Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

Objective To investigate the clinicopathological features,immunophenotype,diagnosis and treatment of SMARCA4(BRG1)-deficient carcinoma.Methods Clinical data of 11 patients with SMAR-CA4(BRG1)-deficient cancer were collected.The morphologic and immunohistochemical features of this tumour were summarized,and the relevant literature was reviewed.Results Among the 11 cases of SMARCA4(BRG1)-deficient carcinoma,eight were male and three were female,with median age of 60.Seven patients underwent radical resection,and four underwent traditional joint targeted chemotherapy and immunotherapy.Microscopically,the tumor cells were epithelioid,rhabdoid or spindle-shaped,with prominent eosinophilic nucleoli and frequent mitoses(>5/10 HPF).Multiple foci of necrosis were found in the tumor tissue,a large number of tumor emboli in the blood vessels and myxoid stromal degeneration.Among these cases,11 cases showed loss of SMARCA4(BRG1)expression,whereas the CK and Vim markers were expressed,SMARCB1(INI1)expression was retained,and p53 mutation was detected.The tumor cells showed high proliferation activity(Ki-67>60%),and synaptophsin was moderately positive.Three cases were mismatch repair deficient and respectively showed the loss of MLH1/PMS2,PMS2 and MSH6 expression.Conclusion The incidence of SMARCA4(BRG1)-dificient carcinoma is low.It can be easily confused with other tumors and is difficult to be diagnosed before operation,which requires confirmation by immunohistochemistry.

Objective To compare the effects of SARIMA,LSTM and EDM in predicting the incidence of HFRS in Weifang under different circumstances,and explore the best prediction model.Methods The monthly incidence of HFRS in Weifang from January 2011 to December 2017 was selected to construct the SARIMA model,univariate LSTM model,univariate EDM model,and SARIMAX model,multivariate LSTM model,and multivariate EDM model including meteorological factors.The monthly incidence from January 2018 to December 2018 was predicted,and the prediction effects of each model were compared.Results The MAPE of SARIMA model,univariate LSTM model,multivariate LSTM model,univariate EDM model,multivariate EDM model were 42.17%,48.40%,16.19%,55.00%,51.79%,respectively.Conclusion The multivariate LSTM model including meteorological factors had a good prediction effect on the incidence of HFRS in Weifang,and the prediction results could provide reference for the prevention and control of HFRS.

