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Ting-Ting Yang,1,&ast; Ze-Yi Wang,1,&ast; Ze-Xin Fan,1 Bo-Yi Yuan,1 Lin Ma,1 Jian-Feng Lu,1 Pen-Ju Liu,1 Yang He,2 Guang-Zhi Liu1 1Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of China; 2Department of Neurology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guang-Zhi Liu, Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of China, Tel +86-10-64456149, Fax +86-10-64456119, Email guangzhi2002@hotmail.comObjective: This study aimed to initially investigate the efficacy and safety of low-dose tocilizumab combined with glucocorticoid for the treatment of very-late-onset myasthenia gravis (VLOMG).Methods: We conducted a retrospective study in VLOMG patients who were administered intravenous methylprednisolone therapy and subsequently received low-dose oral corticosteroid, in combination with intravenous injection of tocilizumab given once every month for three months.Results: Five patients (mean age 75.0 ± 4.5 years) were included, and all of them were new-onset, and anti-acetylcholine receptor (AChR) antibody-positive generalized MG. The Quantitative Myasthenia Gravis Scale (QMGS) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores before treatment were 15.4 ± 4.3 and 9.6 ± 2.3, respectively, and they exhibited a continuously decreasing trend after the first, second, and third injection of tocilizumab until 6 months after treatment. At 6 months post-treatment, the QMGS and MG-ADL scores were 5.0 ± 2.9 and 2.0 ± 1.2, respectively, and the difference between scores at baseline and 6-month follow-up was significant (P = 0.005 and P < 0.0001, respectively). No serious adverse drug reactions were reported in any patient during the study period.Discussions and Conclusion: The therapeutic efficacy of tocilizumab in VLOMG remains uncertain. The results from our study support the efficacy and safety of this combination treatment option for VLOMG, and strongly suggests the therapeutic potential of tocilizumab in VLOMG. However, considering the limitation of retrospective nature and small sample size in this study, prospective randomized controlled studies including a larger sample size of selected patients are needed to validate our results.Keywords: very late-onset myasthenia gravis, immunotherapy, tocilizumab, glucocorticoid

Guang-Zeng Liu,1 Yan-Gu Pan,2 Bing-Bing Li,1 Xiang-Ling Hou,3 Da-Jun Zhang11Faculty of Psychology, Research Center of Mental Health Education, Southwest University, Chongqing 400715, People’s Republic of China; 2Research Institute of Social Development, Southwestern University of Finance and Economics, Chengdu 610052, People’s Republic of China; 3School of Psychology and Cognitive Science, East China Normal University, Shanghai 200062, People’s Republic of ChinaBackground: There is some research on school climate impact on adolescent alcohol use in the Western social context; however, there is no research on school climate impact on adolescent alcohol use in China. This study aimed to explore the effect of school climate on Chinese adolescents’ alcohol use, and the moderating role of psychological suzhi between them.Methods: A total of 801 adolescents (45.8% boys, 14.96±1.66 years) completed self-reports on school climate, psychological suzhi, and alcohol use.Results: Moderation analyses revealed that both school climate and psychological suzhi significantly negatively predicted adolescents’ alcohol use, and the interaction of school climate and psychological suzhi significantly positively predicted adolescents’ alcohol use. Moreover, the effect of school climate on adolescents’ alcohol use was stronger for low psychological suzhi adolescents than high psychological suzhi adolescents.Conclusions: We can build good school climate by formulating of national level legal and regulations and good social norms, and use mature interventions or cultivation strategies to improve adolescents’ psychological suzhi in order to better play its role in protection.Keywords: school climate, psychological suzhi, alcohol use, adolescents

This preliminary study investigates the current situation of school library support of K-12 health education in China. A survey of 42 school librarians and 115 K-12 teachers from selected schools was conducted to find out their views about school library's role in school health education and their current practice of library use in health teaching. Collection and circulation statistics were gathered from 29 schools where the Hua Xia 2000 school library automation system has been in operation. Research findings indicate that Chinese school libraries' involvement in and support of health education has been rather limited, both in student/teacher services and in collection development. [ABSTRACT FROM AUTHOR]

Taking Liangshui River, the reclaimed water-receiving river in Beijing, as the research area, the types, detection frequencies, and concentrations of 16 antibiotics in water and sediment were analyzed, and their temporal-spatial variation and occurrence characteristics were discussed. The results showed that nine and 13 target antibiotics were detected in the water and sediment of Liangshui River, with the antibiotic concentration ranges of ND-116.68 ng·L -1 and ND-235.42 ng·g -1 , respectively. The main antibiotics in water were ofloxacin and clarithromycin, and the main antibiotic in sediment was ofloxacin. The total concentration of antibiotics in water and sediment showed a gradual decrease from the upstream to the downstream in the Liangshui River mainstream, and the concentration of antibiotics in tributaries was higher than that in the mainstream. The inflow of tributaries had an obvious impact on the antibiotic concentration in water for the Liangshui River but had little impact on its sediment. The total concentration of antibiotics in water and sediment during the dry season was generally higher than that during the wet season. The detected antibiotics with the highest concentration were quinolones in water during the wet season and macrolides in the dry season. Quinolones had the highest concentration in sediment in both seasons. The ecological risk assessment results showed that clarithromycin had a low risk in water in the dry season and sediment in both seasons, whereas the other antibiotics had no risk. The combined ecological risk and the most sensitive trophic level ecological risk assessment showed that all sampling sites had low risk or no risk, and the risk of the dry season was generally greater than that of the wet season. The risk values of some sampling points were close to the medium risk threshold during the dry season, which requires further attention.

Background: The prevention of coronary artery disease (CAD) faces dual challenges: the aspirin-induced gastrointestinal injury, and the residual cardiovascular risk after statin treatment. Geraniol acetate (Gefarnate) is an anti-ulcer drug. It was reported that geraniol might participate in lipid metabolism through a variety of pathways. The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia., Methods: In this prospective, open-label, randomized, controlled trial, 69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group, received gefarnate (100 mg/3 times a day) combined with statin and statin alone, respectively. At baseline and after one-month treatment, the levels of plasma triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol were tested., Results: After one-month gefarnate treatment, triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L ( P = 0.0018), LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L ( P = 0.0004), HDL-C level increased from 0.97 mmol/L to 1.17 mmol/L ( P = 0.0228). Based on statin therapy, gefarnate could significantly reduce the plasma triglyceride level ( P = 0.0148) and increase the plasma HDL-C level ( P = 0.0307). Although the LDL-C and total cholesterol levels tended to decrease, there was no statistically significant difference., Conclusions: The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia. This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients., (© 2024 JGC All rights reserved; www.jgc301.com.)

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5 , Atg16l1 , and Atg7 , or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1 -knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.

