N6-methyladenosine modification of circMARK2 enhances cytoplasmic export and stabilizes LIN28B, contributing to the progression of Wilms tumor.

BACKGROUND: The potential involvement of circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification in the progression of Wilms tumor (WT) has not been fully elucidated. This study investigates the regulatory mechanisms and clinical significance of m6A-modified circMARK2 and its role in WT progression. METHODS: We identified dysregulated circRNAs through deep sequencing and validated their expression by qRT-PCR in WT tissues. The biological functions of circMARK2 were assessed using clone formation, transwell migration, and orthotopic animal models. To dissect the underlying mechanisms, we employed RNA immunoprecipitation, RNA pull-down, dual-luciferase reporter assays, Western blotting, and immunofluorescence and immunohistochemical staining. RESULTS: CircMARK2, upregulated in WT tissues, was found to be m6A-modified and promoted cytoplasmic export. It facilitated WT progression by stabilizing LIN28B mRNA through the circMARK2/IGF2BP2 interaction. In vitro and in vivo studies demonstrated that circMARK2 enhances the malignant behavior of WT cells. Clinically, higher circMARK2 levels in tumor tissues of WT patients were linked to increased tumor aggressiveness and reduced survival rates. CONCLUSIONS: Our study provides the first comprehensive evidence that m6A-modified circMARK2 contributes to WT progression by enhancing LIN28B mRNA stability, promoting cellular aggressiveness. CircMARK2 emerges as a potential biomarker for prognosis and a promising target for therapeutic intervention in WT, underscoring the clinical relevance of m6A modification in pediatric renal cancer.

CircACTR2 promotes bladder cancer progression through IKBKB-mediated NF-κB signaling pathway activation.

Background: Circular RNAs (circRNAs) have significant roles in tumor progression. The role of circRNA derived from ARP2 actin-related protein 2 homolog (circACTR2) has been reported in various human diseases. However, the functions and regulatory mechanisms of circACTR2 in Bladder Cancer (BCa) remain unknown. Objectives: This study aims to explore the biological role and regulatory mechanism of circACTR2 in BCa. Methods: We analyzed the effects of circACTR2 on BCa through bioinformatics analyses, RT-qPCR, and cell function assays. Results: We observed the upregulation of circACTR2 in BCa tissues and validated its circular structure. Loss-of-function assays demonstrated that silencing circACTR2 suppressed the proliferation, invasion, and migration of BCa cells. Mechanistic investigation revealed that circACTR2 sponges miR-219a-2-3p to elevate the expression of the inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB). This induced upregulation of IKKß protein promoted the nuclear translocation of p65, thereby activating the NF-κB signaling pathway. Conclusions: Our findings indicate that circACTR2 promotes BCa cell proliferation, migration, and invasion by activating the NF-κB signaling pathway via the miR-219a-2-3p/IKBKB axis, potentially unveiling a new therapeutic target for BCa.

Radiomic analysis based on magnetic resonance imaging for the prediction of VEGF expression in hepatocellular carcinoma patients.

OBJECTIVE: The purpose of this study was to investigate the ability of radiomic characteristics of magnetic resonance images to predict vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) patients. METHODS: One hundred and twenty-four patients with HCC who underwent fat-suppressed T2-weighted imaging (FS-T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) one week before surgical resection were enrolled in this retrospective study. Immunohistochemical analysis was used to evaluate the expression level of VEGF. Radiomic features were extracted from the axial FS-T2WI, DCE-MRI (arterial phase and portal venous phase) images of axial MRI. Least absolute shrinkage and selection operator (LASSO) and stepwise regression analyses were performed to select the best radiomic features. Multivariate logistic regression models were constructed and validated using tenfold cross-validation. Receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA) were employed to evaluate these models. RESULTS: Our results show that there were 94 patients with high VEGF expression and 30 patients with low VEGF expression among the 124 HCC patients. The FS-T2WI, DCE-MRI and combined MRI radiomics models had AUCs of 0.8713, 0.7819, and 0.9191, respectively. There was no significant difference in the AUC between the FS-T2WI radiomics model and the DCE-MRI radiomics model (p > 0.05), but the AUC for the combined model was significantly greater than the AUCs for the other two models (p < 0.05) according to the DeLong test. The combined model had the greatest net benefit according to the DCA results. CONCLUSION: The radiomic model based on multisequence MR images has the potential to predict VEGF expression in HCC patients. The combined model showed the best performance.

Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104).

