies. Preclinically, complex multiantibody regimes of both inhibitory and stimulatory targets are a promising candidate for the next generation of immunotherapy. However, in this setting, the antibody platform may be limited due to excessive toxicity caused by off target effects as a result of systemic administration. RNA can be used as an alternate to antibodies as it can both downregulate immunosuppressive checkpoints (siRNA) or induce expression of immunostimulatory checkpoints (mRNA). In this study, we demonstrate that the combination of both siRNA and mRNA in a single formulation can simultaneously knockdown and induce expression of immune checkpoint targets, thereby reprogramming the tumor microenvironment from immunosuppressive to immunostimulatory phenotype. To achieve this, RNA constructs were synthesized and formulated into stable nucleic acid lipid nanoparticles (SNALPs); the SNALPs produced were 140-150 nm in size with >80% loading efficiency. SNALPs could transfect macrophages and B16F10 cells in vitro resulting in 75% knockdown of inhibitory checkpoint (PDL1) expression and simultaneously express high levels of stimulatory checkpoint (OX40L) with minimal toxicity. Intratumoral treatment with the proposed formulation resulted in statistically reduced tumor growth, a greater density of CD4+ and CD8+ infiltrates in the tumor, and immune activation within tumor-draining lymph nodes. These data suggest that a single RNA-based formulation can successfully reprogram multiple immune checkpoint interactions on a cellular level. Such a candidate may be able to replace future immune checkpoint therapeutic regimes composed of both stimulatory- and inhibitory-receptor-targeting antibodies.

Little is known about the epidemiology of schizophrenia in the agricultural regions of China. This study examined the 1-month and lifetime prevalence of schizophrenia and their association with socio-demographic factors in Hebei province which is an important agricultural region of China. A multi-stage, stratified, cluster random sampling method was adopted. The diagnosis of schizophrenia was ascertained with the validated Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition (SCID-I/P/C). Altogether, 23,675 subjects were screened, of whom, 20,884 were included for analyses. The weighted 1-month and lifetime prevalence of schizophrenia were 0.5 % [95 % confidence interval (CI): 0.4-0.5 %] and 0.6 % (95 %CI: 0.5-0.7 %), respectively. Multiple logistic regression analyses found that unmarried marital status [P < 0.001, Odd Ratio(OR)=2.670, 95 %CI:1.767-4.036], lower education level (primary school or below: P = 0.042, OR=2.447, 95 % CI: 1.034-5.933; secondary school: P = 0.002, OR = 4.261, 95 % CI:1.692-10.730), unemployment (P = 0.006, OR=1.870, 95 % CI:1.198-2.920), lower income (P < 0.001, OR=4.017, 95 % CI:2.207-7.310) and family history of psychiatric disorders (P < 0.001, OR=16.278, 95 % CI:10.435-25.393) were independently associated with a higher risk of schizophrenia, while age above 60 years (P = 0.004, OR=0.440, 95 % CI:0.253-0.765) was associated with a lower risk of schizophrenia. The prevalence of schizophrenia appeared to be lower in Hebei province compared to other regions of China or other countries. Socioeconomic factors should be further examined to inform the public health surveillance and policies relevant to schizophrenia in the agricultural regions of China., (Copyright © 2021. Published by Elsevier B.V.)

microRNA (miRs or miRNAs) is a type of non-coding RNA which plays the role of a regulator in gene expression. A number of miRNAs has been found by the researchers for its critical role in the pathogenesis of polycystic ovary syndrome (PCOS). But there is a no clear information available about the biological role played by miR-21 in PCOS prognosis. So, the aim of the current study is to determine the role played by miR-21 in the progression of PCOS. In order to achieve this aim, the researcher examined miR-21 expression levels in ovarian tissue samples collected from PCOS patients as well as their KGN cells (human granulosa-like tumor cell line). The study results inferred downregulation in the expression levels of miR-21 in ovarian tissues of PCOS patients and KGN cells, when compared with unaffected ovarian tissues and IOSE80 (human ovarian surface epithelial cell line). With the overexpression of miR-21, the proliferation of KGN cells was prevented and apoptosis was induced among these cells. The authors used StarBase analysis for predicting the direct binding target of miR-21. As per the assay results attained from luciferase reporter assay and western blot analysis, it was found that SNHG7 acted as a target gene for miR-21 while the latter downregulated the former. To conclude, the current study revealed the contribution of miR-21/SNHG7 axis in the regulation of Granulosa Cell (GC) proliferation and apoptosis. It further suggested a new molecular mechanism for GC dysregulation while the finding presents a new promising target for PCOS treatment procedure., (Copyright © 2021. Published by Elsevier B.V.)