Objective: To analyze the clinicopathological features and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement, aiming enhance its recognition and prevent misdiagnosis. Methods: The clinicopathological features, immunophenotype, and fluorescence in situ hybridization (FISH) results of six cases diagnosed with IRF4 rearrangement-positive B-cell lymphoma at the Affiliated Hospital of Xuzhou Medical University from 2015 to 2023 were retrospectively analyzed. Additionally, a comprehensive review of the literature was conducted. Results: Six patients with IRF4 rearrangement-positive large B-cell lymphoma were included. Patients 1 to 5 included three males and two females with a median age of 19 years ranging from 11 to 34 years. Four patients presented with head and neck lesions, while the other one had a breast nodule; all were in clinical Ann Arbor stages I to Ⅱ. Morphologically, entirely diffuse pattern was present in two cases, purely follicular pattern in one case, and diffuse and follicular patterns in other two cases. The tumor cells, predominantly centroblasts mixed with some irregular centrocytes, were of medium to large size, with a starry sky appearance observed in two cases. Immunophenotyping revealed all cases were positive for bcl-6 and MUM1, with a Ki-67 index ranging from 70% to 90%, and CD10 was positive in two cases. IRF4 rearrangement was confirmed in all cases by FISH analysis, with dual IRF4/bcl-6 rearrangements identified in two cases, leading to a diagnosis of LBCL-IRF4. Case 6, a 39-year-old female with a tonsillar mass and classified as clinical Ann Arbor stage Ⅳ, displayed predominantly diffuse large B-cell lymphoma (DLBCL) morphology with 20% high-grade follicular lymphoma characteristics. Immunohistochemistry showed negative CD10 and positive bcl-6/MUM1, with a Ki-67 index of approximately 80%. Triple rearrangements of IRF4/bcl-2/bcl-6 were identified by FISH, leading to a diagnosis of DLBCL with 20% follicular lymphoma (FL). All six patients achieved complete remission after treatment, with no progression or relapse during a follow-up period of 31-100 months. Conclusions: Large B-cell lymphoma with IRF4 rearrangement is a rare entity with pathological features that overlap with those of FL and DLBCL. While IRF4 rearrangement is necessary for diagnosing LBCL-IRF4, it is not specific and requires differentiation from other aggressive B-cell lymphomas with IRF4 rearrangement.

Background: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling., Methods: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening., Results: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m 2 , and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%., Conclusions: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes., (© 2024. The Author(s).)

Background: The increasing uranium containing wastes generated during uranium mining and finishing pose a huge threat to the environment and human health, and thus robust strategies for on-site monitoring of uranium pollutant are of great significance for environmental protection around uranium tailings., Results: Herein, a facile "turn-on" colorimetric platform that can achieve uranium detection by spectrometry and naked eyes was developed based on the uranium-enhanced nanozyme activity of covalent organic framework (JUC-505). Thanks to the extended π-conjugated skeleton and donor-acceptor (D-A) structure, JUC-505 exhibited superior photo-activated nanozyme activity, which would be prohibited when the cyano group in JUC-505 skeleton was transformed to the amidoxime group. Further results elucidated that the coordination of uranium with amidoxime groups led to the electron transfer between uranium and the JUC-505-AO skeleton, and thus significantly restored the nanozymatic activity of JUC-505-AO with the subsequent remarkable color changes. Moreover, the uranium concentrations in uranium tailing wastewater detected by the present "turn-on" colorimetric method were well agreed with those by ICP-MS, demonstrating a high accuracy of the present method in real samples., Significance: The D-A structured JUC-505 with superior photocatalytic property and nanozymatic activity was applied to facilitate colorimetric detection of uranium, which displays the advantages of low detection limit, excellent selectivity, fast response and simple operation for uranium detection in real samples, and shows a great potential in on-site monitoring of uranium pollutant around uranium tailings as well as nuclear power plant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

CD4 + CD25 + regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4 + CD25 high CD127 low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 10 4 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS., (© 2024. The Author(s).)

As large numbers of people are suffering from gout, an accurate, rapid, and sensitive method for the detection of gout biomarker, uric acid, is important for its effective control, diagnosis, and therapy. Although colorimetric detection methods based on uricase have been considered, they still have limitations as they produce toxic H 2 O 2 and are expensive and not stable. Here, a novel uricase-free colorimetric method was developed for the sensitive and selective detection of uric acid based on the light-induced oxidase-mimicking activity of a new photosensitized covalent organic framework (COF) (2,4,6-trimethylpyridine-3,5-dicarbonitrile-4-[2-(4-formylphenyl)ethynyl]benzaldehyde COF [DCTP-EDA COF]). DCTP-EDA COF has a strong ability to harvest visible light, and it could catalyze the oxidation of 1,4-dioxane, 3,3',5,5'-tetramethylbenzidine under visible light irradiation to produce obvious color changes. With the addition of uric acid, however, the significant inhibition of the oxidase-mimicking activity of DCTP-EDA COF remarkably faded the color, and thus uric acid could be colorimetrically detected in the range of 2.0-150 μM with a limit of detection of 0.62 μM (3σ/K). Moreover, the present colorimetric method exhibited high selectivity; uric acid level in serum samples was successfully determined, and the recoveries ranged from 96.5% to 105.64%, suggesting the high accuracy of the present colorimetric method, which demonstrates great promise in clinical analysis., (© 2024 John Wiley & Sons, Ltd.)

Epigenetics refers to the reversible process through which changes in gene expression occur without changing the nucleotide sequence of DNA. The process is currently gaining prominence as a pivotal objective in the treatment of cancers and other ailments. Numerous drugs that target epigenetic mechanisms have obtained approval from the Food and Drug Administration (FDA) for the therapeutic intervention of diverse diseases; many have drawbacks, such as limited applicability, toxicity, and resistance. Since the discovery of the first proteolysis-targeting chimeras (PROTACs) in 2001, studies on targeted protein degradation (TPD)-encompassing PROTACs, molecular glue (MG), hydrophobic tagging (HyT), degradation TAG (dTAG), Trim-Away, a specific and non-genetic inhibitor of apoptosis protein (IAP)-dependent protein eraser (SNIPER), antibody-PROTACs (Ab-PROTACs), and other lysosome-based strategies-have achieved remarkable progress. In this review, we comprehensively highlight the small-molecule degraders beyond PROTACs that could achieve the degradation of epigenetic proteins (including bromodomain-containing protein-related targets, histone acetylation/deacetylation-related targets, histone methylation/demethylation related targets, and other epigenetic targets) via proteasomal or lysosomal pathways. The present difficulties and forthcoming prospects in this domain are also deliberated upon, which may be valuable for medicinal chemists when developing more potent, selective, and drug-like epigenetic drugs for clinical applications., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To investigate the clinicopathological characteristics, diagnosis and differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) and its collision tumors. Methods: Five cases of IVLBCL were collected, including 2 cases of collision tumors, and 1 case complicated with liver cirrhosis. The morphology and immunophenotype were analyzed. The related literature was reviewed. Results: There were 2 females and 3 males, aged from 53 to 73 years, with a median age of 65 years. The tumors were located in the lower extremities, right cerebellar hemisphere, left kidney, bilateral nasal cavity, and liver, respectively. Cases 2 and 3 were incidentally found in meningioma and renal cell carcinoma tissues, respectively. Case 5 had a background of liver cirrhosis. Morphologically, atypical large lymphoid cells were located in small blood vessels and capillary lumen, with little cytoplasm, hyperchromasia, prominent nucleoli, and obvious mitotic figures. Immunohistochemically, the IVLBCL tumor cells expressed CD20 and PAX5; 2 cases were CD5 positive. One of the 5 cases was GCB phenotype, and 4 cases were non-GCB phenotype. All cases expressed C-MYC (positive rate was 10%-40%). PD-L1 was positive in 4 cases (positive rate was 60%-90%). Ki-67 proliferation index was 70%-90%. CKpan, CD3, TDT, and CD34 were negative. In case 2, meningioma cells were positive for PR, EMA, and vimentin, but negative for CKpan and PD-L1. In case 3, renal carcinoma cells were positive for CKpan, PAX8, EMA, vimentin, CAⅨ and CD10, while PD-L1 was negative. No EBER expression (by in situ hybridization) or C-MYC gene translocation (FISH, break-apart probe) was detected in any of the 5 cases. Three patients were followed up, and all died within 1-13 months. Conclusions: IVLBCL is a highly aggressive lymphoma, with occult clinical manifestations and poor prognosis. Collision tumors of IVLBCL are extremely rare. A better understanding of IVLBCL would help pathologists avoid misdiagnoses.