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8+ regulatory T (Treg)hi/CXCL13+ exhausted T (Tex)lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.

Study on the microbial diversity of ear canal secretions from patients with otomycosis.

Otomycosis is caused by fungi, which usually cause discharge and additional discomfort. The highest incidence of otomycosis occurs in summer. To better treat this disease, it is necessary to study the microbial diversity of otomycosis secretions. In this regard, this study used high-throughput sequencing technology to determine the microbial diversity of the ear canal secretions of six typical patients with otomycosis in Wuhan via internal transcribed spacer (ITS) and 16S rRNA analyses and proposed a reasonable clinical treatment plan. Six patients with otomycosis in the Department of Otorhinolaryngology, Hubei Third People's Hospital Affiliated with Jianghan University, were selected from June 2022 to August 2022. The results showed that Staphylococcus spp. (average abundance 29.05%) was the dominant bacteria and Aspergillus spp. (average abundance 90.68%) was the dominant fungus involved in otomycosis secretion. Aspergillus spp. can cause inflammation of the external auditory canal combined with bacterial infections such as Staphylococcus spp., which can cause discharge in the ear canal. High-throughput sequencing provides comprehensive information on the microbial community involved in otomycosis discharge and will aid in evaluating the efficacy of clinical treatment and medication.

Osiris17 is essential for stable integrin localization and function during insect wing epithelia remodeling.

The dynamic adhesion between cells and their extracellular matrix is essential for the development and function of organs. During insect wing development, two epithelial sheets contact each other at their basal sites through the interaction of ßPS integrins with the extracellular matrix. We report that Osiris17 contributes to the maintenance of ßPS integrins localization and function in developing wing of Drosophila and locust. In flies with reduced Osiris17 expression the epithelia sheets fail to maintain the integrity of basal cytoplasmic junctional bridges and basal adhesion. In contrast to the continuous basal integrin localization in control wings, this localization is disrupted during late stages of wing development in Osiris17 depleted flies. In addition, the subcellular localization revealed that Osiris17 co-localizes with the endosomal markers Rab5 and Rab11. This observation suggests an involvement of Osiris17 in endosomal recycling of integrins. Indeed, Osiris17 depletion reduced the numbers of Rab5 and Rab11 positive endosomes. Moreover, overexpression of Osiris17 increased co-localization of Rab5 and ßPS integrins and partially rescued the detachment phenotype in flies with reduced ßPS integrins. Taken together, our data suggest that Osiris17 is an endosome related protein that contributes to epithelial remodeling and morphogenesis by assisting basal integrins localization in insects.

Melatonin alleviates oxidative stress-induced injury to nucleus pulposus-derived mesenchymal stem cells through activating PI3K/Akt pathway.

Background: The changes in the microenvironment of degenerative intervertebral discs cause oxidative stress injury and excessive apoptosis of intervertebral disc endogenous stem cells. The purpose of this study was to explore the possible mechanism of the protective effect of melatonin on oxidative stress injury in NPMSCs induced by H2O2. Methods: The Cell Counting Kit-8 assay was used to evaluate the cytotoxicity of hydrogen peroxide and the protective effects of melatonin. ROS content was detected by 2'7'-dichlorofluorescin diacetate (DCFH-DA). Mitochondrial membrane potential (MMP) was detected by the JC-1assay. Transferase mediated d-UTP Nick end labeling (TUNEL) and Annexin V/PI double staining were used to determine the apoptosis rate. Additionally, apoptosis-associated proteins and PI3K/Akt signaling pathway-related proteins were evaluated by immunofluorescence, immunoblotting and PCR. ECMs were evaluated by RT‒PCR and immunofluorescence. In vivo, X-ray, Magnetic resonance imaging (MRI) and Histological analyses were used to evaluate the protective effect of melatonin. Results: Melatonin had an obvious protective effect on NPMSCs treated with 0-10 µM melatonin for 24 h. In addition, melatonin also had obvious protective effects on mitochondrial dysfunction, decreased membrane potential and cell senescence induced by H2O2. More importantly, melatonin could significantly reduce the apoptosis of nucleus pulposus mesenchymal stem cells induced by H2O2 by regulating the expression of apoptosis-related proteins and decreasing the rate of apoptosis. After treatment with melatonin, the PI3K/Akt pathway was significantly activated in nucleus pulposus mesenchymal stem cells, while the protective effect was significantly weakened after PI3K-IN-1 treatment. In vivo, the results of X-ray, MRI and histological analyses showed that therapy with melatonin could partially reduce the degree of intervertebral disc degeneration. Conclusion: Our research demonstrated that melatonin can effectively alleviate the excessive apoptosis and mitochondrial dysfunction of nucleus pulposus mesenchymal stem cells induced by oxidative stress via the PI3K/Akt pathway, which provides a novel idea for the therapy of intervertebral disc degeneration. The translational potential of this article: This study indicates that melatonin can effectively alleviate the excessive apoptosis and mitochondrial dysfunction of NPMSCs through activating the PI3K/Akt pathway. Melatonin might serve as a promising candidate for the prevention and treatment of Intervertebral disc degeneration disease (IVDD) in the future.

