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Zhan-Miao Yi,1–3 Cheng Wen,1,2 Ting Cai,4 Lu Xu,4 Xu-Li Zhong,5 Si-Yan Zhan,4,6 Suo-Di Zhai1,3 1Department of Pharmacy, Peking University Third Hospital, Beijing, China; 2Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Science, Peking University Health Science Center, Beijing, China; 3Institute for Drug Evaluation, Peking University Health Science Center, Beijing, China; 4Department of Epidemiology and Bio-statistics, School of Public Health, Peking University Health Science Center, Beijing, China; 5Department of Pharmacy, Children’s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China; 6Center for Clinical Epidemiology, Peking University Third Hospital, Beijing, China Objective: To evaluate the efficacy, safety and economics of levetiracetam (LEV) for epilepsy. Materials and methods: PubMed, Scopus, the Cochrane Library, OpenGrey.eu and ClinicalTrials.gov were searched for systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), observational studies, case reports and economic studies published from January 2007 to April 2018. We used a bubble plot to graphically display information of included studies and conducted meta-analyses to quantitatively synthesize the evidence. Results: A total of 14,803 records were obtained. We included 30 SRs/meta-analyses, 34 RCTs, 18 observational studies, 58 case reports and 2 economic studies after the screening process. The included SRs enrolled patients with pediatric epilepsy, epilepsy in pregnancy, focal epilepsy, generalized epilepsy and refractory focal epilepsy. Meta-analysis of the included RCTs indicated that LEV was as effective as carbamazepine (CBZ; treatment for 6 months: 58.9% vs 64.8%, OR=0.76, 95% CI: 0.50–1.16; 12 months: 54.9% vs 55.5%, OR=1.24, 95% CI: 0.79–1.93), oxcarbazepine (57.7% vs 59.8%, OR=1.34, 95% CI: 0.34–5.23), phenobarbital (50.0% vs 50.9%, OR=1.20, 95% CI: 0.51–2.82) and lamotrigine (LTG; 61.5% vs 57.7%, OR=1.22, 95% CI: 0.90–1.66). SRs and observational studies indicated a low malformation rate and intrauterine death rate for pregnant women, as well as low risk of cognitive side effects. But psychiatric and behavioral side effects could not be ruled out. LEV decreased discontinuation due to adverse events compared with CBZ (OR=0.52, 95% CI: 0.41–0.65), while no difference was found when LEV was compared with placebo and LTG. Two cost-effectiveness evaluations for refractory epilepsy with decision-tree model showed US$ 76.18 per seizure-free day gained in Canada and US$ 44 per seizure-free day gained in Korea. Conclusion: LEV is as effective as CBZ, oxcarbazepine, phenobarbital and LTG and has an advantage for pregnant women and in cognitive functions. Limited evidence supports its cost-effectiveness. Registered number: PROSPERO (No CRD 42017069367). Keywords: seizure freedom, responder rate, quality of life, malformations, neurological development, psychiatric side effects, cost-effectiveness

Abstract The field emission properties of SnO2nanowires fabricated by chemical vapor deposition with metallic catalyst-assistance were investigated. For the as-fabricated SnO2nanowires, the turn-on and threshold field were 4.03 and 5.4 V/μm, respectively. Considerable enhancement of field emission of SnO2nanowires was obtained by a post-annealing process in oxygen at high temperature. When the SnO2nanowires were post-annealed at 1,000 °C in oxygen, the turn-on and threshold field were decreased to 3.77 and 4.4 V/μm, respectively, and the current density was increased to 6.58 from 0.3 mA/cm2at the same applied electric field of 5.0 V/μm.

Background: Social isolation not only increases the risk of mortality in later life but also causes depressive symptoms, cognitive and physical disabilities. Although RNA m6A modifications are suggested to play key roles in brain development, neuronal signaling and neurological disorders, both the roles of m6A and the enzymes that regulate RNA m6A modification in social isolation induced abnormal behavior is unknown. The present study aims to explore the possible epitranscriptomic role of RNA m6A modifications and its enzymes in social isolation induced impaired behavior., Methods: 3-4 weeks mice experiencing 8 weeks social isolation stress (SI) were used in the present study. We quantified m6A levels in brain regions related to mood and cognitive behavior. And the expression of hippocampal m6A enzymes was also determined. The role of hippocampal m6A and its enzymes in SI induced abnormal behavior was further verified by the virus tool., Results: SI led to not only depressive and anxiety-like behaviors but also cognitive impairment, with corresponding decreases in hippocampal m6A and METTL14. Hippocampal over-expression METTL14 with lentivirus not only rescued these behaviors but also enhanced the hippocampal m6A level. Hippocampal over-expression METTL14 resulted in increased synaptic related genes., Conclusions: We provide the first evidence that post-weaning social isolation reduces hippocampal m6A level and causes altered expression of m6A enzyme in mice. Importantly, hippocampal METTL14 over-expression alleviated the SI-induced depression/anxiety-like and impaired cognitive behaviors and enhanced m6A level and synaptic related genes expression., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest or any known competing financial interests or personal relationships that may bias the performance or interpretation of the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is a malignant tumor that has a high incidence and mortality worldwide. Despite extensive studies, the detailed molecular mechanism of HCC development remains unclear. Studies have shown that the occurrence and development of HCC are closely related to abnormal gene expression. BCAR3 has been shown to be overexpressed in a variety of malignant tumors. However, the role of BCAR3 in HCC remains unclear., Aim: To investigate the expression of BCAR3 and BCAR3 -related competing endogenous RNAs (ceRNAs) in HCC and their clinical significance, in order to provide new ideas for the diagnosis and treatment of HCC., Methods: The data of HCC were obtained from the Cancer Genome Atlas database and The Genotype Tissue Expression, including transcriptome data and clinical information. Multiple common databases, including UALCAN, Timer 2.0, cBioPortal, LinkedOmics, starBase, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, were used to analyse the expression of BCAR3 , prognostic value, genetic alteration, co-expressed genes, differentially expressed genes, BCAR3 gene-related ceRNAs and functional enrichment analysis in HCC patients. Kaplan-Meier analysis, univariate and multivariate Cox regression analysis were used to analyze survival prognosis and the Spearman test was used to measure correlations between BCAR3 and immune functions. And R language package was used to analyze the correlation between BCAR3 and immune invasion of HCC., Results: Our study indicated that BCAR3 was differentially expressed in various tumor tissues. The over-expression of BCAR3 gene was an unfavorable prognostic indicator for HCC patients, and associated with unfavorable cytogenetic risk and gene mutations. Moreover, most immune cells were positively correlated with BCAR3 ( P < 0.05). According to the results of functional enrichment analysis, BCAR3 was involved in the positive regulation of epidermal growth factor receptor signaling pathway and ERBB signaling pathway, and was related to DNA replication and GTPase regulator activity. Finally, our study found that based on RAB30-DT and miR-19b-3p pathways, targeting BCAR3 might promote the occurrence and development of HCC., Conclusion: Collectively, this study indicated that the BCAR3 gene was involved in the occurrence and development of HCC, and it might be a new biomarker and therapeutic target for HCC, but the specific mechanism remains to be further verified., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Childhood and adolescent cancer represent a significant health burden in the United States. Current and precise epidemiological data are crucial to develop effective cancer control plans and ultimately reduce the burden of childhood and adolescent cancer., Methods: We analyzed data obtained from cancer registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Age-standardized incidence and death rates, assessed using joinpoint analysis, were quantified as annual percentage changes (APC) and average percentage changes (AAPC)., Results: The overall cancer incidence rate in 2008-2018 was 187.9 per 1,000,000 persons. Cancer incidence rates demonstrated a sustained upward trend, with an APC of 0.8 from 1975 to 2018. Incidence rates during 2008-2018 remained stable among non-Hispanic Black children but increased among other racial and ethnic groups. Leukemias, central nervous system tumors, and lymphomas were the most common cancer groups for patients aged 0-19 years. Cancer death rates decreased among children [AAPC, -1.3 (95% CI, -1.5 to -1.1)] during 2009-2019, while were stable among adolescents during that period., Conclusions: In this study, we analyzed cancer incidence and mortality rates and trends in children aged 0-19 years in the United States. Our findings revealed an overall increase in cancer incidence rates among children and adolescents, accompanied by a decline in cancer mortality rates over time. These rates and trends varied by age, sex, and particularly race and ethnicity, highlighting the significance of comprehending and addressing disparities and ultimately reducing the disease burden of childhood and adolescent 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., (© 2024 Tang, Jiang, Huang, Shi, Xu, Xu, Peng, Zhang, Shi, Zhong, Kang and Lü.)