Background: Transversus abdominis plane block (TAPB) is a block of the abdominal afferent nerve fibers between the internal oblique muscle and the transverse abdominal muscle achieved with local anesthetics. It can effectively block the conduction of the anterior nerve of the abdominal wall and exert a good analgesic effect. However, the effect of combining the block with remimazolam on anesthesia in patients undergoing gastrointestinal tumor surgery is still unclear., Aim: To examine the effects of combining TAPB with remimazolam on the stress response and postoperative recovery of gastrointestinal tumor surgery patients., Methods: A retrospective analysis was conducted on the clinical data of 102 individuals diagnosed with gastrointestinal malignancies who underwent laparoscopic surgery under general anesthesia between April 2020 and June 2023. The patients were categorized into a control group ( n = 51), receiving remimazolam for general anesthesia, and an observation group ( n = 51), receiving TAPB combined with remimazolam for general anesthesia. A comparison was made between both groups in terms of hemodynamic parameters, stress markers, pain levels, recovery quality, analgesic effects, and adverse reactions during the perioperative period., Results: The observation group had significantly higher heart rates at time points 1 min after induction and upon leaving the operating room than the control group ( P < 0.05). The mean arterial pressure at time point T1 in the observation group was significantly higher than that in the control group ( P < 0.05). Five minutes after extubation, the levels of the hormones adrenaline and noradrenaline in the observation group were considerably lower than those in the control group ( P < 0.05). At 12 h, 24 h, and 48 h following surgery, the visual analog scale scores of the observation group were considerably lower than those of the control group ( P < 0.05). The observation group had shorter awakening and extubation times and lower Riker sedation-agitation scale scores than the control group ( P < 0.05). The observation group exhibited considerably fewer effective pump presses, lower fentanyl dosages, and lower incidences of rescue analgesia within 24 h following surgery than the control group ( P < 0.05)., Conclusion: The application effect of TAPB combined with remimazolam general anesthesia in anesthesia of patients undergoing gastrointestinal tumor surgery is good, which is helpful to promote faster recovery after operation., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The NLRP3 inflammasome is involved in the neuroinflammatory pathway of Alzheimer's disease (AD). The aim of this study is to explore the roles and underlying mechanisms of ginkgolide (Baiyu®) on amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and a murine microglial cell line, BV-2. In the present study, the APP/PS1 mice were administered with ginkgolide, followed by a Morris water maze test. The mice were then euthanized to obtain brain tissue for histological and Aβ analysis. Additionally, BV-2 cells were pretreated with ginkgolide and then incubated with Aβ1-42 peptide. NLRP3, ASC, and caspase-1 mRNA and protein expression in brain tissue of mice and BV-2 cells were quantified by real-time PCR and western blotting, as well as reactive oxygen species (ROS) production, interleukin (IL)-1β and IL-18 levels by lucigenin technique and ELISA. Compared with the APP/PS1 mice, ginkgolide-treated mice demonstrated the shortened escape latency, reduced plaques, less inflammatory cell infiltration and neuron loss in the hippocampi of APP/PS1 mice. The levels of NLRP3, ASC, caspase-1, ROS, IL-1β, and IL-18 were also decreased in the brain tissue of APP/PS1 mice or Aβ1-42-treated BV-2 cells following ginkgolide treatment. Ginkgolide exerted protective effects on AD, at least partly by inactivating the NLRP3/caspase-1 pathway.

This study aimed to systematically evaluate the efficacy and safety of different Chinese patent medicines in the treatment of idiopathic membranous nephropathy. The relevant randomized controlled trial(RCT) was retrieved from PubMed, EMbase, Cochrane Library, CNKI, SinoMed, Wanfang, and VIP with the time interval from database inception to December 2022. The Cochrane risk of bias assessment tool was employed to evaluate the quality of the included RCT, and Stata 15.0 and GEMTC to perform the Bayesian network Meta-analysis. Finally, 51 RCTs were included, involving 9 Chinese patent medicines and 3 591 patients. The results of network Meta-analysis showed that in terms of the total effective rate and the increase in plasma albumin, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Bailing Capsules + conventional western medicine, and Tripterygium Glycosides Tablets + conventional western medicine. In terms of reducing 24-hour urine total protein, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Shenfukang Capsules +conventional western medicine, and Huangkui Capsules + conventional western medicine. In terms of reducing serum creatinine, the top three interventions were Shenfukang Capsules + conventional western medicine, Bailing Capsules + conventional western medicine, and Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine. In terms of safety, Chinese patent medicines combined with conventional western medicine had fewer adverse reactions than the control group. The results suggest that Chinese patent medicines combined with conventional western medicine can improve the therapeutic effect on idiopathic membranous nephropathy, and differentiated medications can be adopted according to the specific symptoms of patients in clinical treatment. Further validation needs to be carried out in the future with multi-center, large-sample, and high-quality RCT.

Objective: To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer., Methods: Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve., Results: A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95% CI : 0.644-0.675) vs . 0.608 (95% CI : 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95% CI : 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95% CI : 0.584-0.616) vs . 0.615 (95% CI : 0.599-0.631), P =0.188], but Fine & Gray model showed better calibration., Conclusion: It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.

Objective: To examine the patterning cropped and shaped mesh repair for perineal hernia after abdominoperineal excision (APE) in rectal cancer. Methods: The clinical data of 8 patients with perineal hernia after APE who accepted surgical treatment in the Department of Hepatopancreatobiliary and Hernia Surgery, the First Affiliated Hospital of Fujian Medical University from March 2017 to December 2022 were retrospectively reviewed. There were 3 males and 5 females, aged (67.6±7.2) years (range: 56 to 76 years). Eight patients developed a perineal mass at (11.3±2.9) months (range: 5 to 13 months) after APE. After surgical separation of adhesion and exposing the pelvic floor defect, a 15 cm×20 cm anti-adhesion mesh was fashioned as a three-dimensional pocket shape to fit the pelvic defect, then fixed to the promontory or sacrum and sutured to the pelvic sidewalls and the anterior peritoneum, while two side slender slings were tailored in front of the mesh and fixed on the pectineal ligament. Results: The repair of their perineal hernias went well, with an operating time of (240.6±48.8) minutes (range: 155 to 300 minutes). Five patients underwent laparotomy, 3 patients tried laparoscopic surgery first and then transferred to laparotomy combined with the perineal approach. Intraoperative bowel injury was observed in 3 patients. All patients did not have an intestinal fistula, bleeding occurred. No reoperation was performed and their preoperative symptoms improved significantly. The postoperative hospital stay was (13.5±2.9) days (range: 7 to 17 days) and two patients had postoperative ileus, which improved after conservative treatment. Two patients had a postoperative perineal hernia sac effusion, one of them underwent placement of a tube to puncture the hernia sac effusion due to infection, and continued irrigation and drainage. The postoperative follow-up was (34.8±14.0) months (range: 13 to 48 months), and 1 patient developed recurrence in the seventh postoperative month, no further surgery was performed. Conclusions: Surgical repair of the perineal hernia after APE can be preferred transabdominal approach, routine application of laparoscopy is not recommended, combined abdominoperineal approach can be considered if necessary. The perineal hernia after APE can be repaired safely and effectively using the described technique of patterning cropped and shaped mesh repair.