Thromboelastography (TEG) parameters as potential predictors of malignancy and tumor progression in colorectal cancer.

PURPOSE: The purpose of this study was to investigate the use of thromboelastography (TEG) in patients with colorectal cancer and to examine whether the TEG parameters can be used as potential markers for disease screening and prediction of disease severity. METHODS: One-hundred fifteen healthy controls (HC), 43 patients with benign adenoma (BA), and 387 patients with colorectal cancers (CRC) were included in the study. TEG parameters (reaction time, R; clot kinetics, K; alpha angle, α-angle; maximum amplitude, MA), conventional laboratory parameters, and clinical information were collected and analyzed among the HC, BA, and CRC groups. Receiver operating characteristics (ROC) were used for differential analysis. The correlation between TEG parameters and pathological information of CRC (differentiation degree, vaso-nerve infiltration, TNM stage) was analyzed. The differences in TEG parameters at different stages of disease and pre-/post operation were compared. RESULTS: Shorter K and higher α-angle/MA were found in patients with CRC compared with HC and BA (P < 0.001). TEG parameters demonstrated moderate diagnostic value (distinguish CRC from HC + BA: K-AUC = 0.693, α-angle-AUC = 0.687, MA-AUC = 0.700) in CRC but did not outperform traditional laboratory parameters. TEG hypercoagulability was closely associated with tumor markers (carcinoma embryonic antigen and carbohydrate antigen 19-9) and pathological information (differentiation degree, vaso-nerve infiltration, and TNM stage) (P < 0.05). Trend analysis showed that K decreased, but α-angle/MA increased gradually as the tumor progressed (P < 0.001). K- and α-angle showed slightly better sensitivity in predicting advanced tumors compared to traditional laboratory parameters. In CRC patients, 3-6 months after tumor resection, K [from 1.8 (1.5, 2.3) to 1.9 (1.6, 2.6)], α-angle [from 65.3 (59.0, 68.6) to 63.7 (56.6, 68.5)], and MA [from 61.0 (58.2, 66.0) to 58.9 (55.8, 61.3)] exhibited modest improvements compared to their preoperative values (P < 0.05). CONCLUSION: TEG parameters possess moderate diagnostic value in CRC diagnosis and predicting advanced tumors, and they are closely linked to surgical interventions. Although TEG parameters do not significantly outperform traditional laboratory parameters, they still hold promise as potential alternative indicators in CRC patients.

A meta-analysis: single or double dartos flap layer in tubularized incised plate urethroplasty to prevent urethrocutaneous fistula?

Backgrounds: Urethrocutaneous fistula is one of the most common complications after urethroplasty. This meta-analysis aims to evaluate the superiority of double dartos flap to single dartos flap in preventing fistula during tubularized incised plate urethroplasty (TIPU), which is one of the most frequently used operations for hypospadias. Methods: We extracted clinical trials under the following included criteria: (1) children with TIPU; (2) a comparison of single and double flap layer; and (3) record of complications with the following excluded criteria: (1) non-comparison and (2) lack of data. Finally, 13 studies from PubMed, Cochrane Library, Scopus, and Embase have been investigated, with a total of 1,185 patients from 2005 to 2022. The quality assessment was conducted according to the Cochrane handbook and the Newcastle-Ottawa scale. A mixed-effect model was utilized to weigh the risk of fistula, phallic rotation, meatal stenosis, and wound dehiscence by the Review Manager V.5.4 software. Results: The double dartos flap layer group excels in descending the risk of postoperative fistula [odds ratio (OR) = 9.56; 95% confidence interval (CI) (4.76, 19.22); P < 0.00001] and phallic rotation [OR = 31.26; 95% CI (9.60, 101.84); P < 0.00001], while there are no differences in the rate of meatal stenosis [OR = 1.49; 95% CI (0.73, 2.70); P = 0.31] and wound dehiscence [OR = 2.30; 95% CI (0.80, 6.63); P = 0.12]. Conclusions: The routine utility of a double dartos flap layer is recommended as a potential treatment during the tubularized incised plate urethroplasty. Systematic Review Registration: identifier PROSPERO CRD42022366294.