Background and Hypothesis: Schizophrenia (SCZ) is a multifaceted mental disorder marked by a spectrum of symptoms, including hallucinations, delusions, cognitive deficits, and negative symptoms. Its etiology involves intricate interactions between genetic and environmental factors, posing significant challenges for effective treatment. We hypothesized that intranasal administration of exosomes derived from nasal olfactory mucosal mesenchymal stem cells (OM-MSCs-exos) could alleviate SCZ-like behaviors in a murine model induced by methylazoxymethanol (MAM)., Study Design: We conducted a comprehensive investigation to assess the impact of intranasally delivered OM-MSC-exos on SCZ-like behaviors in MAM-induced mice. This study encompassed behavioral assessments, neuroinflammatory markers, glial activation, synaptic protein expression, and neurogenesis within the hippocampus., Study Results: Our findings demonstrated that intranasal administration of OM-MSC-exos effectively ameliorated SCZ-like behaviors, specifically addressing social withdrawal and sensory gating deficits in the MAM-induced murine model. Furthermore, OM-MSC-exos intervention yielded a reduction in neuroinflammatory markers and a suppression of microglial activation within the hippocampus. Simultaneously, we observed an upregulation of key synaptic protein expression, including PSD95 and TH, the rate-limiting enzyme for dopamine biosynthesis., Conclusions: Our study underscores the therapeutic potential of OM-MSC-exos in mitigating SCZ-like behavior. The OM-MSC-exos have the capacity to modulate glial cell activation, diminish neuroinflammation, and promote BDNF-associated synaptic plasticity and neurogenesis, thus ameliorating SCZ-like behaviors. In summary, intranasal administration of OM-MSC-exos offers a multifaceted approach to address SCZ mechanisms, promising innovative treatments for this intricate disorder., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

A Cu/Pd-cocatalyzed 1,5-boroacylation of cyclopropyl-substituted ACPs with B 2 pin 2 and acid chlorides has been developed. Using cyclopropyl-substituted ACPs as the starting material, a broad range of 1,5-boroacylated products with multiple functional groups was prepared in good yields with excellent regio- and stereoselectively. Both aromatic and aliphatic acid chlorides were tolerated in this reaction.

Ulcerative colitis is an inflammatory bowel disease with increasing prevalence and incidence. Current treatments for ulcerative colitis are not generally applicative and are often accompanied by side effects. IGF2 is an endogenous protein that plays roles in anti-inflammation and stemness maintenance, but little is known about its mechanism and function in the progression of ulcerative colitis. In this study, mouse recombinant IGF2 was used in a mouse model of ulcerative colitis established by DSS. IGF2 expression was reduced in colon tissues but not plasma of DSS-induced colitis mice. IGF2R expression was also decreased in colitis colons, which was then elevated by recombinant IGF2. Recombinant IGF2 alleviated colon injury in colitis, which was evaluated by colon shortening, body weight loss and DAI score. IGF2 treatment also relieved the inflammatory response in colitis, which was assessed by the spleen weight index, MPO activity and proinflammatory cytokine expression and was also detected in LPS-stimulated RAW264.7 cells in vitro. Moreover, IGF2R was predicted and further verified to interact with the Sting protein, and the cGAS-Sting pathway as a key pathway for stemness regulation, was upregulated in colonic colons, which was blocked by IGF2 treatment. Additionally, IGF2 treatment can maintain colonic stemness and further repair colonic tight junction function in DSS-induced colitis. In conclusion, IGF2/IGF2R downregulated the cGAS-Sting pathway to sustain colonic stemness and barrier integrity to protect against ulcerative colitis induced by DSS., 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 © 2023 Elsevier B.V. All rights reserved.)

To investigate the influence of pelvic incidence (PI) on the kyphosis curve patterns and clinical outcomes in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis and to construct a classification of AS according to the PI value for surgical decision-making. 107 AS patients underwent single-level lumbar pedicle subtraction osteotomy (PSO) and finished a minimal of 2-year follow-up. All patients were divided into three groups: low PI (PI ≤ 40°), moderate PI (40° < PI ≤ 60°), and high PI (PI > 60°). Standing lateral radiographs were taken to evaluate the location of kyphotic apex, thoracic kyphosis (TK), lumbar lordosis (LL), C7 sagittal vertical axis (SVA), spino-sacral angle (SSA), global kyphosis (GK), PI, sacral slope (SS), and pelvic tilt (PT). Visual Analogue Scale (VAS) score, Oswestry Disability Index (ODI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were used to evaluate quality of life. Before surgery, a significant difference was shown in the average LL and the mean GK in high PI group was the largest among the three groups. Correction of SVA, GK and LL in high PI group was the smallest among the three group. No significant difference in clinical outcomes was found among the three groups before surgery and at the final follow-up. Regarding the preoperative sagittal profile, the kyphosis curve pattern of moderate PI group is similar to that of low PI group. For AS patients in these two groups, harmonious sagittal alignment can be restored by a single-level PSO. However, the sagittal imbalance is insufficiently realigned by a single-level PSO in a patient with high PI., 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 © 2023. Published by Elsevier Ltd.)

It is unclear who can benefit from tracheal intubation in the moderate (mTBI) traumatic brain injury (TBI) population. Given that mTBI patients are conscious, intubation can cause intense stress, possibly triggering neurological deterioration. Therefore, identifying potential risk factors for intubation in mTBI patients can serve as a valuable clinical warning. We sought to investigate whether elevated D-dimer is a possible risk factor for intubation in mTBI patients. Using the STROBE statement, adult patients with isolated TBI (Glasgow Coma Scale [GCS] score 9-13) treated at a high-volume neurotrauma center between January 2015 and December 2020 were reviewed. The demographics, clinical presentation, neuroimaging, and laboratory information were collected based on the patients' electronic medical record. D-dimer values were assessed from serum when patients were admitted to the hospital. The primary study end-point was that the mTBI patient was intubated within 72 h upon admission. A total of 557 patients with mTBI were finally included in this study. Of these, 85 (15.3%) patients were intubated. Multi-variate logistic regression analysis showed that high-level D-dimer (≥17.9mg/L) was significantly associated with early tracheal intubation in mTBI patients (odds ratio, 3.10 [1.16-8.25]; p  = 0.024) after adjusting for age, sex, GCS scores, Marshall scores, and Injury Severity Scores. Sensitivity analysis showed that high-level D-dimer had a robust correlation with intubation in the different subgroups or after propensity score matching. High-level D-dimer on admission is an independent risk factor for early tracheal intubation in isolated mTBI patients., Competing Interests: No competing financial interests exist., (© Qi Zhang et al., 2023; Published by Mary Ann Liebert, Inc.)

Chronic social isolation (SI) stress, which became more prevalent during the COVID-19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti-inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three-week-old male mice were randomly housed for 8 weeks in either group housing (GH) or SI. The animals were divided into normal saline-treated GH, normal saline-treated SI, and betaine-treated SI groups in the sixth week. The cognitive and depression-like behavior was determined in the eighth week. We found that long-term betaine administration improved cognitive behavior in SI mice but failed to prevent depression-like behavior. Moreover, long-term betaine administration inhibited hippocampal microglia over-activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic-pituitary-adrenal axis. Collectively, our findings reveal that betaine can improve SI-induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness., (© 2023 John Wiley & Sons, Ltd.)