Background: Increasing evidence indicates the importance of CD8 + T cells in autoimmune attack against CNS myelin and axon in multiple sclerosis (MS). Previous research has also discovered that myelin-reactive T cells have memory phenotype functions in MS patients. However, limited evidence is available regarding the role of CD8 + memory T cell subsets in MS. This study aimed to explore potential antigen-specific memory T cell-related biomarkers and their association with disease activity., Methods: The myelin oligodendrocyte glycoprotein (MOG)-specific CD8 + memory T cell subsets and their related cytokines (perforin, granzyme B, interferon (IFN)-γ) and negative co-stimulatory molecules (programmed cell death protein 1 (PD-1), T- cell Ig and mucin domain 3 (Tim-3)) were analyzed by flow cytometry and real-time PCR in peripheral blood of patients with relapsing-remitting MS., Results: We found that MS patients had elevated frequency of MOG-specific CD8 + T cells, MOG-specific central memory T cells (T CM ), MOG-specific CD8 + effector memory T cells (T EM ), and MOG-specific CD8 + terminally differentiated cells (T EMRA ); elevated granzyme B expression on MOG-specific CD8 + T CM ; and, on MOG-specific CD8 + T EM , elevated granzyme B and reduced PD-1 expression. The Expanded Disability Status Scale score (EDSS) in MS patients was correlated with the frequency of MOG-specific CD8 + T CM , granzyme B expression in CD8 + T CM , and granzyme B and perforin expression on CD8 + T EM , but with reduced PD-1 expression on CD8 + T EM ., Conclusion: The dysregulation of antigen-specific CD8 + memory T cell subsets, along with the abnormal expression of their related cytokines and negative co-stimulatory molecules, may reflect an excessive or persistent inflammatory response induced during early stages of the illness. Our findings strongly suggest positive regulatory roles for memory T cell populations in MS pathogenesis, probably via molecular mimicry to trigger or promote abnormal peripheral immune responses. Furthermore, downregulated PD-1 expression may stimulate a positive feedback effect, promoting MS-related inflammatory responses via the interaction of PD-1 ligands. Therefore, these parameters are potential serological biomarkers for predicting disease development in MS., 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 Liu, Yang, Fan, Yuan, Ma, Wang, Lu, Yuan, Zou, Zhang and Liu.)

Objective: This study aims to identify relevant risk factors, assess the interactions between variables, and establish a predictive model for ischemic stroke (IS) in patients with cardiac myxoma (CM) using the Bayesian network (BN) approach., Methods: Data of patients with CM were collected from three tertiary comprehensive hospitals in Beijing from January 2002 to January 2022. Age, sex, medical history, and information related to CM were extracted from the electronic medical record system. The BN model was constructed using the tabu search algorithm, and the conditional probability of each node was calculated using the maximum likelihood estimation method. The probability of each node of the network and the interrelationship between IS and its related factors were qualitatively and quantitatively analyzed. A receiver operating characteristic (ROC) curve was also plotted. Sensitivity, specificity, and area under the curve (AUC) values were calculated and compared between the BN and logistic regression models to evaluate the efficiency of the predictive model., Results: A total of 416 patients with CM were enrolled in this study, including 61 with and 355 without IS. The BN model found that cardiac symptoms, systemic embolic symptoms, platelet counts, and tumor with high mobility were directly associated with the occurrence of IS in patients with CM. The BN model for predicting CM-IS achieved higher scores on AUC {0.706 [95% confidence interval (CI), 0.639-0.773]} vs. [0.697 (95% CI, 0.629-0.766)] and sensitivity (99.44% vs. 98.87%), but lower scores on accuracies (85.82% vs. 86.06%) and specificity (6.56% vs. 11.48%) than the logistic regression model., Conclusion: Cardiac symptoms, systemic embolic symptoms, platelet counts, and tumor with high mobility are candidate predictors of IS in patients with CM. The BN model was superior or at least non-inferior to the traditional logistic regression model, and hence is potentially useful for early IS detection, diagnosis, and prevention in clinical practice., 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., (© 2023 Ma, Cai, Qiao, Fan, Fang, Wang and Liu.)

Cardioembolic stroke, referred to as cardiogenic stroke, is a clinical syndrome in which emboli from the heart pass through the circulatory system and cause cerebral artery embolism and corresponding brain dysfunction. Compared to other subtypes of ischemic stroke, cardiogenic stroke presents with more etiologies, greater severity, worse prognosis, and a higher recurrence rate. In this minireview, we provide new insights into the etiological classification, diagnostic methods, and interventions of cardiogenic stroke., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Cardiac myxoma (CM) is an important etiology of stroke in young adults, but studies on CM-related ischemic stroke (CM-IS) are limited and conflicting. Hence, we investigated clinical characterizations, risk factors of CM-IS, and short-term survival after surgical resection., Methods: We performed a retrospective analysis of data from all CM patients at three referral management centers and conducted follow-up examination., Results: Among 414 CM patients, 402 were recruited for further analysis, including 54 patients with CM-IS and 348 patients with CM without stroke (Non-stroke). In the acute phase, patients presented with NIHSS 3 (interquartile range: 0-10) and clinical presentation comprising neurological, cardiac and constitutional symptoms. Multivariate analysis showed that the factors associated with an increased risk of CM-IS were tumor width < 30 mm [OR = 2.652, 95% CI: 1.061-6.627, P = 0.037], tumors with high-mobility (OR = 2.700, 95% CI: 1.357-5.371, P = 0.005), thrombus on the tumor surface (OR = 1.856, 95% CI: 1.003-3.434, P = 0.049), and lower B-type natriuretic peptide (BNP) levels (OR = 0.995, 95% CI: 0.989-0.999, P = 0.047). The overall three-year survival rate was 95.7% (95% CI: 94.9-96.5) in CM-IS patients who underwent surgery., Conclusions: CM-IS patients had mild or moderate neurologic deficits with various presentations at disease onset. Narrower tumor width, tumors with high-mobility, thrombus on the tumor surface, and lower BNP levels are potential predictors of CM-IS development. Surgical removal of CM is safe and efficacious in patients with CM-IS., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Few studies have reported the burden of generalized pustular psoriasis (GPP), a severe and potentially life-threatening skin disease, especially at a national level., Objectives: The aim of this study is to estimate the nationwide burden of GPP in China and make a systemic review of the published data., Methods: We conducted a population-based study using Urban Basic Medical Insurance in China from 2012 to 2016. GPP cases were identified by primary diagnoses including the international classification of Diseases codes (ICD-10: L40.1 and ICD-9: 694.3). A systematic review was conducted using relevant databases up to January 2022., Results: The crude prevalence and incidence of GPP in 2016 were 1.403 (95% confidence interval [CI]: 1.115-1.691) and 0.629 (95% CI: 0.483-0.775) per 100,000 person-years, respectively. The rates were higher in males than in females for both prevalence (1.429 vs. 1.135) and incidence (0.635 vs. 0.520). The prevalence and incidence showed a bimodal age distribution, with the first peak occurring in the 0- to 3-year age-group and the second peak occurring in the 30- to 39-year age-group. The per capita total cost per year for 1 patient with GPP was 609.26 (± 45.77) US dollars. Seven studies were identified in a systematic review, according to which the prevalence (per 100,000) of GPP tended to be higher in Asian countries (0.746-8.178 in Japan and 12.230 in Korea) than in France (0.176), Sweden (6.25), and Brazil (0.7)., Conclusions: This is the largest study concerning the disease burden of GPP, and in this study, the prevalence seemed to be higher in Asia. Although the direct economic burden of GPP did not seem high during the study period, the future usage of biologics and the humanistic burden should also be considered for policy-related decision-making., (© 2023 S. Karger AG, Basel.)