A meta-analysis: retrograde intrarenal surgery vs. percutaneous nephrolithotomy in children.

Backgrounds: The increasing prevalence of pediatric kidney stones worldwide makes minimally invasive lithotripsy like retrograde intrarenal surgery (RIRS) and percutaneous Nephrolithotomy (PCNL) more prevalent. However, their safety and efficacy are controversial. Consequently, a meta-analysis of the comparison between RIRS and PCNL is conducted. Methods: Clinical trials were selected from PubMed, EMBASE, Scopus, and Cochrane Library databases. The data extraction and study quality assessment were performed by two individuals independently. The data relating to therapeutic effects were extracted and analyzed by Review manager 5.4. Results: Thirteen studies involving 1,019 patients were included. The micro-PCNL excelled in stone-free rate (P = 0.003), postoperative fever rate (P = 0.02), and Clavien-Dindo II complications (P = 0.05). Notably, the mean age of the micro-PCNL group was younger than other groups (P = 0.0005). The operation time in mini-PCNL was longer than RIRS (P < 0.00001) but with high heterogeneity (I2 = 99%). There was no difference in Clavien-Dindo I, II, and III complications between the PCNL and the RIRS, but mini-PCNL showed a higher probability than RIRS in Clavien-Dindo I (P = 0.0008) and II complications (P = 0.007). Conclusions: Compared with RIRS, micro-PCNL could be a better therapeutic option for kidney stones in children. Of note, more parameters should be analyzed to illustrate the efficacy of different minimally invasive surgeries for pediatric kidney stones due to poor cases in our study. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, PROSPERO CRD42022323611.

Early surgical outcomes and influencing factors of high tibial osteotomy.

Objective: To investigate the influencing factors of functional recovery after high tibial osteotomy (HTO). Methods: A retrospective research was carried on 98 patients who underwent HTO between January 2018 and December 2020. In each case, the medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), femoral tibial angle (FTA), hip-knee-ankle (HKA), weight bearing line (WBL) ratio of the knee joint, opening gap, opening angle, American knee society knee score (KSS), US Hospital for Special Surgery (HSS) score, Lysholm score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were measured to determine postoperative function and influential factors of pain through logistic regression analysis. Results: The follow-up time was between 18 and 42 months after operation with an average of 27.66 ± 12.9 per month. Overall functional scores were significantly improved. The influencing factors that may affect the postoperative effect of HTO include age and preoperative WBL ratio of the knee joint (WBL%). After incorporating these two factors into the multivariate logistic regression analysis, for every 1 unit increase in the preoperative WBL%, the probability of postoperative HSS being superior is 1.06 times higher than before [Exp(ß): 1.062, 95% CI: 1.01-1.1, p = 0.018]. For every year increase in age, the probability of an excellent HSS score after surgery was 0.84 times higher than that before surgery [Exp(ß): 0.843, 95% CI: 0.718-0.989, p = 0.036]. Preoperative WBL% ≥ 14.37 was 17.4 times more likely to be rated as excellent postoperative HSS than that <14.37 [Exp(ß): 17.406, 95% CI: 1.621-186.927, p = 0.018]. Conclusion: The postoperative functional scores of the patients significantly improved. Patients with preoperative WBL% ≥ 14.37% had better function after surgery.

The effectiveness and influencing factors of the "Y" line technique in reducing the leg length discrepancy after total hip arthroplasty.

Objective: To introduce a surgical technique (the "Y" line technique) that will control leg length discrepancy (LLD) after total hip arthroplasty and to observe its effectiveness and influencing factors. Methods: According to the inclusion and exclusion criteria, a total of 350 patients were selected in this study; 134 patients in whom used the "Y" line technique was used to control lower limb length were included in Group A and 166 patients treated with freehand methods to control lower limb length were included in Group B. A total of 50 patients in whom the standard anteroposterior x-ray of bilateral hips was taken preoperatively and in whom the "Y" line technique was used during the operation were included in Group C. Results: The postoperative LLD of Group A was 4.74 mm (3.93), that of Group B was 5.85 mm (4.60), and that of Group C was 2 mm (1.00)-the difference was statistically significant (p < 0.001). There were significant statistical differences when comparisons were made between any two groups (p < 0.01). The distribution of postoperative LLD in Group A was better than that in Group B, and this factor was better in Group C than in Group A-the difference was statistically significant (p < 0.001). Severe unequal length rates of the lower extremities (LLD > 10 mm) were 5.97% (8/134) in Group A, 14.3% (24/166) in Group B, and 0% (0/50) in Group C-the difference was statistically significant (p < 0.001). There were significant differences between Group A and Group B and between Group B and Group C (p < 0.05), but there was no significant difference between Group A and Group C (p = 0.078). Conclusion: The "Y" line technique, which does not increase the operating time and patient cost, can effectively reduce postoperative LLD. Insufficient internal rotation of the healthy lower extremity and the low projection position in the preoperative anteroposterior x-ray of the bilateral hips were important factors affecting the accuracy of the "Y" line technique.