Objective To comprehensively analyze the epidemiological characteristics and resistance mechanisms of New Delhi metallo-β-lactamase(NDM)-positive multidrug-resistant bacteria in China.Methods Relevant literatures on NDM-positive multidrug-resistant bacteria discovered in China were searched in the CNKI and PubMed databases(publications from January 1,2017 to December 31,2023).The epidemiological analysis was conducted on the types of NDM-positive bacterial strains,their regional distribution,infection sources,resistance profiles,and transfer mechanisms.Results A total of 118 eligible articles were collected,reporting 1627 NDM-positive bacterial strains.The number of reports increased annually from 2011 to 2019,but began to decline annually from 2020 onwards.NDM-1 and NDM-5 were the most commonly reported variants.The highest number of reports came from Eastern China,followed by Central China and North China.The primary pathogens were Klebsiella pneumoniae,Escherichia coli,and Enterobacter cloacae.The age distribution of patients with NDM-positive infections showed distinct patterns,with neonates and children accounting for 27.25％and patients over 50 years old accounting for 49.57％.The majority of positive bacterial infections came from sputum(38.28％),urine(28.94％),and blood(23.28％).The main departments reporting NDM-positive bacteria were the ICU(39.93％)and pediatrics(20.14％).These resistant bacteria exhibited resistance to more than 50.00％of antibiotics,with lower resistance to colistin and tigecycline(below 30.00％).The predominant plasmid type carrying the blaNDMwas IncX3,and the insertion sequences upstream and downstream of the blaNDM showed diversity.Conclusion NDM-positive multidrug-resistant bacteria are widely prevalent across regions in China,exhibiting multidrug-resistance.This poses significant challenges to clinical antibiotic selection and necessitates the development of effective countermeasures.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Objective:To explore the diagnostic value of contrast-enhanced mammography (CEM) and MRI in differentiating benign and malignant breast lesions based on the 2013 breast imaging reporting and data system (BI-RADS) lexicon and the supplement on CEM.Methods:The clinical and imaging data of 83 patients with breast lesions from March 2019 to April 2022 in the Third Affiliated Hospital of Soochow University were retrospectively analyzed. Totally 100 breast lesions from 83 female patients aged 28 to 78 (49±14) years, were divided into benign lesions (50 lesions) and malignant lesions (50 lesions) according to the pathological results. The t-test, χ 2 test and Fisher′s exact test were used to compare the differences of clinical and imaging features between benign and malignant lesions, and these imaging features which had statistical differences were established CEM and MRI models by multivariate logistic regression analysis respectively. The receiver operating characteristic curves and the area under the curve (AUC) were used to assess the diagnostic efficacy of two models in differentiating benign and malignant breast lesions. Using the DeLong test compared the AUC. Results:Multivariate logistic regression analysis showed that associated features (OR=9.075,95%CI 1.430-57.570, P=0.019), lesion conspicuity (OR=6.180,95%CI 2.608-14.646, P<0.001), mass margin (OR=2.193,95%CI 1.405-3.422, P=0.001) and calcification distribution (OR=2.147,95%CI 1.157-3.986, P=0.015) were independent predictors of differentiating benign and malignant breast lesions in CEM, and then the predictive model of CEM was constructed. Time-signal intensity curve (OR=9.230, 95%CI 3.178-26.805, P<0.001), associated features (OR=5.289,95%CI 1.343-20.831, P=0.017) and mass margin (OR=2.192,95%CI 1.336-3.597, P=0.002) were independent predictors of differentiating benign and malignant breast lesions in MRI, and the predictive model of MRI was constructed. The AUC of CEM and MRI models for differentiating benign and malignant breast lesions were 0.947 and 0.930 respectively, and two models were no significant difference ( Z=0.68, P=0.494). Conclusion:The diagnostic efficacy of CEM and MRI in differentiating benign and malignant breast lesions is comparable based on the 2013 BI-RADS lexicon and the supplement on CEM.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Magnolia ; White Matter ; Brain Ischemia/metabolism* ; Oligodendroglia/metabolism*