The toxicity of microplastics (MPs) to marine microalgae has raised much concern. However, research at metabolic level is quite limited. In this study, the physiological and metabolic effects of polystyrene (PS) and aged polystyrene (A-PS) MPs on Dunaliella salina were investigated. Both PS and A-PS inhibited the growth of microalgae, but promoted the pigment synthesis in algal cells. The oxidative stress analysis indicated that PS and A-PS induced high production of reactive oxygen species (ROS), and caused oxidative damage to algal cells. Particularly, the highest ROS level in PS and A-PS groups were 1.70- and 2.24-fold of that in the control group, respectively. Untargeted metabolomics analysis indicated that PS and A-PS significantly increased the differential metabolites. Compared with the control group, the significant upregulation of glycerophospholipids metabolites illustrated that severe membrane lipid peroxidation occurred in the MPs groups. Metabolic pathways analysis showed that PS and A-PS perturbed the amino acid-related metabolic pathways. In particular, the amino acid biosynthesis and ATP-binding cassette (ABC) transporter pathways were significantly upregulated, thus promoting nitrogen storage and transmembrane transport in Dunaliella salina. Transmembrane transport requires a large amount of ATP; as a result, algal cell division is inhibited. In addition, A-PS stimulated more active glutathione metabolism than PS. These results enrich the understanding of the toxicity of PS MPs to microalgae at the metabolic level, and are helpful for further assessing the ecological impacts of MPs on microalgae., 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 Ltd. All rights reserved.)

In condensed-matter systems, electrons are subjected to two different interactions under certain conditions. Even if both interactions are weak, it is difficult to perform perturbative calculations due to the complexity caused by the interplay of two interactions. When one or two interactions are strong, ordinary perturbation theory may become invalid. Here we consider undoped graphene as an example and provide a non-perturbative quantum-field-theoretic analysis of the interplay of electron-phonon interaction and Coulomb interaction. We treat these two interactions on an equal footing and derive the exact Dyson-Schwinger (DS) integral equation of the full Dirac-fermion propagator. This equation depends on several complicated correlation functions and thus is difficult to handle. Fortunately, we find that these correlation functions obey a number of exact identities, which allows us to prove that the DS equation of full fermion propagator is self-closed. After solving this self-closed equation, we obtain the renormalized fermion velocity and show that its energy (momentum) dependence of renormalized fermion velocity is dominantly determined by the electron-phonon (Coulomb) interaction. In particular, the renormalized velocity exhibits a logarithmic momentum dependence and a non-monotonic energy dependence., (© 2022 IOP Publishing Ltd.)

Objective: This study aimed to explore risk factors, clinical features, and prognosis of patients with hypertrophic cardiomyopathy (HCM) complicated by ischemic stroke (IS)., Methods: We conducted a retrospective analysis of all HCM patient data and a 1-year follow-up study., Results: Totally, 506 patients with HCM, including 71 with IS, were enrolled. Older age (≥63 years) was associated with an increased risk of IS in HCM patients (OR = 1.045, 95% CI: 1.018-1.072, p = 0.001). Among 37 patients complicated by IS, 22 (59.5%, 22/37) manifested as cardioembolism (CE) subtype, and 13 (35.1%, 3/37) small artery occlusion (SAO) subtype, according to TOAST classification. In the acute phase, the IS patients presented with NIHSS 4 (interquartile range: 1, 10). Multi-infarction was more common than single infarction (72.7 vs. 27.3%), while cortical + subcortical infarction (CE group: 50%) or subcortical infarction (SAO group: 53.8%) constituted most IS cases. Additionally, the blood supply areas of anterior circulation (CE group: 45.5%; SAO group: 92.3%) or anterior + posterior circulation (CE group: 50%) were mainly involved. The 1-year survival rate of HCM patients with concomitant IS was 81.8%, and IS was associated with 1-year all-cause death in HCM patients (HR = 5.689, 95% CI: 1.784-18.144, p = 0.003)., Conclusion: Older age is a risk factor for IS occurrence in HCM patients. Patients with HCM complicated by IS had mild or moderate neurologic deficits at disease onset. CE and SAO subtypes predominate in patients with concomitant IS, especially the former. Multiple cortical and subcortical infarctions are their neuroimaging characteristics, mainly involving the anterior circulation or anterior + posterior circulation. Is is a risk factor for all-cause death in HCM patients within 1 year., 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 Lu, Fan, Li, Wang, Ma, Yuan, Yang, Liu and Liu.)

Objective: To analyze the clinical features, risk factors and prognosis of idiopathic dilated cardiomyopathy (DCM) complicated with ischemic stroke (IS) (DCM-IS). Methods: The clinical data of patients with idiopathic DCM ( n =613) in Beijing Anzhen Hospital, Liangxiang Hospital and Fuxing Hospital from January 2016 to December 2020 were retrospectively collected, and among them, 123 cases were DCM-IS. Clinical features of patients with DCM-IS were summarized and multivariate logistic regression model was utilized to analyze the independent risk factors of DCM-IS. Furthermore, 1-year follow-up was conducted and Kaplan-Meier curve was adopted to analyze the prognosis of DCM, using all-cause death and heart transplantation as adverse outcomes. Results: Among the 70 patients with DCM-IS, 6 patients (8.6%, 6/70) were in accordance with the subtype of large artery atherosclerosis, and 47 patients (67.1%, 47/70) were in line with the subtype of cardiogenic embolism, and small artery occlusion subtype (ie, lacunar infarction) were detected in 17 cases (24.3%, 17/70). Hypertension [odds ratio ( OR )=1.617, 95% confidence interval ( CI ): 1.049-2.491, P =0.029], hyperlipidemia ( OR =1.918, 95% CI : 1.198-3.073, P =0.007), atrial fibrillation (AF) ( OR =1.617, 95% CI : 1.016-2.572, P =0.043), lower estimated glomerular filtration rate (eGFR) ( OR =0.986, 95% CI : 0.977-0.996, P =0.005) and a higher incidence of intracardiac thrombus ( OR =6.127, 95% CI : 3.174-11.827, P <0.001) were risk factors for DCM-IS. The overall 1-year survival rate was lower in DCM-IS patients (70.7%) than DCM patients without stroke (83.6%, P =0.004), and the main causes of death included obstinate heart failure (3 cases of DCM-IS, and 5 cases of non-DCM-IS) and malignant arrhythmia (DCM-IS) (22 cases of DCM-IS, and 18 cases of non-DCM-IS). Conclusions: Among IS patients with idiopathic DCM, cardioembolism is the most common, followed by lacunar infarction, and the large-artery atherosclerotic subtype is the least common.Hypertension, hyperlipidemia, AF, lower eGFR value and higher incidence of intracardiac thrombus are risk factors for DCM-IS. DCM patients complicated with IS have poor short-term prognosis, and obstinate heart failure and malignant arrhythmia are their main causes of death.

Cardiogenic stroke, manifested as a clinical syndrome in which emboli from the heart and aortic arch pass through the circulation and cause cerebral artery embolism and corresponding brain dysfunction, accounts for 20% to 30% of all ischemic strokes. Regarding the etiological classification, the boundary between cardiogenic stroke and cryptogenic stroke, especially embolic stroke of undetermined source (ESUS), as well as aortic arch atheromas categorization remain uncertain. Concerning the diagnosis, the criteria need to be formulated and unified, and thus the author proposes new diagnostic criteria. With regard to the treatment, anticoagulation therapy should be started or restarted several days to several weeks after the onset of stroke (e.g., atrial fibrillation-related), and treatment during acute phase and for prevention of stroke recurrence should be initiated after multi-disciplinary consultation.