The natural prenylated chalcone isobavachalcone (IBC) shows good antibacterial activity against Gram-positive bacteria but is ineffective against Gram-negative bacteria, most likely due to the outer membrane barrier of Gram-negative bacteria. The Trojan horse strategy has been shown to be an effective strategy to overcome the reduction in the permeability of the outer membrane of Gram-negative bacteria. In this study, eight different 3-hydroxy-pyridin-4(1H)-one-isobavachalcone conjugates were designed and synthesized based on the siderophore Trojan horse strategy. The conjugates exhibited 8- to 32-fold lower minimum inhibitory concentrations (MICs) and 32- to 177-fold lower half-inhibitory concentrations (IC 50 s) against Pseudomonas aeruginosa PAO1 as well as clinical multidrug-resistant (MDR) strains compared to the parent IBC under iron limitation. Further studies showed that the antibacterial activity of the conjugates was regulated by the bacterial iron uptake pathway under different iron concentration conditions. Studies on the antibacterial mechanism of conjugate 1b showed that it exerts antibacterial activity by disrupting cytoplasmic membrane integrity and inhibiting cell metabolism. Finally, conjugate 1b showed a lower cytotoxic effects on Vero cells than IBC and a positive therapeutic effect in the treatment of bacterial infections caused by Gram-negative bacteria PAO1. Overall, this work demonstrates that IBC can be delivered to Gram-negative bacteria when combined with 3-hydroxy-pyridin-4(1H)-ones as siderophores and provides a scientific basis for the development of effective antibacterial agents against Gram-negative bacteria., 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 © 2023 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the correlation of cognitive dysfunction with intracranial lesions and symptoms of depression and anxiety in patients with neuromyelitis optica spectrum disorders (NMOSD). Methods: Thirty-one NMOSD patients (7/24 males/females) were enrolled in the Department of Neurology of the Sixth Medical Center of the PLA General Hospital from August 2019 to August 2022. The average age was 42±13 years, and the average education level was 12 (9, 12) years. There were 30 healthy controls, 11/19 males/females, with an average age of 47±9 years and an average education of 12 (9, 15) years. The general clinical data and imaging data were collected, and the subjects were assessed on their cognition, anxiety and depression using the assessment scale approved at home and abroad. A cross-sectional study was conducted on them. The t -test or Wilcoxon test was used for inter-group comparison, and Pearson test or Spearman test was used to explore the correlation between the cognition of NMOSD patients and their intracranial lesions, depression and anxiety. Results: Compared with the healthy control group, NMOSD patients had significantly lower scores on MoCA ( Z =-3.10, P =0.002), CRAVLT-N7 ( Z =-5.12, P <0.001), CRAVLT-N8 ( t =-4.40, P <0.001), ROCF-R ( t =-3.10, P <0.01), ROCF-C ( Z =-2.72, P <0.01), PASAT-3 ( Z =-2.71, P <0.01), PASAT-2 ( Z =-3.14, P <0.01), and CWT-A ( Z =-3.10, P <0.01)scales. Frontal lobe lesions were negatively correlated with PASAT-2 ( r =-0.448, P =0.012) scores, temporal lobe lesions were negatively correlated with CRAVLT-N9 ( r =-0.564, P =0.001), and parietal lobe lesions were negatively correlated with MoCA ( r =-0.374, P =0.038), PASAT-3 ( r =-0.426, P =0.017), and PASAT-2 ( r =-0.459, P =0.009) scores; The scores of MoCA ( r =-0.392, P =0.029), CRAVLT-N6 ( r =-0.396, P =0.028), CRAVLT-N7 ( r =-0.415, P =0.020), CRAVLT-N8 ( r =-0.406, P =0.023), PASAT-3 ( r =-0.537, P =0.002) and PASAT-2 ( r =-0.495, P =0.005) scales were negatively correlated with the scores of HAMD assessment, and the scores of PASAT-3 ( r =-0.499, P =0.004) and PASAT-2 ( r =-0.452, P =0.011) were negatively correlated with the scores of HAMA. Conclusions: The cognitive function of patients with NMOSD is significantly reduced, involving multiple cognitive domains. The cognitive function is affected by the distribution of intracranial lesions and the degree of depression and anxiety.

Depression is one of the most common mental illnesses, affecting more than 350 million people worldwide. However, the occurrence of depression is a complex process involving genetic, physiological, psychological, and social factors, and the underlying mechanisms of its pathogenesis remain unclear. With advances in sequencing technology and epigenetic studies, increasing research evidence suggests that long noncoding RNAs (lncRNAs) play nonnegligible roles in the development of depression and may be involved in the pathogenesis of depression through multiple pathways, including regulating neurotrophic factors and other growth factors and affecting synaptic function. In addition, significant alterations in lncRNA expression profiles in peripheral blood and different brain regions of patients and model animals with depression suggest that lncRNAs may function as biomarkers for the differential diagnosis of depression and other psychiatric disorders and may also be potential therapeutic targets. In this paper, the biological functions of lncRNAs are briefly described, and the functional roles and abnormal expression of lncRNAs in the development, diagnosis and treatment of depression are reviewed., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: To investigate the remodeling morphology of subluxated osteotomy vertebra in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis after single-level closing-opening wedge osteotomy (COWO)., Materials and Methods: Standing lateral radiographs were taken to evaluate sagittal parameters including lumbar lordosis (LL), C7 sagittal vertical axis (SVA), global kyphosis (GK), sacral slope (SS), and pelvic tilt (PT). Radiographic parameters of the osteotomy vertebra included osteotomized vertebra angle (OVA), sagittal translation (ST), anterior height (AH), posterior height (PH), and middle height (MH) of the osteotomy vertebrae. Furthermore, lateral projection area of the vertebral body was also measured to evaluate the remodeling of the osteotomy vertebrae., Results: Sixty AS patients who underwent single-level lumbar COWO with a minimal 2-year follow-up were included. The cohort consisted of 54 males and 6 females with an average age of 36.6 years. All patients were divided into two groups according to the development of vertebral subluxation (VS): 15 in VS group (ST ≥ 5 mm), 45 in non-VS group (ST < 5 mm). There was significant difference in the correction of GK, SVA, and the loss of correction of SVA between AS patients with and without VS. Significant difference in vertebra-related parameters regarding AH and OVA was found between VS group and non-VS group (P < 0.05)., Conclusions: After COWO, new bone formation narrowing the gap and adaptive resorption of the anterior bony beak at the osteotomy level during follow-up was surprisingly favorable. However, the ability of spinal canal remodeling is limited in patients complicated with VS., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Evidence suggests that neurometabolite alterations may be involved in the pathophysiology of autism spectrum disorders (ASDs). We performed a meta-analysis of proton magnetic resonance spectroscopy ( 1 H-MRS) studies to examine the neurometabolite levels in the brains of patients with ASD. A systematic search of PubMed and Web of Science identified 54 studies for the meta-analysis. A random-effects meta-analysis demonstrated that compared with the healthy controls, patients with ASD had lower N-acetyl-aspartate-containing compound (NAA) and choline-containing compound (Cho) levels and NAA/(creatine-containing compound) Cr ratios in the gray matter and lower NAA and glutamate + glutamine (Glx) levels in the white matter. Furthermore, NAA and gamma-aminobutyric acid (GABA) levels, NAA/Cr ratios, and GABA/Cr ratios were significantly decreased in the frontal cortex of patients with ASD, whereas glutamate (Glu) levels were increased in the prefrontal cortex. Additionally, low NAA levels and GABA/Cr ratios in the temporal cortex, low NAA levels and NAA/Cr ratios in the parietal and dorsolateral prefrontal cortices, and low NAA levels in the cerebellum and occipital cortex were observed in patients with ASD. Meta-regression analysis revealed that age was positively associated with effect size in studies analyzing the levels of gray matter NAA and white matter Glx. Taken together, these results provide strong clinical evidence that neurometabolite alterations in specific brain regions are associated with ASD and age is a confounding factor for certain neurometabolite levels in patients with ASD., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To investigate the causes of ineffectiveness of platelet transfusion with monoclonal antibody solid phase platelet antibody test (MASPAT) matching in patients with allogeneic hematopoietic stem cell transplantation and explore the strategies of platelet transfusion., Methods: A case of donor-specific HLA antibodies (DSA) induced by transfusion which ultimately resulted in transplantation failure and ineffective platelet transfusion with MASPAT matching was selected, and the causes of ineffective platelet transfusion and platelet transfusion strategy were retrospectively analyzed., Results: The 32-year-old female patient was diagnosed as acute myeloid leukemia (high risk) in another hospital with the main symptoms of fever and leukopenia, who should be admitted for hematopoietic stem cell transplantation after remission by chemotherapy. In the course of chemotherapy, DSA was generated due to platelet transfusion, and had HLA gene loci incompatible with the donor of the first transplant, leading to the failure of the first transplant. The patient received platelet transfusion for several times before and after transplantation, and the results showed that the effective rate of MASPAT matched platelet transfusion was only 35.3%. Further analysis showed that the reason for the ineffective platelet transfusion was due to the missed detection of antibodies by MASPAT method. During the second hematopoietic stem cell transplantation, the DSA-negative donor was selected, and the matching platelets but ineffective transfusion during the primary transplantation were avoided. Finally, the patient was successfully transplanted and discharged from hospital., Conclusions: DSA can cause graft failure or render the graft ineffective. For the platelet transfusion of patients with DSA, the platelet transfusion strategy with matching type only using MASPAT method will miss the detection of antibodies, resulting in invalid platelet transfusion.