The isomerization of glucose to fructose provides an important way to expand the utilization of biomass. Herein, an amidoximated polyacrylonitrile (PAO) with an amidoxime functional group was prepared and used as an active heterogeneous catalyst for the isomerization of glucose to fructose. The PAO was characterized by SEM, XPS, and FTIR. The yield of fructose reached 48.9% with a selectivity of 98.6% for a 5 h reaction in aqueous solution at an initial pH of 6.5 and 85 °C. The pH caused a great influence on the conversion of glucose and selectivity of fructose while a little effect on the yield of fructose in the range of pH 5-10. The activation energy of isomerization reaction was evaluated as 79.7 kJ·mol -1 . The catalysis mechanism was proposed, and the synergistic effect of oxime and amino groups played an important role in the isomerization of glucose. PAO maintained good catalytic activity after four cycles., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Prevalence estimates of major depressive disorder (MDD) among adults in China have varied widely between studies. In this systematic review and meta-analysis, the overall prevalence of MDD in the Chinese population was estimated from published epidemiological studies and potential moderators that account for variability in estimates were assessed. Methods: A systematic literature search was conducted in PubMed, EMBASE, Web of Science, PsycINFO, China National Knowledge Internet (CNKI), and WanFang databases to identify relevant studies. Data analyses were conducted using the Comprehensive Meta-Analysis Version 2.0. Results: Forty studies comprising 1,024,087 subjects were included. The pooled point, 12-month, and lifetime prevalence rates of MDD in China were 1.1% (95% CI: 0.9-1.4%), 1.6% (95% CI: 1.0-2.5%), and 1.8% (95% CI: 1.5-2.2%), respectively. Subgroup and meta-regression analyses revealed gender, marital status, survey year, being published in English language, use of the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic systems and age as significant moderators of MDD prevalence. Conclusion: The overall prevalence of MDD in the Chinese population appears to be lower than that of most countries, but the rates have been increasing over time and are elevated in particular demographic subgroups. Due to the negative consequences of MDD, effective preventive measures, early identification, and timely treatments are still important and should be offered to those in need., 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 Zhao, Jin, Rao, Zhang, Zhang, Jackson, Su, Xiang, Yuan and Xiang.)

Background: The impact of concomitant impairments of left and right ventricular (LV and RV) strain on the long-term prognosis of acute ST-elevation myocardial infarction (STEMI) is not clear. Methods: We analyzed CMR images and followed up 420 first STEMI patients from the EARLY Assessment of MYOcardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). These patients received timely primary percutaneous coronary intervention (PCI) within 12 h and CMR examination within 1 week (median, 5 days; range, 2-7 days) after infarction. Global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of both ventricles were measured based on CMR cine images. Conventional CMR indexes were also assessed. Primary clinical outcome was composite major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, re-hospitalization for heart failure and stroke. In addition, CMR data from 40 people without apparent heart disease were used as control group. Results: Compared to controls, both LV and RV strains were remarkably reduced in STEMI patients. During follow-up (median: 52 months, interquartile range: 29-68 months), 80 patients experienced major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, heart failure, and stroke. LV-GCS > -11.20% was an independent predictor of MACCEs ( P < 0.001). RV-GRS was the only RV strain index that could effectively predict the risk of MACCEs (AUC = 0.604, 95% CI [0.533, 0.674], P = 0.004). Patient with RV-GRS ≤ 38.79% experienced more MACCEs than those with preserved RV-GRS (log rank P < 0.001). Moreover, patients with the concomitant decrease of LV-GCS and RV-GRS were more likely to experience MACCEs than patients with decreased LV-GCS alone (log rank P = 0.010). RV-GRS was incremental to LV-GCS for the predictive power of MACCEs (continuous NRI: 0.327; 95% CI: 0.095-0.558; P = 0.006). Finally, tobacco use ( P = 0.003), right coronary artery involvement ( P = 0.002), and LV-GCS > -11.20% ( P = 0.012) was correlated with lower RV-GRS. Conclusions: The concomitant decrease of LV and RV strain is associated with a worse long-term prognosis than impaired LV strain alone. Combination assessment of both LV and RV strain indexes could improve risk stratification of patients with STEMI. Trial Registration: ClinicalTrials.gov, NCT03768453. Registered 7 December 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03768453., 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 Lai, Jie, Jian-Xun, Ling-Cong, Jun-Tong, Bo-Zhong, Dong-Ao-Lei, Bing-Hua, Song, Zheng, Fan, Yi-Ning, Fu-Hua, Jian-Cheng, Hu-Wen, Jian-Rong, Heng and Jun.)