Alzheimer's disease (AD) is an irreversible degenerative illness of the central nervous system with characteristic histological alterations, known as amyloid plaques and neurofibrillary tangles (NFT). Aggregation of plaques and tangles in the brain induces neurotoxicity and synaptic dysfunction, eventually contributing to neuronal cell death and neurodegeneration. Recent studies have revealed that COVID-19 has a great impact on the development of AD, directly or indirectly, by facilitating the accumulation of amyloid plaques, causing altered functional brain integrity or increasing the phosphorylation rate of tau protein. As two important bioactive components of Ginkgo biloba extract (GbE), ginkgolides and bilobalide (BB) have been reported to show neuroprotective effects in AD via multiple mechanisms such as anti-excitotoxicity, anti-inflammatory and anti-oxidative activities. Intriguingly, ginkgolides and BB also seem to demonstrate antiviral properties against COVID-19 by inhibiting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. Herein, we review studies on the neuroprotective and antiviral mechanisms of ginkgolides and bilobalide, as well as their therapeutic potential against AD and COVID-19.

Objective: This study aimed to identify risk factors and create a predictive model for ischemic stroke (IS) in patients with dilated cardiomyopathy (DCM) using the Bayesian network (BN) approach., Materials and Methods: We collected clinical data of 634 patients with DCM treated at three referral management centers in Beijing between 2016 and 2021, including 127 with and 507 without IS. The patients were randomly divided into training (441 cases) and test (193 cases) sets at a ratio of 7:3. A BN model was established using the Tabu search algorithm with the training set data and verified with the test set data. The BN and logistic regression models were compared using the area under the receiver operating characteristic curve (AUC)., Results: Multivariate logistic regression analysis showed that hypertension, hyperlipidemia, atrial fibrillation/flutter, estimated glomerular filtration rate (eGFR), and intracardiac thrombosis were associated with IS. The BN model found that hyperlipidemia, atrial fibrillation (AF) or atrial flutter, eGFR, and intracardiac thrombosis were closely associated with IS. Compared to the logistic regression model, the BN model for IS performed better or equally well in the training and test sets, with respective accuracies of 83.7 and 85.5%, AUC of 0.763 [95% confidence interval (CI), 0.708-0.818] and 0.822 (95% CI, 0.748-0.896), sensitivities of 20.2 and 44.2%, and specificities of 98.3 and 97.3%., Conclusion: Hypertension, hyperlipidemia, AF or atrial flutter, low eGFR, and intracardiac thrombosis were good predictors of IS in patients with DCM. The BN model was superior to the traditional logistic regression model in predicting IS in patients with DCM and is, therefore, more suitable for early IS detection and diagnosis, and could help prevent the occurrence and recurrence of IS in this patient cohort., 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 Fan, Wang, Fang, Ma, Niu, Wang, Lu, Yuan and Liu.)

Ring-finger protein 5 (RNF5) is an E3 ubiquitin ligase which is expressed in a variety of human tissues. RNF5 is involved in the regulation of endoplasmic reticulum stress, inflammation, and innate immunity and plays an important role in the occurrence and development of various tumors. However, the role of RNF5 in cardiac hypertrophy has not been reported. In this study, we found the expression of RNF5 was increased in the hearts of mice with pathological cardiac hypertrophy. The loss-of-function research demonstrated that RNF5 deficiency exacerbated cardiac hypertrophy, whereas gain-of-function studies revealed that overexpression of RNF5 had opposite effects. The stimulator of interferon genes (STING) is a signaling molecule that can activate type I interferon immunity, which can meditate inflammation and immune response in many diseases. The protein-protein interaction experiments confirmed that STING interacted with RNF5. Further studies showed that RNF5 inhibited cardiac hypertrophy by promoting STING degradation through K48-linked polyubiquitination. Therefore, we defined RNF5 as importantly regulated signaling for cardiac hypertrophy., (© 2022. The Author(s).)

Background: Pseudomyxoma peritonei (PMP) is an extremely rare condition. Information regarding the disease burden of PMP in developing countries is limited. This study aimed to determine the epidemiology of PMP in China., Methods: PMP data were extracted from the national databases of Urban Basic Medical Insurance. All cases were identified using the International Classification of Diseases (ICD) codes and Chinese diagnostic terms. The national prevalence from 2012 to 2016 and incidence in 2016 were estimated., Results: In total, 153 patients with PMP were identified. The crude prevalence of PMP in 2016 was 2.47 (95% confidence interval [CI] 1.71 to 3.23) per million person-year, with a higher prevalence in females than males. Prevalence increased with age, with the first peak in those aged 15-29 years and the highest in those aged >80 years. The crude incidence of PMP in 2016 was 1.19 (95% CI 0.59 to 1.78) per million person-years. Similar to the prevalence, the rates were higher in women than in men. The incidence also increased with age, with the highest prevalence in those aged >80 years. Besides, the most frequent comorbidities before and after the first diagnosis of PMP were unspecified secondary malignancies and malignancies of unspecified sites, followed by abdominal malignant tumours., Conclusions: The rate of PMP was lower in mainland China than in European countries and increased with advancing age. Women were more likely to have PMP than men. Furthermore, an insufficient understanding of this rare disease presents a major challenge in accurately evaluating the disease burden., 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. Published by Elsevier Ltd.)

Importance: China is experiencing a sustained increase in childhood cancer. However, whether differences exist in disease burden by ethnicity remains unclear., Objective: To compare differences in cancer diagnoses and health care utilization in Inner Mongolia among children subgrouped by ethnicity (Han vs Mongolian), sex, and age., Design, Setting, and Participants: This retrospective cohort study in Inner Mongolia, China, used data on children aged 0 to 14 years with cancer from the Inner Mongolia Regional Health Information Platform, which comprises the National Basic Medical Insurance database and the Inner Mongolia cause-of-death reporting system, from January 1, 2013, to December 31, 2019. Ethnicities analyzed included Han and Mongolian; patients of other ethnicities were not included in the analysis because of the small sample size. Cancer was broadly defined as a primary malignant tumor or hematologic cancer; benign central nervous system tumors were also included. A 2-year washout period was used to exclude prevalent cases. After diagnosis, the patients were followed up until the date of death or the end of the insured status, whichever came first., Exposures: Ethnicity (Han vs Mongolian), sex (male vs female), and age (0-4, 5-9, and 10-14 years)., Main Outcomes and Measures: Crude incidence, 5-year prevalence, and survival rates at 1 year and 3 years after diagnosis; health care utilization, represented by medical costs during the first year and first 3 years after diagnosis; and hospital attendance with level (tertiary vs secondary and lower-level hospitals) and location of each unique visit., Results: From 2013 to 2019, 1 106 684 (2013), 1 330 242 (2014), 1 763 746 (2015), 2 400 343 (2016), 2 245 963 (2017), 2 901 088 (2018), and 2 996 580 (2019) children aged 0 to 14 years were registered in the NBMI database. Among the 2 996 580 children enrolled in 2019, the mean (SD) age was 6.8 (4.3) years, of whom 1 572 096 (52.5%) were male, 2 572 091 (85.8%) were Han, and 369 400 (12.3%) were Mongolian. A total of 1910 patients with cancer were identified (1048 were male [54.9%]; 1559 were Han [81.6%], and 300 were Mongolian [15.7%]). There were 764 hematologic cancers (40.0%) and 1146 solid tumors (60.0%). The overall crude incidence of cancer from 2015 to 2019 was 129.85 per million children (95% CI, 123.63-136.06), with a higher incidence among Mongolian than among Han children (155.12 [95% CI, 136.81-173.43] vs 134.39 [95% CI, 127.46-141.32]). The 5-year prevalence was 428.97 per million (95% CI, 405.52-452.42) in 2020, with a higher prevalence among Mongolian than among Han children (568.49 [95% CI, 91.62-645.36] vs 404.34 [95% CI, 379.77-428.91]). The combined 1-year (2015-2019) and 3-year (2015-2017) survival rates were 72.5% (95% CI, 67.5%-77.5%) and 66.8% (95% CI, 61.6%-71.9%), respectively. The 1-year (median [IQR], $1991 [$912-$10 181] vs $3991 [$1171-$15 425]) and 3-year (median [IQR], $2704 [$954-$13 909] vs $5375 [$1283-$22 466]) postdiagnosis costs were lower among Mongolian than among Han children. A higher proportion of Mongolian patients attended low-level hospitals (45.9% vs 17.4%)., Conclusions and Relevance: In this cohort study, Mongolian children had a higher incidence and prevalence of cancer but a lower demand for medical care, suggesting that further investigations are needed to identify mechanisms underlying ethnic disparities and ensure that care is equitable.