Background: The teaching mode of fitness exercise prescriptions for college students in physical education conforms to the scientific principles and rules of fitness, which can adapt to the characteristics of students' individual physiological functions and stimulate their interest in learning., Aim: To analyze the effect of prescribed exercise teaching on the sports quality and mental health of college students., Methods: The participants of the study were 240 students in our class of 2021, of which 142 were men and 98 were women. The 240 students were randomly divided into an experimental group using the exercise prescription teaching model and a control group using the conventional teaching model. The experimental and control groups were divided into four classes of 30 students each. The teaching activities of the two teaching mode groups were strictly controlled, and the same tests were used before and after the experiment to test the subjects' exercise quality (in-cluding standing long jump, 50 m race, 800 m race, sit-ups, sit-and-reach), physical form (including height, weight, Ketorolai index), cardiopulmonary function (including heart rate, blood pressure, spirometry, 12-min running distance, maximum oxygen intake) and mental health (SCL-90, including somatization, obsessive-compulsive, interpersonal, depression, anxiety, hostility, phobia, paranoia, psychotic symptoms) to understand the effects of the exercise prescription teaching mode on students' physical and mental health status., Results: There were differences in the exercise scores of standing long jump, 50 m, 800 m/1000 m running, sit-ups, and sit-and-reach in the experimental group after the experiment compared with those before the experiment, and the above indices of the experimental group were different from those of the control group after the experiment ( P < 0.05). There were differences in body weight and Ketorolai index in the experimental group after the experiment compared to those before the experiment, and the indices of the experimental group were also different from those of the control group after the experiment ( P < 0.05). After the experiment, there were differences in spirometry, 12-min running distance, and maximum oxygen intake in the experimental group compared to those before the experiment, and the indices of the experimental group were also different from those of the control group after the experiment ( P < 0.05). After the experiment, the indicators of somatization, interpersonal sensitivity, depression, anxiety, and hostility in the experimental group were different from those in the pre-experimental group, and the indexes of the experimental group were also different from those of the control group after the experiment ( P < 0.05)., Conclusion: Exercise prescription teaching can mobilize college students' consciousness, enthusiasm, and initiative; expand personalities; enhance physical fitness and improve their mental health more than the conventional fitness exercise prescription teaching method., Competing Interests: Conflict-of-interest statement: All authors disclosed no relevant relationships., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the histomorphological manifestations of hippocampal CA1 region and the expression of extracellular regulatory protein kinase (ERK), cyclic adenosine response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in chronic fatigue syndrome (CFS) rats, so as to explore the mechanisms of TEAS in improving the learning and memory abilities of CFS rats., Methods: Forty male Wistar rats were randomly divided into normal group (10 rats) and modeling group (30 rats); then after modeling, they were selected and randomly divided into model group (10 rats) and TEAS group (10 rats). CFS rats model was prepared by sleep deprivation combined with weight-bearing swimming. Rats in the TEAS group were stimulated with Han's acupoint nerve stimulator at bilateral "Zusanli" (ST36) and "Shenshu" (BL23) (2 Hz/15 Hz, 1-2 mA), 20 min each time, once a day for 4 weeks with 1 d rest every 6 d. The score of general conditions of rats was evaluated. The learning and memory ability was tested with Morris water maze. The morphology and ultrastructure of hippocampal CA1 region were observed by HE staining and transmission electron microscopy. The expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were detected by real time quantitative PCR and Western blot, respectively., Results: Compared with the normal group, the score of general condition was increased ( P <0.01); the escape latency was prolonged ( P <0.05, P <0.01) and the times of crossing the original platform was decreased ( P <0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were decreased ( P <0.05, P <0.01) in the model group. Compared with the model group, the scores of general condition on the 42 nd and 49 th day were decreased ( P <0.05, P <0.01); the escape latency was shortened ( P <0.01, P <0.05)and the times of crossing the original platform were increased ( P <0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were increased ( P <0.01, P <0.05) in the TEAS group. The morphology of neurons in hippocampal CA1 region was normal in the normal group. In the model group, the number of neurons in hippocampal CA1 region decreased, the arrangement of nerve cells was scattered, the number of apoptotic cells increased, some nuclear structures disappeared, nuclear heterochromatin increased, the cell membrane wrinkled, the chromatin appeared empty bright area, and the crista was incomplete. Compared with the model group, the nerve cells morphology in hippocampal CA1 region was more regular, the number of apoptotic cells decreased, the chromatin and the cytoplasm were uniformly distributed, and the crista was relatively intact in the TEAS group., Conclusion: TEAS can improve the learning and memory ability of CFS rats, the mechanisms may be related to improving the neural structure of hippocampal CA1 region and up-regulating the expression levels of ERK/CREB/BDNF.

Pseudomonas aeruginosa infections are often complicated by the fact that it can easily form a biofilm that increases its resistance to antibiotics. Consequently, the development of novel antibacterial agents against biofilm-associated drug-resistant P. aeruginosa is urgently needed. Herein, we report a series of 3-hydroxy-pyridin-4(1 H )-ones-ciprofloxacin conjugates that were designed and synthesized as dual antibacterial and antibiofilm agents against P. aeruginosa . A potential 2-substituted 3-hydroxy-1,6-dimethylpyridin-4(1 H )-one-ciprofloxacin conjugate ( 5e ) was identified and had the best minimum inhibitory concentrations of 0.86 and 0.43 μM against P. aeruginosa 27853 and PAO1 and reduced 78.3% of biofilm formation. In addition, 5e eradicates mature biofilms and kills living bacterial cells that are incorporated into the biofilm. Studies on the antibiofilm mechanism of conjugates showed that 5e interferes with iron uptake by bacteria, inhibits their motility, and reduces the production of virulence. These results demonstrate that 3-hydroxy-pyridin-4(1 H )-ones-ciprofloxacin conjugates are potent in the treatment of biofilm-associated drug-resistant P. aeruginosa infections.

Objective: Anti-Ro60 and anti-Ro52 antibodies are associated with different connective tissue diseases (CTDs). However, the clinical significance of anti-Ro antibodies is not always consistent among different global regions. The aim of this study was to investigate the clinical characteristics of patients with anti-Ro antibodies., Methods: A total of 1596 inpatients with anti-Ro antibodies were included in the study. Demographic, clinical, and serological data were compared between individuals with different profiles of anti-Ro antibodies: patients with anti-Ro52 antibodies alone, patients with anti-Ro60 antibodies alone, and patients with combined anti-Ro52 and anti-Ro60 antibodies., Results: Of the 1596 patients, 1362 (85.3%) were female, the mean age was 45.5 years, and systemic lupus erythematosus (SLE) (46.0%) and Sjogren's syndrome (SS) (19.0%) were the most common CTD diagnoses. Among the patients with anti-Ro52 antibodies alone, idiopathic inflammatory myopathy (18.8%) and SLE (17.6%) were the most common CTD diagnoses. The coexistent autoantibodies of this group were significantly lower compared with those of the other two groups, while the presence of anti-Jo1 antibodies were significantly higher compared with those of the other two groups (3.7% vs. 0.6% vs. 1.9%, p = 0.029). In addition, the patients with isolated anti-Ro52 antibodies were more likely to suffer from interstitial lung disease (35.5% vs. 11.3% vs. 13.7%, p < 10 -4 ) and pulmonary arterial hypertension (10.1% vs. 5.3% vs. 3.6%, p = 0.001) compared with the other two groups of patients. Compared with patients with isolated anti-Ro52 or anti-Ro60 antibodies, the patients with combined anti-Ro52 and anti-Ro60 antibodies were more likely to suffer from xerophthalmia and xerostomia. Furthermore, hypocomplementemia, hyperglobulinemia, and proteinuria were particularly prevalent in patients with anti-Ro60 antibodies., Conclusion: Different profiles of anti-Ro antibodies were significantly associated with clinical phenotypic features in CTDs, indicating the potential diagnostic and prognostic value of these antibodies in clinical practice., Competing Interests: The authors have declared that they have no competing interests., (Copyright © 2023 Hai-Tao Yang et al.)

Background: Recent genetic research identified a protective factor against late-onset Alzheimer's disease (AD) in Caucasians, a variant called rs3747742-C in the TREML2 gene. However, the roles of other TREML2 variants in AD have not been fully explored., Objective: We conducted a focused analysis of 16 TREML2 variants, examining their connection to AD by studying their correlation with cerebrospinal fluid (CSF) proteins, neuroimage, and cognition in the Alzheimer's Disease Neuroimaging Initiative database (ADNI)., Methods: A multiple linear regression model was utilized to estimate potential associations between TREML2 genotypes and various endophenotypes in the entire ADNI sample at baseline, with age, gender, years of education, and APOE ɛ4 status included as covariates. To examine changes in clinical outcomes over time, linear mixed-effects models were employed., Results: We found that the SNP rs17328707-A was associated with higher ADNI-VS scores, smaller ventricles, and larger middle temporal volume at baseline. The SNP rs6915083-G was linked to lower CSF t-tau and p-tau levels, and higher CSF Aβ levels. The SNP rs9394766-G was associated with a smaller hippocampus and larger ventricles at baseline. In longitudinal cohorts, the rs6915083-G SNP was associated with changes in ADNI-MEM and ADNI-EF scores, as well as the rate of hippocampal and middle temporal atrophy., Conclusion: Our findings reveal that TREML2 gene variants have different effects on AD. Two variants are protective, while one may be a risk factor. This enhances our understanding of AD genetics and could guide future research and personalized treatments.