The coronavirus disease 2019 (COVID-19) and Severe Acute Respiratory Syndrome (SARS) are associated with various psychiatric comorbidities. This is a systematic review and meta-analysis comparing the prevalence of psychiatric comorbidities in all subpopulations during the SARS and COVID-19 epidemics. A systematic literature search was conducted in major international (PubMed, EMBASE, Web of Science, PsycINFO) and Chinese (China National Knowledge Internet [CNKI] and Wanfang) databases to identify studies reporting prevalence of psychiatric comorbidities in all subpopulations during the SARS and COVID-19 epidemics. Data analyses were conducted using the Comprehensive Meta-Analysis Version 2.0 (CMA V2.0). Eighty-two studies involving 96,100 participants were included. The overall prevalence of depressive symptoms (depression hereinafter), anxiety symptoms (anxiety hereinafter), stress, distress, insomnia symptoms, post-traumatic stress symptoms (PTSS) and poor mental health during the COVID-19 epidemic were 23.9% (95% CI: 18.4%-30.3%), 23.4% (95% CI: 19.9%-27.3%), 14.2% (95% CI: 8.4%-22.9%), 16.0% (95% CI: 8.4%-28.5%), 26.5% (95% CI: 19.1%-35.5%), 24.9% (95% CI: 11.0%-46.8%), and 19.9% (95% CI: 11.7%-31.9%), respectively. Prevalence of poor mental health was higher in general populations than in health professionals (29.0% vs. 11.6%; Q=10.99, p=0.001). The prevalence of depression, anxiety, PTSS and poor mental health were similar between SARS and COVID-19 epidemics (all p values>0.05). Psychiatric comorbidities were common in different subpopulations during both the SARS and COVID-19 epidemics. Considering the negative impact of psychiatric comorbidities on health and wellbeing, timely screening and appropriate interventions for psychiatric comorbidities should be conducted for subpopulations affected by such serious epidemics., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Past suicide attempts (SA) are a major contributor to suicide. The prevalence of SA in pregnant and postpartum women varied significantly across studies. Therefore, this meta-analysis was conducted to examine the prevalence of SA and its mediating factors in this population., Methods: Relevant articles published in PubMed, EMBASE, Web of Science, PsycINFO, Medline complete, Chinese National Knowledge Infrastructure database (CNKI), Chinese Wanfang and Chongqing VIP database were systematically searched from inception to March 28, 2019. Titles, abstracts and full texts were reviewed independently by three researchers. Studies were included if they reported data on SA prevalence or provided relevant data that enabled the calculation of SA prevalence. Data were extracted by two researchers and checked by one senior researcher. The random-effects model was used to analyze data by the CMA 2.0 and Stata 12.0, with the high degree of statistical heterogeneity present. The primary outcomes were prevalence of SA with 95% CI during pregnancy and during the first-year postpartum., Results: Fourteen studies covering 6,406,245 pregnant and postpartum women were included. The pooled prevalence of SA was 680 per 100,000 (95% confidence interval 0.10-4.69%) during pregnancy and 210 per 100,000 (95% confidence interval 0.01-3.21%) during the first-year postpartum. Data source was significantly associated with prevalence of SA in the subgroup analysis (pregnancy, p < 0.001; the first-year postpartum, p = 0.013)., Conclusion: The prevalence of SA is not high in pregnant and postpartum women. Due to the potential loss of life and negative impact of SA on health outcomes, however, careful screening and effective preventive measures should be implemented for this population.