Objective: To investigate the short-term clinical effect of the cervical anterior Hybrid surgery in the treatment of two-segment and three-segment cervical spondylosis., Methods: From January 2018 to January 2019, 108 patients who were performed anterior Hybrid surgery with cervical degenerative diseases were collected. The patients were divided into a two-segment group with 52 patients and a three-segment group with 56 patients according to surgical segments. In two-segment group, there were 24 males and 28 females, aged from 35 to 67 years old with an average of(45.94±14.67) years old. In three-segment group, there were 23 males and 33 females, aged from 32 to 65 years old with an average of (47.54±15.34) years old. The outcome indicators of the two groups were compared. Clinical indicators:neck disability index(NDI) was used to evaluate daily life ability, Japanese Orthopedic Association(JOA) score was used to evaluate neurological function improvement, visual analogue scale(VAS) was used to evaluate pain intensity, and general clinical results were graded according to Odom's score. Cervical range of motion (ROM), fusion and complications were measured by X-ray, CT and MRI., Results: All operations were successfully completed and all patients were followed up for more than 12 months. The operation time of two-segment group and three-segment group were 95 to 180 min with an average of(152.30±44.74) min and 110 to 210 min with an average of (165.18±45.86) mins, the blood loss were 20 to 100 ml with an average of (32.88±8.75) ml and 20 to 150 ml with an average of(34.64±10.63) ml respectively which has no statistical differences between the two groups ( P >0.05). Compared with those before surgery, NDI, JOA, VAS and Odom's scores between two groups were significantly improved at 12 months after operation( P <0.05). However, there was no significant difference in the NDI, JOA and Odom's scores between two groups ( P >0.05), and VAS in three-segment group was higher than that in two-segment group. There was no significant difference in C 3 -C 7 cervical mobility between two groups. Surgical incisions healed smoothly in all patients without complication such as spinal cord injury and cerebrospinal fluid leakage. The bone fusion of the two groups were 43 cases (82.69%) and 45 cases(80.35%) respectively. In two-segment group, there were 2 cases of adjacent segmental hyperosteogeny, and there were 3 cases of adjacent segmental hyperosteogeny and 1 case of adjacent posterior longitudinal ligament ossification in the three-segment group. In addition, in three-segment group, there was 1 case of looseness of implants with no obvious clinical symptoms., Conclusion: The anterior Hybrid surgery in treating multi-level cervical spondylosis could not only improve clinical symptoms of patients but also preserve mobility. Meanwhile, the efficacy and safety of Hybrid surgery in different multi-level cervical disc diseases are confirmed, proving its value in clinical practice.

Methods: Overall, 18 rabbits were randomly divided into control, pacing (600 beats/min), and pacing+sac/val groups. The rabbits in the pacing+sac/val cohort received oral sac/val (10 mg/kg twice daily) across the 21-day investigation period. After three weeks, the atrial effective refractory period (AERP) and AF induction rate were compared. HL-1 cultures were exposed to fast pacing (24 h) with and without LBQ657 (active sacubitril form)/valsartan. Western blots were used for detecting Ca v 1.2 and CaMKII expression within atrial muscles of the rabbits and HL-1 cultures of AF model., Results: In comparison to the sham cohort, the AF induction rate was markedly increased together with AERP reduction within pacing cohort. Such changes were markedly rescued through sac/val treatment in pacing+sac/val cohort. The proteomic expression profiles of CaMKII and Ca v 1.2 showed that the CaMKII expression was markedly upregulated, while Ca v 1.2 expression was downregulated in the pacing cohort. Importantly, these effects were absent in pacing+sac/val cohort., Conclusion: Results of this study show that sac/val treatment regulates the expression of CaMKII/Ca v 1.2 and could alter this pathway in atrial rapid electrical stimulation models. Therefore, this investigation could contribute to a novel strategy in AF therapeutics in clinical settings., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Qi Lou et al.)

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular characteristics, differential diagnosis, clinical treatment and prognosis of mixed carcinoma of cervix with adenoid cystic pattern. Methods: Three cases of mixed cervical carcinoma with adenoid cystic pattern were collected at the Affiliated Hospital of Xuzhou University Medical School from 2018 to 2021.The clinicopathological characteristics were analyzed, immunohistochemistry (IHC) and in situ hybridization (ISH) were performed. The related literature was reviewed. Results: The three patients were postmenopausal women with a median age of 74.7 years. The clinical symptom was vaginal bleeding without obvious causes. One case was an endophytic tumor, and the others were exophytic. The median diameter of the three cases was 3.3 cm. Two patients underwent hysterectomy, the tumors infiltrated the external 1/3 and middle 1/3 of the cervix respectively. All the lymph nodes were negative. One patient had a previous biopsy. Microscopically, all three tumors were characterized by a cribriform structure, which were filled with basophilic myxoid substance and surrounded by tubules lined by two layers of cells. The tumor cells had scanty cytoplasm and showed the characteristics of cervical basal-like cells. All three cases were accompanied by high-grade squamous intraepithelial lesions and squamous cell carcinoma, and one also showed a non-specific spindle cell sarcomatoid component. Within the double-layered epithelial structure, the outer epithelium was positive for p63, CD117, p16 INK4a (clone E6H4) and MYB protein and negative for S-100 by IHC. The combined positive score of PD-L1 (clone 22C3) was less than 1 in all three cases. Human papillomavirus (HPV) types 16 and 18 were detected in one patient preoperatively, while high-risk HPV were positive in the other two patients by RNAscope ISH postoperatively. None of the three cases showed MYB gene rearrangement by FISH. The mean follow-up time was 23.3 months (36, 28 and 6 months, respectively). Two patients underwent hysterectomy and radiotherapy survived without disease. One patient survived with tumor just by radiotherapy and drug therapy. Conclusions: Mixed cervical carcinoma with adenoid cystic pattern is extremely rare. It is a high-grade malignancy with poor prognosis. The tumor is associated with high-risk HPV infection, without MYB gene rearrangement, and with low PD-L1 immunoreactivity. Radical surgery combined with radiotherapy and chemotherapy is the mainstay of treatment at present.

Two new ( 1-2 ) and three known quinic acid derivatives ( 3-5 ) were isolated from the leaves of Schisandra chinensis (Turcz) Baill. The structures of the compounds were determined by spectroscopic methods, especially the NMR techniques, and also by comparison with reported data in the literature. The cytotoxicity activities of these compounds were evaluated on human tumor cell lines LN229 and three of them showed a certain activity.