Understanding the principle of regulated cell death (RCD) such as ferroptosis and apoptosis provides opportunities to overcome sorafenib resistance of HCC. Complexin II (CPLX2) is involved in calcium-dependent fusion of vesicles and plasma membrane, and recent studies showed CPLX2 is involved in cancer progression. However, the expression and function of CPLX2 are unclear in hepatocellular carcinoma (HCC). qPCR and western blotting assays were used to detect the levels of CPLX2. MTT and colony formation assays were used to detect cell viability. The contents of iron, ROS, MDA, and GSH were used to evaluate the function of CPLX2 on ferroptosis, while the flow cytometry and TUNEL assays were used to evaluate the role of CPLX2 on apoptosis. Our analysis showed CPLX2 is significantly upregulated in HCC, which predicts poor overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), and disease-specific survival (DSS) for patients with HCC. Further function enrichment analysis of genes related to CPLX2 showed CPLX2 is involved in the NRF2 pathway. Downregulation of CPLX2 can inhibit NRF2 expression and the transcription of its downstream genes, which confirms that CPLX2 is involved in NRF2 pathway. Cell viability assay showed that ferroptosis and apoptosis inhibitors can reverse the inhibition effect of CPLX2-knockdown on cell survival, respectively. And downregulation of CPLX2 significantly promotes the contents of iron, ROS, and MDA, while inhibiting the GSH level of HCC cell lysate, suggesting CPLX2 involved in ferroptosis. Moreover, downregulation of CPLX2 promotes the apoptosis of HCC cells by flow cytometry and TUNEL assay. And upregulation of NRF2 can partly reverse the inhibitory effect of CPLX2-downregulation on ferroptosis and apoptosis. Finally, we found downregulation of CPLX2 aggravates cell death induced by sorafenib. CPXL2 regulates ferroptosis and apoptosis through NRF2 pathway, and CPLX2 knockdown promotes cell death induced by sorafenib. CPLX2 might be an effective target for therapy patients with HCC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Herpes simplex virus (HSV), an alphaherpesvirus, is highly prevalent in the human population and is known to cause oral and genital herpes and various complications. Represented by acyclovir (ACV), nucleoside analogs have been the main clinical treatment against HSV infection thus far. However, due to prolonged and excessive use, HSV has developed ACV-resistant strains. Therefore, effective treatment against ACV-resistant HSV strains is urgently needed. In this review, we summarized the plant extracts and natural compounds that inhibited ACV-resistant HSV infection and their mechanism of action., 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 Xu, Zhong, Xi, Li and Xu.)

Neuroinflammation plays a key role in the development of depression-like behaviors.Endoplasmic reticulum (ER) stress,defined as accumulation of unfolded proteins in the ER,is suggested tocollaboratewithinflammation process to drive sustained neuroinflammation. Protein kinase R-like endoplasmic reticulum kinase (PERK) is ofparticularly attractive target because it plays key rolein the regulation of ER stress-induced neuroinflammation, however, little isknown whether PERKmediatedER stress is implicated in LPS-induced depression-like behaviors.Thus, we aimed to evaluate the induction of PERK pathwayin mice with depression-like behaviors induced by LPS, as well as the alterations in depression-like behaviorsfollowing the blocking of PERK pathway.We found that LPS challenges resulted in enhanced PERK in the hippocampus, with no alteration in the prefrontal cortex. Importantly, we found that PERKinhibitorISRIB reducedthe proinflammatory responsesof microglia in the context of acute LPS-induced brain inflammation, and subsequent the preserved hippocampal neurogenesis, and improvement in depression-like behavioroutcomes following LPS challenges.It was also worth mentioning thatISRIB treatmentreduced the peripheral pro-inflammatory cytokines includingIL-1β, IL-6 and IL-18. Thus, targetingPERK mediated Endoplasmic reticulum stress may be a promising antidepressant and anti-inflammatory candidate drug for the alleviation of neuroinflammationmediated depression, and PERKinhibitorISRIBmay havebenefits for combating major depressive disorder., 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 © 2022 Elsevier B.V. All rights reserved.)

Objective: A dynamic gel loaded with lyophilized platelet-rich plasma-chitosan/difunctionalized polyethylene glycol (LPRP-CP) was prepared to investigate its hemostatic antibacterial and promoting wound healing of scald wounds through in vitro and in vivo experiments., Methods: In this study, normal gauze/blank tablet (Ctrl), LPRP-CP, Chitosan HUCHUANG Powder(Chito P)and ChitoGauze XP PRO group (Chito G group) were set. The hemostatic effect and promoting healing effect of the four groups of materials were evaluated by establishing rabbit ear artery hemorrhage model and superficial Ⅱ° scalded model of skin on the back. The hemostatic time and bleeding amount were calculated and the gross and histological results of scald healing were observed. The antibacterial effect of the four groups of materials was evaluated by antibacterial test in vitro., Results: In the rabbit ear arterial hemorrhage model, the hemostasis of all materials was successful. The hemostatic time of Ctrl, Chito P, LPRP-CP and Chito G groups was 213.33±38.30, 118.33±24.01, 115.00±8.37 and 111.67±11.69 s, respectively. The blood loss was 1233.83±992.27, 346.67±176.00, 193.33±121.47 and 147.50±80.66 mg, respectively. Compared with Ctrl, the hemostasis time of LPRP-CP, Chito P and Chito G group was significantly shorter (P<0.001), and the amount of blood loss of LPRP-CP and Chito G group was decreased (P<0.05). Compared with LPRP-CP, there were no significant differences in hemostatic time and blood loss between Chito P and Chito G group (P>0.05). In the model of superficial Ⅱ° scalded on the back of rabbit, the wound healing rate of LPRP-CP was faster than that of the other three groups at the same time, and the healing effect was perfect. In the antibacterial test in vitro, only LPRP-CP had better anti-S. aureus effect, and all groups had no anti-E. coli effect., Conclusion: LPRP-CP is an excellent hemostatic material for superficial wounds, and has certain antibacterial and wound healing effects, which has a wide academic value and research prospects.

Objective: To establish a new method for synthesizing Lewis blood group antigens, that is, the mimotopes of Lewis blood group antigens were screened by using an alpaca phage display nanobody library., Methods: We selected mimotopes of the Lewis a (le a ) antigen by affinity panning of an alpaca phage display nanobody library using a monoclonal anti-le a antibody. Enzyme-linked immunosorbent assay (ELISA) was used to test the affinity of the positive clones for the monoclonal anti-le a antibody, and the high-affinity positive clones were selected for sequencing and synthesis. Finally, the sensitivity, specificity and reactivity of the synthesized le a mimotope in clinical samples were verified by ELISA., Results: A total of 96 phage clones were randomly selected, and 24 were positive. Fourteen positive clones with the highest affinity were selected for sequencing. The result showed that there were 5 different sequences, among which 3 sequences with the highest frequency, largest difference and highest affinity were selected for expression and synthesis. The sensitivity and specificity of le a mimic antigen by ELISA showed that, the minimum detection limit of gel microcolumn assay (GMA) and ELISA method were 25 times different, and the le a mimic antigen had no cross reacted with the other five unrelated monoclonal antibodies(P<0.001). Finally, 30 clinical plasma samples were analyzed. The mean absorbance of the 15 positive plasma samples was significantly higher than that of the 15 negative plasma samples (P=0.02). However, the positive signal values of the clinical samples were much lower than those of the monoclonal antibodies., Conclusion: A new method of screening le a mimic antigen by using alpaca phage nanoantibody library has been established, which is expected to realize the screening of le a mimotopes, thus realizing the application of high-sensitivity detection methods such as ELISA and chemiluminescence in blood group antibody identification.