Objective: To explore the kinematic biomechanical changes and symmetry in the left and right sides of the facet joints of lumbar spine segments under different functional loads., Methods: Participants (n = 10) performing standing flexion and extension movements were scanned using computed tomography (CT) and dual fluoroscopy imagine system. Instantaneous images of the L 3 -S 1 vertebrae were captured, and by matching a three-dimensional CT model with contours from dual fluoroscopy images, in vivo facet joint movements were reproduced and analyzed. Translations and rotations of lumbar vertebral (L 3 and L 4 ) facet joints of data were compared for different loads (0, 5, 10 kg). The participants performed flexion and extension movements in different weight-bearing states, the translations and angles changes were calculated respectively., Results: From standing to extension, there were no statistical differences in rotation angles for the facet joint processes of different vertebral segment levels under different weight loads (P > 0.05). Mediolateral axis and cranio-caudal translations under different weight loads were not statistically different for vertebral segment levels (P > 0.05). Anteroposterior translations for L 3 (1.4 ± 0.1 mm) were greater than those for L 4 (1.0 ± 0.1 mm) under the different load conditions (P = 0.04). Bilaterally, mediolateral, anteroposterior, and cranio-caudal translations of the facet joints under different weights (0, 10 kg) for each segment level (L 3 and L 4 ) were symmetric (P > 0.05). From flexion to standing, there were no statistical differences in rotation angles for different weights (0, 5, 10 kg) for each level (L 3 and L 4 ) (P > 0.05). There were no statistical differences between mediolateral, anteroposterior, and cranio-caudal translations at each segment level (L 3 and L 4 ) under different loads (P > 0.05). Under the condition of no weight (0 kg), L 3 mediolateral translations on the left side (1.7 ± 1.6 mm) were significantly greater (P = 0.03) than those on the right side (1.6 ± 1.6 mm). Left side (1.0 ± 0.7 mm) L 4 mediolateral translations were significantly smaller (P = 0.03) than those on the right side (1.1 ± 0.7 mm). There were no statistical differences between different weights for either anteroposterior and cranio-caudal translations (P > 0.05). There were no statistical differences for mediolateral, anteroposterior, and cranio-caudal translations for 10 kg (P > 0.05)., Conclusion: Lumbar spine facet joint kinematics did not change significantly with increased loads. Anteroposterior translations for L 3 were greater than those for L 4 of the vertebral segments are related to the coronal facet joint surface. Changes in facet surface symmetry indicates that the biomechanical pattern between facet joints may change., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: Constipation is a common but often ignored side effect of antipsychotic treatment, although it is associated with adverse outcomes. The results of the efficacy and safety of traditional Chinese herbal medicine (TCM) in treating constipation are mixed across studies. This is a systematic review and meta-analysis of randomized controlled trials (RCTs) of the efficacy and safety of TCM compared to Western medicine (WM) in treating antipsychotic-related constipation. Methods: Major international electronic (PubMed, EMBASE, Cochrane Library, and Web of Science) and Chinese (Wanfang, WeiPu VIP, SinoMed, and CNKI) databases were searched from their inception to November 29, 2020. Meta-analysis was performed using the random-effects model. Results: Thirty RCTs with 52 arms covering 2,570 patients in the TCM group and 2,511 patients in the WM group were included. Compared with WM, TCM alone was superior regarding the moderate response rate [risk ratio (RR) = 1.165; 95% confidence interval (CI): 1.096-1.238; P < 0.001], marked response rate (RR = 1.437; 95% CI: 1.267-1.692; P < 0.001), and remission rate (RR = 1.376; 95% CI: 1.180-1.606; P < 0.001) for constipation, while it was significantly associated with lower risk of rash (RR = 0.081; 95% CI: 0.019-0.342; P = 0.001). For the moderate response rate, meta-regression analyses revealed that publication year (β = -0.007, P = 0.0007) and Jadad score (β = 0.067, P < 0.001) significantly moderated the results. For the remission rate, subgroup and meta-regression analyses revealed that the geographical region ( P = 0.003), inpatient status ( P = 0.035), and trial duration (β = 0.009, P = 0.013) significantly moderated the results. Conclusions: The efficacy of TCM for antipsychotic-related constipation appeared to be greater compared to WM, while certain side effects of TCM, such as rash, were less frequent., 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. The reviewer XW declared a shared affiliation, though no other collaboration, with several of the authors, HQ, SS, and LZ, to the handling Editor. The reviewer QL declared a shared affiliation, though no other collaboration, with several of the authors, HQ, SS, and LZ, to the handling Editor., (Copyright © 2021 Rao, Yang, Qi, Sha, Zheng, Zhang, Ungvari, Ng and Xiang.)