Exposure to elevated temperature affects the expression of PIWI-interacting RNAs and associated transcripts in mouse testes.

BACKGROUND: Exposure to heat waves could result in adverse effects on human health, especially in male testicles. PIWI-interacting RNA (piRNA) is a novel type of small non-coding RNA, which can notably impact mRNA turnover and preserve germline maintenance in germline cells. However, piRNA's expression status when adapting to testicular heat stress remains largely unclear. OBJECTIVES: To investigate the function and mechanisms of relevant piRNAs during testicular heat stress. MATERIALS AND METHODS: In this study, a mouse testicular heat stress model was constructed, and the testes were removed for piRNA-sequencing. Bioinformatics analysis was used to discover the differential expressed piRNAs, piRNA clusters, and enriched pathways. A cell heat stress model was constructed to validate the top five upregulated piRNAs. Proliferation and apoptosis assays were utilized to validate the function of selected piRNA. Bioinformatics prediction, western blotting, and immunohistochemistry were used to illustrate the downstream mechanisms. RESULTS: Through the bioinformatics analysis, we identified the differential expression profile and enriched pathways of piRNAs and piRNA clusters during testicular hyperthermia. Besides, piR-020492 was proved to be upregulated in heat stress mouse testes and a germ cell model. A series of in vitro assays illustrated that an overexpression of piR-020492 could restrain the proliferation and promote the apoptosis of mouse germ cells. Kyoto Encyclopedia of Genes and Genomes analysis of piRNA-generating genes in the testicular heat stress model and piR-020492 targeting genes showed that the overlap pathways are adenosine monophosphate-activated protein kinase (AMPK) and insulin pathways. Validation experiments demonstrated that the key genes of AMPK and insulin pathway exhibit differential expression after an overexpression of piR-020492 or testicular heat stress. DISCUSSION AND CONCLUSION: In conclusion, our findings revealed the expression profile of piRNAs in testicular heat stress and illustrated the function and mechanisms of piR-020492 in germ cells, which could provide novel insights into the mechanism of hyperthermia-induced testicular injury.

Correlation between rhizosphere environment and content of medicinal components of Arnebia euchroma / 中国中药杂志

This study aimed to explore the correlation between rhizosphere soil microorganisms of wild Arnebia euchroma and the content of medicinal components to provide guidance for the selection of the ecological planting base. The total DNA of rhizosphere soil microorganisms of wild A. euchroma was extracted, and the microbial community structure of rhizosphere soil microorganisms was analyzed by IlluminaMiseq high-throughput sequencing technology. The content of total hydroxynaphthoquinone pigment and β,β'-dimethylacrylalkannin in medicinal materials was determined by high-performance liquid chromatography(HPLC). The physicochemical pro-perties of rhizosphere soil of wild A. euchroma in main producing areas were determined, and the correlation of soil microbial abundance with index component content and soil physicochemical properties was analyzed by SPSS software. The results showed that the species composition of rhizosphere fungi and bacteria in A. euchroma from different habitats was similar at the phylum and genus levels, but their relative abundance, richness index(Chao1), and community diversity(Simpson) index were different. Correlation analysis showed that the content of available phosphorus in soil was positively correlated with the content of total hydroxynaphthoquinone pigment and β,β'-dimethylacrylalkannin, and the abundance of five fungal genera such as Solicoccozyma and six bacterial genera such as Pseudo-nocardia and Bradyrhizobium was positively correlated with the content of medicinal components in medicinal materials. The abundance of Bradyrhizobium was significantly positively correlated with the content of β,β'-dimethylacrylalkanin. The abundance of fungi such as Archaeorhizomyces was significantly positively correlated with the content of available phosphorus in rhizosphere soil, and Bradyrhizobium was significantly negatively correlated with soil pH. Therefore, the abundance of fungi and bacteria in the rhizosphere of A. euchroma has a certain correlation with the medicinal components and the physicochemical properties of the rhizosphere soil, which can provide a scientific basis for the selection of ecological planting bases in the later stage.