Objective: To investigate the relationship between nutritional risk status and clinical outcome in children with tuberculous meningitis (TBM). Methods: The clinical data (basic information, clinical symptoms and laboratory test results) of 112 patients with TBM, who were admitted to Department of Pediatric Infectious Diseases of West China Second Hospital of Sichuan University,from January 2013 to December 2020 were retrospectively analyzed. The patients were divided into the nutritional risk group and the non-nutritional risk group according to the assessment of the nutritional risk by the STRONGkids Scale. The variables of basic information, clinical symptoms and laboratory test measurements etc. were compared between the two groups by using Student t test, Rank sum test or Chi-square test. Multivariate Logistic regression analysis were used to analyze nutritional risk factors. Results: Among 112 patient with TBM, 55 were males and 57 females. There were 62 cases in the nutritional risk group and 50 cases in the non-nutritional risk group. The proportion of cases with nutritional risk was 55.4% (62/112). Patients in the nutritional risk who lived in rural areas, had symptoms of brain nerve damage, convulsions, emaciation and anorexia, with a diagnosis time of ≥21 days, and the level of cerebrospinal fluid (CSF) protein were all higher than those in the non-nutritional risk group ((50 cases (80.6%) vs . 32 cases (64.0%), 20 cases (32.3%) vs .8 cases (16.0%), 33 cases (53.2%) vs . 15 cases (30.0%), 30 cases (48.4%) vs . 2 cases (4.0%), 59 cases (95.2%) vs . 1 case (2.0%),41 cases (66.1%) vs .18 cases (36.0%), 1 406 (1 079, 2 068) vs . 929 (683, 1 208) mg/L, χ 2 =3.91, 3.90, 6.10, 26.72, 98.58, 10.08, Z =4.35, all P <0.05). The levels of serum albumin,hemoglobin,lymphocyte count, white blood cell count, and CSF glucose were significantly lower in patients with nutritional risk ((36±5) vs . (41±4) g/L, (110±17) vs . (122±14) g/L, 1.4 (1.0, 2.0) vs . 2.3 (1.6, 3.8)×10 9 /L, 7.8 (6.3, 10.0)×10 9 vs . 10.0 (8.3, 12.8)×10 9 /L, 1.0 (0.8, 1.6) vs . 2.1 (1.3, 2.5) mmol/L, t =-6.15, -4.22, Z =-4.86, -3.92, -4.16, all P <0.05).Increased levels of serum albumin ( OR =0.812, 95% CI :0.705-0.935, P =0.004) and lymphocyte count ( OR =0.609, 95% CI :0.383-0.970, P =0.037) may reduce the nutritional risk of children with TBM; while convulsions ( OR =3.853, 95% CI :1.116-13.308, P =0.033) and increased level of CSF protein ( OR =1.001,95% CI :1.000-1.002, P =0.015) may increase the nutritional risk of children with TBM. Similarly, the rate of complications and drug-induced liver injury was higher in the nutritional risk group (47 cases (75.8%) vs . 15 cases(30.0%), 31 cases (50.0%) vs .8 cases (16.0%), χ 2 =23.50, 14.10, all P <0.05). Moreover, the length of hospital stay was also longer in the nutritional risk group ((27±13) vs . (18±7) d, t =4.38, P <0.05). Conclusions: Children with TBM have a high incidence of nutritional risk. Convulsive, the level of serum albumin, the level of lymphocyte count and CSF protein may affect the nutritional risk of children with TBM. The nutritional risk group has a high incidence of complications and heavy economic burden.It is necessary to carry out nutritional screening and nutritional support for children with TBM as early as possible.

Background: The study aimed to evaluate the influence of thoracolumbar kyphosis secondary to ankylosing spondylitis (AS) on parameters of S2AI trajectory and to compare the ideal S2AI trajectory with those of the non-deformity patients with AS, sagittal deformity patients without AS, and the normal population reported in literatures., Methods: Sagittal parameters including global kyphosis (GK), pelvic tilt (PT) and sacral slope (SS) were measured. Besides, according to the simulated ideal S2AI trajectory on the CT images, trajectory parameters were measured including Sag angle, Tsv angle, Max-length, Sacral distance and Iliac width. Starting-point parameters were also measured including PSIS distance, Skin distance, Iliac wing and S2 midline., Results: Ninety-four AS-related thoracolumbar kyphosis patients were included. After adjusting the age and gender, twenty non-deformity patients with AS and 20 sagittal deformity patients without AS were selected to compare with patients with AS-related thoracolumbar kyphosis, respectively. Sag angle in deformity patients with AS was smaller than other two groups (P < 0.001). No difference was found in Tsv angle and Sacral distance between AS patients with and without deformity. However, these two parameters were shown significant differences between deformity patients with AS and without AS. In deformity patients with AS, no significant differences were found in all parameters between genders Furthermore, there were strong correlations between PT and the bilateral Sag angle (P < 0.001)., Conclusions: The thoracolumbar kyphosis secondary to AS affects the Sag angle of the ideal S2AI trajectory which was approximately 20° smaller than that in non-deformity patients with AS, sagittal deformity patients without AS, and the normal population. Additionally, the Tsv angle and the Sacral distance in AS patients with thoracolumbar kyphosis were about 10° and 10 mm larger than those in sagittal deformity patients without AS, and the normal population reported in literatures., (© 2022. The Author(s).)

Psychotic symptoms of dementia are highly prevalent and lead to poor medical outcomes and substantial dysfunction. To date, which drug to use remains controversial without a summary of all direct or indirect comparisons of pharmacotherapy. Therefore, we conducted a systematic review with pairwise and network meta-analysis to examine efficacy and tolerability outcomes of pharmacological treatments in dementia patients. MEDLINE, Cochrane Library, EMBASE, and PubMed were searched systematically up to August 31, 2020. We included trials of cholinesterase inhibitors (ChEIs), memantine, antipsychotics, antidepressants, and mood stabilizers, with final approval from the U.S. Food and Drug Administration. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities. This analysis is based on 34 trials, which included 10,415 patients randomly assigned to 15 commonly used drug regimens. Donepezil (standardized mean difference [SMD] -0.30, 95% credible interval [CrI] -0.50 to -0.12; SUCRA, 0.85), memantine (SMD -0.20, 95%CrI -0.34 to -0.07; SUCRA, 0.68) and aripiprazole (SMD -0.17, 95% CrI -0.32 to -0.02; SUCRA, 0.62) showed greater benefit than placebo, and with relatively good tolerability in network meta-analyses. Risperidone was also found to be more efficacious than placebo (SMD -0.16, 95% CrI -0.28 to -0.05; SUCRA, 0.60), but with poor tolerability (odds ratios [OR] 1.50, 95% CrI 1.06-2.26). Donepezil, memantine, haloperidol, aripiprazole and risperidone were more efficacious than quetiapine (SMDs ranged from -0.36 to -0.22). Besides, donepezil, memantine and mirtazapine were more efficacious than sertraline (SMDs ranged from -0.47 to -0.36). Most of the results were rated as "low" to "very low". Several effective treatment choices for psychotic symptoms are available across drug classes. Donepezil, memantine and aripiprazole are probably the appropriate options to consider when a pharmacological treatment is indicated. Given the limitations of the meta-analytic approach and the low methodological quality of the majority of studies, our results should be cautiously interpreted., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The position of Xuehai (SP10) is clear, but its locating method is vague, resulting in the disunity of clinical application and even possibly affecting the curative effect. Also, when learning the meridians and acupoints, the beginners are often confused by this issue possibly due to: ① when the bone-length proportional measurement combined with anatomic symbol (combination method) was adopted, it is not clear that the patient should take a posture of knee extension or knee flexion; ② when the combination method used, it is difficult to find the highest point of muscle eminence in the case of patient with thin vastus medialis muscle and fuzzy body surface projection; ③the simple method for locating SP10 is widely used at present, can it replace the combination method to locate this acupoint accurately？Guided by these questions, we, in the present paper, reviewed the rela-ted textbooks, works and other literature to explore the standard position of SP10, and the standard and simple methods for locating this acupoint. Comprehending various opinions, we hold that SP10 should be positioned under the extended knee posture, then, the acupoint's horizontal ordinate "2 cun superior to the medial end of the base of the patella" is determined by using bone-length proportional measurement to measure 2 cun from the bottom to the tip of the patella. Then, the body surface anatomic symbol method is used, when, the patient is asked to stretch the leg and contract the vastus medialis muscle, the highest spot of muscular eminence is the SP10. If the patient's muscular protuberance is not obvious, the middle line between the medial and lateral margins of the vastus medialis muscle is used as the vertical ordinate, and its intersection with the abscissa is SP10. The simple method is easy in operation and has a reference value, but may frequently produce errors, hence, it is not a substitution for the combination method.

The transformation of unstable austenite to ferrite or α′ martensite as a result of exposure to Xe+ or Ga+ ions at room temperature was studied in a 304 stainless steel casting alloy. Controlled Xe+ and Ga+ ion beam exposures of the 304 were carried out at a variety of beam/sample geometries. It was found that both Ga+ and Xe+ ion irradiation resulted in the transformation of the austenite to either ferrite or α′ martensite. In this paper, we will refer to the transformation product as a BCC phase. The crystallographic orientation of the transformed area was controlled by the orientation of the austenite grain and was consistent with either the Nishiyama–Wasserman or the Kurdjumov–Sachs orientation relationships. On the basis of the Xe+ and Ga+ ion beam exposures, the transformation is not controlled by the chemical stabilization of the BCC phase by the ion species, but is a result of the disorder caused by the ion-induced recoil motion and subsequent return of the disordered region to a more energetically favorable phase.