The ability to track extracellular vesicles (EVs) in vivo without influencing their biodistribution is a key requirement for their successful development as drug delivery vehicles and therapeutic agents. Here, we evaluated the effect of five different optical and nuclear tracers on the in vivo biodistribution of EVs. Expi293F EVs were labeled using either a noncovalent fluorescent dye DiR, or covalent modification with 111 indium-DTPA, or bioengineered with fluorescent (mCherry) or bioluminescent (Firefly and NanoLuc luciferase) proteins fused to the EV marker, CD63. To focus specifically on the effect of the tracer, we compared EVs derived from the same cell source and administered systemically by the same route and at equal dose into tumor-bearing BALB/c mice. 111 Indium and DiR were the most sensitive tracers for in vivo imaging of EVs, providing the most accurate quantification of vesicle biodistribution by ex vivo imaging of organs and analysis of tissue lysates. Specifically, NanoLuc fused to CD63 altered EV distribution, resulting in high accumulation in the lungs, demonstrating that genetic modification of EVs for tracking purposes may compromise their physiological biodistribution. Blood kinetic analysis revealed that EVs are rapidly cleared from the circulation with a half-life below 10 min. Our study demonstrates that radioactivity is the most accurate EV tracking approach for a complete quantitative biodistribution study including pharmacokinetic profiling. In conclusion, we provide a comprehensive comparison of fluorescent, bioluminescent, and radioactivity approaches, including dual labeling of EVs, to enable accurate spatiotemporal resolution of EV trafficking in mice, an essential step in developing EV therapeutics.