Objective:To explore the characteristics of weekly gestational weight gain (GWG) in women with obesity and its correlation with the risk of macrosomia.Methods:Clinical data of women with singleton pregnancy and pre-pregnancy body mass index (PPBMI) ≥28 kg/m 2 were retrospectively analyzed, from January 2014 to December 2019, in Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Beijing Maternal and Child Health Care Hospital). The participants were divided into three groups based on their PPBMI: group A (28-<30 kg/m 2), group B (30-<32 kg/m 2), and group C (≥32 kg/m 2). The study compared the characteristics of GWG among the three groups, explored the correlation between the weekly weight gain during each gestational stage and the risk of macrosomia, and discussed the impacts of the GWG pattern in women with different PPBMI on the risk of macrosomia. Chi-square (or Fisher's exact), Kruskal-Wallis, and Mann-Whitney U tests were performed for statistical analysis. Multivariate logistic regression was used to analyze the impact of weekly weight gain in specific gestational stages on macrosomia. Results:(1) A total of 2 046 participants were included in the study, with 982 in group A, 588 in group B, and 476 in group C. For all of the 2 046 cases, the median PPBMI was 30.1 kg/m 2 (29.0-31.9 kg/m 2), GWG was 10.5 kg (7.3-14.0 kg), and neonatal birth weight was 3 520 g (3 215-3 816 g) with 60 (2.9%) ≥4 500 g, and the biggest baby weighed 5 580 g. Out of the births analyzed, macrosomia occurred in 318 cases (15.5%). (2) Among the three groups (A, B and C), the differences in maternal age [32.0 years (29.0-35.0 years), 32.0 years (29.0-35.0 years) and 32.0 years (29.0-34.0 years), H=6.58] and women with a history of type 2 diabetes mellitus [0.9% (9/982), 0.3% (2/588) and 1.9% (9/476), χ2=6.61] were statistically significant (all P<0.05). (3) The weekly weight gain in each group exhibited a gradual upward trend before 20-24 weeks, reached a plateau at 24-32 weeks, peaked at 32-36 weeks, and subsequently declined. The weekly weight gain of group A in the pre-pregnancy to 14 weeks [0.14 kg/week (0.00-0.25 kg/week)], 14 to 20 weeks [0.25 kg/week (0.17-0.42 kg/week)], and 20 to 24 weeks [0.38 kg/week (0.25-0.63 kg/week)] were higher than those of group B [0.07 kg/week (－0.03-0.21 kg/week), 0.25 kg/week (0.10-0.42 kg/week), and 0.38 kg/week (0.22-0.60 kg/week)], respectively ( Z value was－3.73,－2.16, and－2.01, all P<0.05). Likewise, the weekly weight gain of group B in the above three stages were all higher than those of group C [0.07 kg/week (－0.10-0.21 kg/week), 0.17 kg/week (0.05-0.33 kg/week), and 0.25 kg/week (0.08-0.50 kg/week)], respectively ( Z value was－2.55,－3.28, and－3.25, all P<0.05). (4) The risk of macrosomia increased with the weekly weight gain in specific gestational stages in different PPBMI groups. In group A, the stages correlated with increased risk were 14-20 weeks [adjusted odd ratio ( aOR)=2.669, 95% CI: 1.378-5.169] and 20-24 weeks ( aOR=1.764, 95% CI: 1.143-2.723), while the stages were 20-24 weeks ( aOR=2.149, 95% CI: 1.156-3.996) and 36 weeks until delivery ( aOR=1.888, 95% CI: 1.268-2.810) in group B, and pre-pregnancy to 14 weeks ( aOR=3.515, 95% CI: 1.158-10.665) and 14-20 weeks ( aOR=3.021, 95% CI: 1.058-8.628) in group C (all P<0.05). The risk of macrosomia increased when the weekly weight gain of both risk-related stages in group A ( aOR=2.255, 95% CI: 1.029-4.940) ≥50th percentile, and group B ( aOR=4.399, 95% CI: 1.017-19.023) ≥75th percentile, and for group C ( aOR=3.404, 95% CI: 1.004-11.543) when the weekly weight gain above 25th percentile (all P<0.05). Conclusions:Weekly GWG demonstrates an observable gradual acceleration pattern in women with obesity. Therefore, clinical attention should be directed towards monitoring fluctuations in the weekly weight gain in this population, as excessive weekly weight gain before 24 gestational weeks is associated with an elevated risk of macrosomia.

Objective:To understand the genome analysis and molecular typing of foodborne Yersinia enterocolitica ( Y.e) strains in Liaocheng City of Shandong Province from 2020 to 2021. Methods:The Y.e strains were isolated from raw meat and meat products. Then we made the strain identification, drug sensitivity test, virulence gene test, pulsed-field gel electrophoresis (PFGE), and whole genome sequencing (WGS). The genome sequencing data were assembled with the microbial genome annotation package. We performed the multilocus sequence typing (MLST) and core genome multilocus sequence typing (cgMLST) and used WGS-based single nucleotide polymorphism typing (wg-SNPs) method to carry out genetic evolution analysis with 14 domestic and Y.e genomes obtained from the NCBI. Results:A total of 21 strains of Y.e were detected from 165 samples, with a detection rate of 12.73%. The 20 strains of Y.e were sequenced successfully. The 20 strains of Y.e carries a variety of drug resistance genes and virulence genes, showing multiple drug resistance. The virulence gene PCR test showed that 21 strains of Y.e having two virulence genes. Cluster analysis of PFGE, MLST, and cgMLST showed that the genomics of 21 strains was highly diverse. The genetic evolution analysis of wg-SNPs showed that 20 Y.e strains could be divided into two main evolutionary branches. Conclusions:Y.e strains isolated from raw meat in Liaocheng City carry a variety of drug resistance genes and virulence genes, and the molecular typing is highly diverse, which may cause infection risk. The molecular biological monitoring of Y.e in raw meat should be strengthened, and genome sequencing and molecular typing detection be carried out to provide the theoretical basis for foodborne illness caused by Y.e.