High entropy (HE) materials have received significant attention in recent years, due to their intrinsically high levels of configurational entropy. While there has been significant work exploring HE alloys and oxides, new families of HE materials are still being revealed. In this work we present the synthesis of a novel family of HE materials based on lanthanide oxysulfides. Here, we implement lanthanide dithiocarbamates as versatile precursors that can be mixed at the molecular scale prior to thermolysis in order to produce the high entropy oxysulfide. The target of our synthesis is the HE Ln 2 SO 2 phase, where Ln = Pr, Nd, Gd, Dy, Er and where Ln = Pr, Nd, Gd, Dy for 5 and 4 lanthanide samples, respectively. We confirmed the structure of samples produced by powder X-ray diffraction, electron microscopy, and high-resolution energy dispersive X-ray spectroscopy. Optical spectroscopy shows a broad emission feature centered around 450 nm as well as a peak in absorption at around 280 nm. From this data we calculate the band gap and Urbach energies of the materials produced.

Heterotopic ossification (HO) is frequently seen in patients with spinal injuries. Therefore, this study aimed to characterize the association of HO with ankylosing spondylitis (AS) through gene expression profiling. The human transcriptomic datasets (GSE73754 and GSE94683) were obtained from the Gene Expression Omnibus database for analysis. Overlapping differentially expressed genes (DEGs) were identified between AS and HO disease states. Subsequently, weighted gene co-expression network analysis (WGCNA) was performed for constructing and identifying hub genes for each condition. Finally, a consensus of the overlapping DEGs and the hub genes in AS and HO was taken for determining the key genes involved in AS-induced HO. Quantitative real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels in mesenchymal stem cells of AS patients and controls. Additionally, immunohistochemistry was performed on interspinous ligament samples for experimental validation of genes. DEG analysis identified 355 overlapping genes between HO and AS. WGCNA indicated that the salmon module of the 22 modules constructed, was most significantly correlated with AS-induced HO. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the salmon module indicated the presence of genes enriched in proteasome regulatory particle and proteasome pathways. mRNA expression analysis identified TCP1 and PSMC1 as the key genes in AS-induced HO. Further validation of these genes could help elucidate their role in the complex association of AS and HO.

Background: Many studies have indicated that autophagy plays an important role in multiple cancers, including hepatocellular carcinoma (HCC). This study aimed to establish a prognostic signature for HCC based on autophagy-related genes (ARGs) to predict the prognosis of patients., Methods: The list of ARGs was derived from screening National Center for Biotechnology Information (NCBI)-Gene and Molecular Signatures Database (MSigDB) datasets. Differential analysis was conducted via the R limma package in HCC patients based on The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analysis were conducted to identify key prognostic ARGs via the survival package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by clusterProfiler package. The Estimation of Stromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm was used to conduct immune analysis. Finally, the correlation between the prognostic model and clinical characteristics was also assessed, including age, tumor-node-metastasis (TNM) stages, and tumor grades., Results: Firstly, 106 differential ARGs were identified and 10 candidates were further confirmed via Cox regression analysis, including BAMBI , HIF1A , SERPINE1 , EZH2 , SLC9A3R1 , IGFBP3 , HSPB8 , DAB2 , CXCL1 and PRNP . The receiver operating characteristic (ROC) curve analysis revealed that the ARGs risk model had a well diagnostic positive rate with 1-year area under the curve (AUC) =0.688 and 3-year AUC =0.674. Correlation analysis indicated that only advanced tumor stages were positively associated with high ARGs scores with P=0.0227. There were also significant differences in tumor purity (P=6.71e-05), infiltrating cell analysis (P=7.77e-05), immune analysis (P=7.9e-05), and stromal cells analysis (P=0.0015) in high- and low-risk ARGs samples. The genes HIF1A , IGFBP3 , and DAB2 were found to have high frequent missense mutations in samples with high-risk ARGs scores. Lastly, we also established a nomogram to predict overall survival (OS) of HCC by integrating ARGs scores and other clinical parameters., Conclusions: Our study established an autophagy-related signature for predicting the prognosis of HCC patients, providing a thorough understanding of the underlying mechanisms of autophagy in HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-21-664). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Objective: The objective of this study was to investigate the impact of the lumbar sagittal profile on pelvic orientation and pelvic motion during postural changes in patients with ankylosing spondylitis (AS) and thoracolumbar kyphosis and to evaluate the potential risk of prosthetic dislocation after total hip arthroplasty (THA) following pedicle subtraction osteotomy (PSO)., Methods: Seventy-two patients with AS-related thoracolumbar kyphosis following spinal osteotomy were retrospectively reviewed, and 21 healthy volunteers were recruited as a control group. Pre- and postoperative 2D full-body images in standing and sitting positions were obtained to evaluate the anterior pelvic plane angle (APPA), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), proximal femur angle (PFA), and femoroacetabular flexion during postural changes. Patients with AS were categorized in either a lordotic or kyphotic group based on the lumbar sagittal profile., Results: Significant increases in the SS and decreases in the APPA, PT, and LL were observed postoperatively in both the standing and sitting positions (p < 0.001 for all). Significantly higher APPA, PT, LL, and ΔPT, and lower SS, ΔSS, and ΔSS+ΔPFA were observed in the kyphotic group (p < 0.05). After undergoing PSO, ΔPT and ΔSS significantly decreased while femoroacetabular flexion significantly increased in both AS groups (p < 0.05), and no significant difference was present between the two groups (p > 0.05). Bath Ankylosing Spondylitis Radiology Hip Index scores in the kyphotic group were significantly worse than those in the lordotic group pre- and postoperatively (p < 0.05). No significant difference in parameters concerning pelvic motion (ΔAPPA, ΔPT, and ΔSS) was found when PSO was performed in the thoracolumbar or lumbar spine., Conclusions: Lumbar sagittal profiles greatly affect pelvic orientation and pelvic motion in AS. When THA is performed before PSO, AS patients with lumbar kyphosis are at higher risk of anterior prosthetic dislocation, while those with lordotic lumbar sagittal profiles are at higher risk of posterior dislocation. PSO should be performed prior to THA. After PSO, further decreased pelvic motion indicated a potential risk of posterior prosthetic dislocation after sequential THA, whereas theoretically patients with preoperative lumbar kyphosis are at higher risk of THA dislocation. The site where PSO was performed (thoracolumbar or lumbar spine) does not influence the risk of THA dislocation.

The clinical data of 47 patients [41 males, 6 females, aged (62±7) years] treated at the Department of Neurology of the Sixth Medical Center of PLA General Hospital from October 2018 to October 2020 who were diagnosed with severe bilateral vertebral artery stenosis/occlusion through Digital Subtraction Angiography (DSA) were retrospectively collected, and the characteristics of the compensatory pathways of collateral circulation were determined. Results showed that there were 8 intracranial and extracranial compensatory pathways, with posterior communicating artery as the major type (21 cases) for intracranial ones and deep carotid artery as the major type (16 cases) for extracranial ones. As the establishment of the compensatory pathway is closely related to the lesion site, DSA assessment for patients with severe bilateral vertebral artery stenosis/occlusion is helpful for clinicians to make judgement on prognosis of patients and choose individualized treatment plans.

Objective: To investigate the collateral circulation compensation model in patients with favorable prognosis of basilar artery occlusion/severe stenosis treated with drugs or endovascular therapy. Methods: Clinical data of patients with basilar artery occlusion/severe stenosis and good clinical outcome were retrospectively collected in the Department of Neurology, Sixth Medical Center of PLA General Hospital from January 2019 to January 2020. They were divided into intensive drug therapy group and combined endovascular therapy group. The number and ways of collateral compensation pathway described by digital substraction angiography (DSA) were analyzed, and the characteristics of the collateral compensation model were summarized. SPSS22.0 software was used for statistical analysis, and the constituent ratio (%) was used for statistical description of the enumeration data. Results: A total of 32 eligible patients were included, including 27 males and 5 females, with an average age 45-76 (59±10) years. The compensation model included posterior communicating artery-posterior cerebral artery (13 cases, 40.6%), posterior communicating artery-posterior cerebral artery-basilar artery (10 cases, 31.2%), cerebellar artery-anastomotic branches of superior cerebellar artery (8 cases, 25.0%), anterior choroid artery-anastomotic branches of posterior choroid artery (2 cases, 6.2%), collateral circulation not established (11 cases, 34.4%).In drug treatment group, collateral compensation was found in the majority (14/15), with mainly posterior communicating artery (10/14).Most patients in combined treatment group did not develop collateral compensation (10/17), anastomotic branches of PICA-SCA were the main routes (6/7). Conclusion: In patients with basilar artery occlusion/severe stenosis, favorable clinical outcome can be achieved in both groups of patients treated with intensive drug therapy or endovascular therapy.