With a dismal survival rate, pancreatic cancer (PC) remains one of the most aggressive and devastating malignancies, predominantly due to the absence of a valid biomarker for diagnosis and limited therapeutic options for advanced diseases. Exosomes (Exo) as cell-derived vesicles, are widely used as natural nanocarriers for drug delivery. P21-activated kinase 4 (PAK4) is oncogenic when overexpressed, promoting cell survival, migration and anchorage-independent growth. Herein we validated PAK4 as a therapeutic target in an in vivo PC tumour mouse model using Exo-mediated RNAi following intra-tumoural administration. PC derived Exo were firstly isolated by ultracentrifugation on sucrose cushion and characterised for their surface marker expression, size, number, purity and morphology. SiRNA was encapsulated into Exo via electroporation and dual uptake of Exo and siRNA was investigated by flow cytometry and confocal microscopy. In vitro siPAK4 silencing in PC cells following uptake was assessed by flow cytometry, western blotting, and in vitro scratch assay. In vivo efficacy (tumour growth delay and mouse survival) of siPAK4 was evaluated in PC bearing NSG mouse model. Ex vivo tumours were examined using Haematoxylin and eosin (H&E) staining and immunohistochemistry. Results showed high quality PC-derived PANC-1 Exo were obtained. SiRNA was incorporated in Exo with 16.5% encapsulation efficiency. In vitro imaging confirmed Exo and siRNA co-localisation in cells. PAK4 knockdown was successful with 30 nM Exo-siPAK4 at 24 h post incubation in vitro. Intra-tumoural administration of Exo-siPAK4 (0.03 mg/kg siPAK4 and 6.1 × 10 11 Exo, each dose, two doses) reduced PC tumour growth in vivo and enhanced mice survival (p < 0.001), with minimal toxicity observed compared to polyethylenimine (PEI) used as a commercial transfection reagent. H&E staining of tumours showed significant tissue apoptosis in siPAK4 treated groups. PAK4 knockdown prolongs survival of PC-bearing mice suggesting its potential as a new therapeutic target for PC. PANC-1 Exo demonstrated comparable efficacy but safer profile than PEI as in vivo RNAi transfection reagent., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In this work, a novel enteric coating based on natural waxes and alginate was reported. Initially, theophylline tablets were coated with emulsified ceresin wax in heated aqueous alginate solution using a fluidised bed coating technology. A coating level of 10% proved sufficient to prevent tablets from uptaking gastric medium (<5%) and produced a delayed release profile that complies to the pharmacopeial criteria of enteric coating release. Then, a wide range of emulsions based on other natural waxes (white beeswax, yellow beeswax, cetyl palmitate, carnauba wax or rice bran wax) yielded coatings with similar disintegration times and release profiles. Interestingly, the ceresin-based coating showed a superior performance at inhibiting acid uptake and enabling highly pH-responsive drug release in comparison to different commercially available GRAS enteric coating products (Eudraguard® Control, Swanlac® ASL10, and Aquateric™ N100). The coating was stable for 6 months at 30 °C and 65% RH. This innovative approach of applying hot O/W emulsion of natural waxes yielded an aesthetically attractive and stable coating with gastric protection and pH-sensitive release properties. The novel coating can be an efficient and promising alternative to overcome the shortcomings of current GRAS grade enteric coating products., (Copyright © 2020. Published by Elsevier B.V.)

This is a meta-analysis of randomized controlled trials (RCTs) comparing cognitive behaviour therapy for insomnia (CBT-I) monotherapy with active control treatment for insomnia in patients with medical or psychiatric comorbidities. Both international (PubMed, EMBASE, PsycINFO, Cochrane Library) and Chinese (WanFang, and CNKI) databases were systematically searched. The random effects model was used. Thirteen RCTs comparing CBT-I (n = 441) and active controls (n = 412) groups were included. CBT-I group showed significant advantage over active controls at post-treatment assessment in terms of Insomnia Severity Index (ISI; SMD = -0.74), sleep onset latency (SMD = -0.36), wake after sleep onset (SMD = -0.21), sleep quality (SMD = 0.56), Pittsburgh sleep quality index total scores (PSQI; SMD = -0.76) and the total score of dysfunctional beliefs and attitudes about sleep scale (DBAS; SMD = -1.09). Subgroup analyses revealed significant improvement in sleep onset latency in patients with psychiatric disorders (SMD = -0.45), while significant reduction of number of wakeup after sleep onset was found in patients with medical conditions (SMD = -0.31). This meta-analysis found that CBT-I monotherapy had greater efficacy than other active control treatment for insomnia in patients with medical or psychiatric comorbidities.

Objective: Poor mental health is associated with impaired social functioning, lower quality of life, and increased risk of suicide and mortality. This study examined the prevalence of poor general mental health among older adults (aged 65 years and above) and its sociodemographic correlates in Hebei province, which is a predominantly agricultural area of China. Methods: This epidemiological survey was conducted from April to August 2016. General mental health status was assessed using the 12-item General Health Questionnaire (GHQ-12). Results: A total of 3,911 participants were included. The prevalence of poor mental health (defined as GHQ-12 total score ≥ 4) was 9.31% [95% confidence interval (CI): 8.4-10.2%]. Multivariable logistic regression analyses found that female gender [ P < 0.001, odds ratio (OR) = 1.63, 95% CI: 1.29-2.07], lower education level ( P = 0.048, OR = 1.33, 95% CI: 1.00-1.75), lower annual household income ( P = 0.005, OR = 1.72, 95% CI: 1.17-2.51), presence of major medical conditions ( P < 0.001, OR = 2.95, 95% CI: 2.19-3.96) and family history of psychiatric disorders ( P < 0.001, OR = 3.53, 95% CI: 2.02-6.17) were significantly associated with poor mental health. Conclusion: The prevalence of poor mental health among older adults in a predominantly agricultural area was lower than findings from many other countries and areas in China. However, continued surveillance of mental health status among older adults in China is still needed., (Copyright © 2020 Jin, Zhang, Zhang, Rao, Zhang, Cui, Li, Li, Ungvari, Jackson, Li and Xiang.)