Objective: To investigate the clinicopathological features and misdiagnosis factors of ALK positive large B-cell lymphoma (ALK + LBCL). Methods: The clinicopathological data of 3 patients with ALK + LBCL in the Department of Pathology, the Affiliated Hospital of Xuzhou Medical University from 2010 to 2021 were collected retrospectively. Immunohistochemistry (IHC) was used for immunophenotyping, in-situ hybridization (ISH) for EBV-encoded RNA (EBER) detection, in-situ fluorescence hybridization (FISH, break-apart probes) for ALK, MYC, and CCND1 translocations. Next-generation sequencing (NGS) was used for the detection of gene fusions and mutations. And clinicopathological features and prognosis of patients were analyzed. Results: Among the 3 ALK + LBCL patients, there were 2 males and 1 female, aged 42, 59, and 39 years, respectively, none of which presented with B symptoms. Case 1 showed systemic lymphadenopathy with elevated serum EBV DNA loading, while cases 2 and 3 presented with extranodal lesions in the nasal and hard palate, respectively. Bone marrow biopsies were performed in cases 1 and 3, and neither showed involvement. Case 1 was at clinical stage Ⅲ while both cases 2 and 3 were at stage Ⅰ, and IPI score ranged 0-1 in all cases. The morphology of these cases was similar. The architecture was effaced by sheets of cohesive large cells growing in extensive infiltration and intra-sinus growth pattern. The neoplastic cells showed immunoblastic or plasmablastic morphology, and large anaplastic cells were easily found. The tumor cells expressed ALK protein cytoplasmically in almost all cells, with ALK gene translocations detected by FISH. Common B-cell and T-cell markers, including CD20, PAX5, CD19, CD2, CD3, CD5, CD7, CD43, CD56, and bcl-2, were negative, while plasmacytic differentiation markers, including CD138, CD38, and MUM1, were positive; CD22, BOB1 and OCT2 were variably expressed. CD10 was strongly expressed only in case 3. All cases were negative for bcl-6 but positive for CD4, perforin, CD30 (partial cells), pSTAT3 (diffusely), and MYC (40%-50%). The Ki-67 index was ranged 60%-70%. MYC translocation was not detected in any case by FISH. In case 1, EBER was strongly positive in>90% of tumor cells. Case 3 was diffusely positive for cyclin D1 but negative for SOX11 expression and CCND1 translocation. All cases harbored ALK fusion genes detected by NGS. In case 1, the fusion partner was TFG, which had not been reported in DLBCL, while in the other 2 cases, ALK fused with the CTCL gene, which was commonly seen in ALK + LBCL. Cases 1 and 3 were treated with ECHOP-based chemotherapy for six cycles and were followed up for 70 and 27 months, respectively, and both achieved complete remission. Conclusions: ALK + LBCL cases with diffuse EBER-positivity reported in this study show TGF as a new fusion partner of ALK in DLBCL, together with cyclin D1 expression. These rare cases are easily confused with EBV positive diffuse large B-cell lymphoma, not otherwise specified (EBV + DLBCL, NOS), cyclin D1 positive diffuse large B-cell lymphoma (cyclin D1 + DLBCL) and ALK positive anaplastic large cell lymphoma (ALK + ALCL), resulting in misdiagnosis. Being aware of these rare phenotypes is essential for pathologists to diagnose ALK+LBCL and guide appropriate treatment accurately.

Synopsis: NF-κB signaling has been reported to play a key regulatory role in the pathogenesis of Alzheimer's disease (AD). The purpose of this study is to investigate the effects of ginkgolide on cell viability in an AD cellular model involving an APP/PS1 double gene-transfected HEK293 cell line (APP/PS1-HEK293) and further explore the mechanisms of action related to NF-κB signaling. The optimal time point and concentration of ginkgolide for cell proliferation were screened using a cell counting kit-8 assay. Based on the results, an in vitro study was performed by co-culture of APP/PS1-HEK293 with different dosages of ginkgolide, followed by an enzyme-linked immunosorbent assay to measure the levels of supernatant tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, as well as western blotting and real-time polymerase chain reaction to detect intracellular protein and mRNA expression of NF-κB p65, IκBa, Bcl-2, and Bax. APP/PS1-HEK293 cells exhibited the highest cell viability at a concentration of 100 µg/ml after 48 h of treatment with ginkgolide. The supernatant levels of TNF-α, IL-1β, and IL-6 in the high-dosage ginkgolide-treated groups were lower than those in the control group. Compared with the control group, there were decreased intracellular protein and mRNA expression of NF-κB p65 and Bax, but increased protein and mRNA expression of IκBa in both high-dosage and low-dosage groups. Ginkgolide may enhance cell viability, indicative of its neuroprotective effects on AD, at least partially via suppression of the NF-κB signaling pathway involving anti-apoptosis and anti-inflammation mechanisms. Therefore, ginkgolide might be a promising therapeutic agent against AD., (© 2022. The Author(s).)

The genus Panax is a valuable natural medicinal source used worldwide that contains high levels of triterpenoid saponins with extensive pharmacological activities. In past decades, molecular biotechnology and breeding techniques have been respectively used to generate omics data and information on cultivars primarily from Panax ginseng (ginseng), Panax quinquefolium (American ginseng), and Panax notoginseng (Sanqi) to biosynthesize valuable saponins, improve product quality, and conduct cost-controlled cultivation. Although much data have been produced, there are concerns that redundant data might be generated and that relatively scattered data might be overlooked. Therefore, many scientists desire a reliable, comprehensive omics database of the Panax genus that could save time and promote integrated analysis. Therefore, to provide all-inclusive, reliable, and valuable information on the Panax genus, PanaxGDB, an open comprehensive database that integrates data on omics and information on varieties, was established. The database contains information on nearly 600 compounds from 12 Panax species, draft genomic sequences with annotations and gene expression levels, single nucleotide polymorphisms, genome-wide association analysis based on agronomic traits, globally collected germplasm information, summaries, omics data of the Panax genus, and online versatile analytic tools. The Panax genus database will be updated when new data are released to continue serving as a central portal to boost research on the biology and functions of Panax . PanaxGDB is available at: http://panaxGDB.ynau.edu.cn., 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 Lin, Hao, Lu, Dong, Li, Zhang, Yang, Xiang, Liu, Li, Zhu, Yang, Li and Yang.)

Growing evidence indicates that vulnerable carotid plaque rupture is an important cause of stroke. However, the role of novel gemstone spectral imaging (GSI) in the assessment of vulnerable carotid plaques has remained to be sufficiently explored. Therefore, the aim of the present study was to provide a comprehensive evaluation of carotid atherosclerotic plaques using both GSI imaging biomarkers and serological biomarkers, and further explore their possible roles in the atherogenic process. The present study analyzed GSI data, including calcium content of carotid atherosclerotic plaques and spectral curve slope, as well as serum high-sensitivity C-reactive protein (Hs-CRP) and monocyte chemotactic protein-1 (MCP-1) levels in patients with a carotid atherosclerotic plaque using GSI-computed tomographic angiography and immunoturbidimetry. Patients with unstable plaque exhibited a significantly lower calcium content and higher spectral curve slope than those of the stable plaque group. In addition, patients with unstable plaque exhibited an increase in Hs-CRP and MCP-1 levels compared with those of the stable plaque and normal control groups. The alteration in GSI calcium content and spectral curve slope reflects a close link between calcification and plaque instability, while aberrant Hs-CRP and MCP-1 expression are involved in the formation or development of vulnerable plaques. Taken together, the present results strongly support the feasibility of using these serological and newly identified imaging parameters as multiple potential biomarkers relevant to plaque vulnerability or stroke progression., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Fan et al.)