Over the past few decades, the landscape of inorganic medicinal chemistry has been dominated by investigations on platinum or ruthenium, while the research based on other metal centers such as rhodium has been relatively insufficient. In this work, a series of cyclometalated rhodium(iii) complexes with imidazo[4,5-f][1,10]phenanthroline containing different aromatic rings were synthesized and characterized. Notably, all the complexes displayed stronger anticancer activity against various cancer cells compared with cisplatin. A mechanism study revealed that the rhodium complexes accumulated in the mitochondria, elevated the levels of mitochondrial reactive oxygen species (ROS) and released cytochrome c, indicating severe mitochondrial damage during the anticancer activity. Further studies illustrated that the rhodium complexes caused cell cycle arrest at the G2/M phase, upregulated the expression of p53 and reduced the ratio of B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated x (Bax), which ultimately resulted in cellular apoptosis. Overall, through mitochondrial pathways, these Rh(iii) complexes could induce cellular apoptosis to a larger extent than cisplatin and should be paid close attention as promising chemotherapeutic drugs in anticancer research.

Forests play an important role in regulating climate change and maintaining carbon balance. To explore the carbon storage and carbon sequestration rate of national forest parks is of great significance for carbon sequestration capacity assessment and sustainable forest management. A process-based ecosystem model (CEVSA2 model) was used to simulate the spatial distribution of carbon density, carbon storage and carbon sequestration rate of 881 national forest parks in China during 1982-2017. The results showed that the average carbon density of national forest parks was 255.18 t C·hm -2 , being higher than the average carbon density of forest ecosystem in China. In 2017, the total carbon storage of national forest parks increased to 3.56 Pg C, accounting for 11.0%-12.2% of the total carbon storage in national forest ecosystems. During 1982-2017, the average carbon sequestration rate of national forest parks reached 0.45 t C·hm -2 ·a -1 , and the carbon sequestration rate of all national forest parks was above 0.30 t C·hm -2 ·a -1 . National forest parks in the northeast and southwest of China had the highest total carbon storage. The national forest parks in northeast of China had the highest soil organic carbon sequestration rate, while those in eastern China and central southern China had the highest biomass carbon sequestration rate. The area of national forest parks accounted for 5.8% of the total forest area of China, playing an important role in forest carbon sink management of China. Accurate assessment of the growth status, carbon sequestration potential and carbon absorption characteristics of national forest parks could provide reference for the comprehensive assessment of ecosystem service of forest parks in China.

Background: The neutrophil-to-lymphocyte ratio (NLR) has emerged as an inflammatory marker. However, the associations of NLR with intracranial artery stenosis (ICAS) and ischemic stroke remain unclear. This study aimed to examine the associations of NLR with ICAS and ischemic stroke among a large and high-risk population., Methods: Participants with records of clinical characteristics were prospectively recruited from the Neurology Department and Health & Physical Examination Center of Qingdao Municipal Hospital. Logistic regression analysis was used to examine the associations of NLR with ICAS and ischemic stroke. Moreover, we also conducted parametric mediation analysis to estimate the effect of NLR on the risk of ischemic stroke mediated through ICAS., Results: A total of 2989 participants were enrolled in this study. After adjusting for covariates, NLR (OR = 1.125, 95%CI 1.070-1.183) and ICAS (OR = 1.638, 95%CI 1.364-1.967) were significantly associated with ischemic stroke. Compared with the first quartile NLR, the second, third and fourth quartiles NLR were independent risk predictors for ischemic stroke (P for trend < 0.001); the third and fourth quartiles were independent predictors for ICAS (P for trend < 0.001). The mediation analysis showed that ICAS partially mediated the association between NLR and ischemic stroke, accounting for 14.4% of the total effect (P < 0.001)., Conclusions: NLR was significantly associated with ICAS and ischemic stroke. Besides, ICAS partially mediated the association between NLR and ischemic stroke.

We report a simple, economical and low temperature route for phase-pure synthesis of two distinct phases of Cu-Sb-S, chalcostibite (CuSbS 2 ) and tetrahedrite (Cu 12 Sb 4 S 13 ) nanostructures. Both compounds were prepared by the decomposition of a mixture of bis(O-ethylxanthato)copper(II) and tris(O-ethylxanthato)antimony(III), without the use of solvent or capping ligands. By tuning the molar ratio of copper and antimony xanthates, single-phases of either chalcostibite or tetrahedrite were obtained. The tetrahedrite phase exists in a cubic structure, where the Cu and Sb atoms are present in different coordination environments, and tuning of band gap  energy was investigated by the incorporation of multivalent cationic dopants, i.e. by the formation of Zn-doped tetrahedrites Cu 12-x Zn x Sb 4 S 13 (x = 0.25, 0.5, 0.75, 1, 1.2 and 1.5) and the Bi-doped tetrahedrites Cu 12 Sb 4-x Bi x S 13 (x = 0.08, 0.15, 0.25, 0.32, 0.4 and 0.5). Powder  X-ray diffraction (p-XRD) confirms single-phase of cubic tetrahedrite structures for both of the doped series. The only exception was for Cu 12 Sb 4-x Bi x S 13 with x = 0.5, which showed a secondary phase, implying that this value is above the solubility limit of Bi in Cu 12 Sb 4 S 13 (12%). A linear increase in the lattice parameter a in both Zn- and Bi-doped tetrahedrite samples was observed with increasing dopant concentration. The estimated elemental compositions from EDX data are in line with the stoichiometric ratio expected for the compounds formed. The morphologies of samples were investigated using SEM and TEM, revealing the formation of smaller particle sizes upon  incorporation of  Zn. Incorporation of Zn or Bi into Cu 12 Sb 4 S 13 led to an increase in band gap energy. The estimated band gap energies of Cu 12-x Zn x Sb 4 S 13 films ranges from 1.49 to 1.6 eV, while the band gaps of Cu 12 Sb 4-x Bi x S 13 films increases from 1.49 to 1.72 eV with increasing x.

Background and Aims: We aimed to explore the association between blood pressure, intracranial atherosclerotic stenosis (ICAS) risks and ICAS burden in the Chinese population., Methods: A retrospective hospital-based multi-center case-control study with large sample size was conducted. 1055 ICAS patients and 1296 non-ICAS subjects with complete clinical information and intracranial artery evaluation were identified between 2014 and 2019. Cerebral arteries were evaluated by magnetic resonance angiography, and/or computed tomography, and/or digital subtraction angiography. Two or more neurologists were involved in reading and assessment of images. The association between ICAS and burden of ICAS with blood pressure was evaluated with univariate logistic models and multivariate logistic models., Results: With every increase of 10 mmHg in systolic blood pressure, diastolic blood pressure and pulse pressure, the odds of ICAS increased by 32%, 28% and 35% in multivariate analysis, respectively (odds ratio = 1.32, 1.28, and 1.35 respectively, all p < 0.001). Similarly, every increment of 10 mmHg in systolic blood pressure and pulse pressure was associated with an increased risk of ICAS burden (each odds ratio = 1.08, p < 0.05)., Conclusions: Systolic blood pressure, diastolic blood pressure, and pulse pressure were associated with the risk of ICAS in a dose-response manner. Moreover, higher systolic blood pressure and pulse pressure could lead to higher ICAS burdens., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: The present study aimed to compare the efficacy and tolerability of different blood pressure (BP)-lowering strategies., Methods: Randomized controlled trials that compared various antihypertensive treatments and stroke outcomes were included. Eligible trials were categorized into three scenarios: single or combination antihypertensive agents against placebos; single or combination agents against other agents; and different BP-lowering targets. The primary efficacy outcome was the risk reduction pertaining to strokes. The tolerability outcome was the withdrawal of drugs, owing to drug-related side effects (PROSPERO registration number CRD42018118454 [20/12/2018])., Results: The present study included 93 trials (average follow-up duration, 3.3 years). In the pairwise analysis, angiotensin-converting enzyme inhibitors (ACEis) and beta-blockers (BBs) were inferior to calcium channel blockers (CCBs) (odds ratio [OR], 1.123; 95% confidence interval [CI], 1.008 to 1.252) (OR, 1.261; 95% CI, 1.116 to 1.425) for stroke prevention, BB was inferior to angiotensin II receptor blockers (ARB) (OR, 1.361; 95% CI, 1.142 to 1.622), and diuretics were superior to ACEi (OR, 0.871; 95% CI, 0.771 to 0.984). The combination of ACEi+CCB was superior to ACEi+diuretic (OR, 0.892; 95% CI, 0.823 to 0.966). The network meta-analysis confirmed that diuretics were superior to BB (OR, 1.34; 95% CI, 1.11 to 1.58), ACEi+diuretic (OR, 1.47; 95% CI, 1.02 to 2.08), BB+CCB (OR, 2.05; 95% CI, 1.05 to 3.79), and renin inhibitors (OR, 1.87; 95% CI, 1.25 to 2.75) for stroke prevention. Regarding the tolerability profile, the pairwise analysis revealed that ACEi was inferior to CCB and less tolerable, compared to the other treatments., Conclusions: Monotherapy using diuretics, CCB, or ARB, and their combinations could be employed as first-line treatments for stroke prevention in terms of efficacy and tolerability.