The plants of the Trigonostemon sp. genus(Euphorbiaceae family) comprising about 50 species worldwide are mainly distributed in tropical and subtropical Asia, 10 species of which can be found in southern of China. Phytochemical studies on the plants in the genus have demonstrated a large amount of terpenoids and alkaloids. Modern pharmacological studies have demonstrated cytotoxicity, antivirus, antibacterial, anti-inflammation and other pharmacological activities. In this paper, chemical compositions and biological activities of Trigonostemon genus at home and abroad over the past decade were summarized, in order to provide scientific basis for the further development and utilization of Trigonostemon plants.

Hypoxia-inducible factors(HIFs)are the key transcription factors that sense and regulate cellular oxygen concentration in vivo. HIF-1 is composed of 2 subunits,α and β,in which,the molecular regulatory mechanism of HIF-1α involves the main processes of its degradation and activation. The degradation of HIF-1α is regulated by oxygen-dependent pathways,including &quot;von hippel-lindau protein(pVHL)-dependent pathway&quot; and &quot;pVHL-independent pathway&quot;. The activation of HIF-1α is regulated by oxygen-independent pathways,including mammalian target of rapamycin(mTOR)/eukaryotic initiation factor 4 E-binding protein 1(4 EBP1)/HIF-1α pathway,phosphatidylinositol 3-kinase(PI3 K)/proteirrserinc-threonine kinases(Akt)/HIF-1α pathway and silent information regulator1(Sirt1)/HIF-1α pathway. In recent years,based on the molecular regulatory mechanism of HIFs,Roxadustat,a new drug for the treatment of renal anemia has been developed. Besides, some macromolecular substances with similar pharmacological effect to HIFs have been found in the extracts from Chinese herbal medicine(CHM),such as emodin,notoginseng triterpenes,honokiol and clematichinenoside. These natural macromolecular substances play the regulatory roles in inflammatory response,epigenetic modification and auto-phagy. It is worth noting that,for common hypoxic-related diseases including diabetic kidney disease,HIFs-mediated &quot;pyroptosis&quot; may be a new target of CHMs for clearing dampness and heat and its representative classical prescriptions(Ermiao Pills)in treating inflammatory injury in cells and tissues.

Purpose: Poor sleep quality is common in medical students and is associated with a number of negative health outcomes. However, the prevalence estimates of poor sleep quality in medical students vary widely across studies. We thus conducted a meta-analysis of the prevalence of poor sleep quality and its mediating factors in medical students., Methods: A systematic literature search of PubMed, EMBASE, Web of Science, PsycINFO, and Medline Complete was performed. The random-effects model was used to analyze the pooled prevalence of poor sleep quality and its 95% confidence intervals (CIs)., Results: A total of 57 studies with 25,735 medical students were included. The pooled prevalence of poor sleep quality was 52.7% (95% CI: 45.3% to 60.1%) using the Pittsburgh Sleep Quality Index (PSQI). The pooled mean total PSQI score across 41 studies with available data was 6.1 (95% CI: 5.6 to 6.5). Subgroup analyses found that PSQI cutoff value and study region were associated with the prevalence of poor sleep quality (P = 0.0003 VS. P = 0.005). Across the continents, poor sleep quality was most common in Europe, followed by the Americas, Africa, Asia, and Oceania. Meta-regression analyses found that smaller sample size (slope = - 0.0001, P = 0.009) was significantly associated with higher prevalence of poor sleep quality., Conclusions: Poor sleep quality is common among medical students, especially in Europe and the Americas continets. Due to the negative health outcomes, regular screening of poor sleep quality and effective interventions are needed for medical students.