Advances in colonic manometry in adults with colonic motility disorders / 中华胃肠外科杂志

In recent years, colonic manometry has been gradually introduced into clinical practice. It helps clinicians to gain a better understanding of the physiology and pathophysiology of colonic contractile activity in healthy adults and patients with colonic dysfunction. More and more patterns of colonic motility are being discovered with the help of colonic manometry. However, the clinical significance of these findings still needs to be further investigated. This review enhances our understanding of colonic motility and the current state of development and application of colonic manometry, as well as the limitations, future directions and potential of the technique in assessing the impact of treatment on colonic motility patterns, by analyzing and summarizing the literature related to colonic manometry.

Clinical features of children with febrile seizures caused by Omicron variant infection / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with febrile seizures after Omicron variant infection.@*METHODS@#A retrospective analysis was performed on the clinical data of children with febrile seizures after Omicron variant infection who were admitted to the Department of Neurology, Children's Hospital Affiliated to the Capital Institute of Pediatrics, from December 1 to 31, 2022 (during the epidemic of Omicron variant; Omicron group), and the children with febrile seizures (without Omicron variant infection) who were admitted from December 1 to 31, in 2021 were included as the non-Omicron group. Clinical features were compared between the two groups.@*RESULTS@#There were 381 children in the Omicron group (250 boys and 131 girls), with a mean age of (3.2±2.4) years. There were 112 children in the non-Omicron group (72 boys and 40 girls), with a mean age of (3.5±1.8) years. The number of children in the Omicron group was 3.4 times that in the non-Omicron group. The proportion of children in two age groups, aged 1 to <2 years and 6-10.83 years, in the Omicron group was higher than that in the non-Omicron group, while the proportion of children in two age groups, aged 4 to <5 years and 5 to <6 years, was lower in the Omicron group than that in the non-Omicron group (P<0.05).The Omicron group had a significantly higher proportion of children with cluster seizures and status convulsion than the non-Omicron group (P<0.05). Among the children with recurrence of febrile seizures, the proportion of children aged 6-10.83 years in the Omicron group was higher than that in the non-Omicron group, while the proportion of children aged 3 years, 4 years, and 5 years in the Omicron group was lower than that in the non-Omicron group (P<0.05).@*CONCLUSIONS@#Children with febrile seizures after Omicron variant infection tend to have a wider age range, with an increase in the proportion of children with cluster seizures and status convulsion during the course of fever.

Effect and Mechanism of Zuojinwan on DSS-induced Ulcerative Colitis / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of Zuojinwan （ZJW） in the treatment of ulcerative colitis （UC） through network pharmacology and experimental validation. MethodUsing network pharmacology and molecular docking， the active components and potential mechanism of ZJW in treating UC were preliminarily identified. Forty-eight male C57BL/6J mice were randomly divided into a normal group， a model group， a sulfasalazine group （300 mg·kg-1）， and low-， medium-， and high-dose ZJW groups （1.82， 3.64， 7.28 g·kg-1）. The UC model was induced by dextran sulfate sodium （DSS）， and oral administration of drugs began on the third day of modeling， lasting for 7 days. The general condition of mice was observed daily， and the disease activity index （DAI） was evaluated. Hematoxylin-eosin （HE） staining was performed to observe histopathological changes in colon tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， and IL-10 in mouse serum. The molecular mechanism was validated using Western blot. ResultNetwork pharmacology predicted that the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway might be a key pathway in the regulation of UC by ZJW. Molecular docking results showed good binding ability between the key components of ZJW and core targets. Animal experiment results showed that compared with the normal group， the model group had shortened colon length （P<0.01）， increased DAI scores， spleen index， colon tissue pathology scores， and levels of TNF-α and IL-6 in serum （P<0.05， P<0.01）， increased PI3K， phosphorylated Akt （p-Akt）， and B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax） expression in colon tissue （P<0.05， P<0.01）， and decreased serum IL-10 levels and colon tissue Bcl-2 protein expression （P<0.01）. Compared with the model group， the ZJW groups showed significant improvement in UC symptoms， relieved colon tissue pathological damage， downregulated levels of inflammatory cytokines TNF-α and IL-6 in serum （P<0.01）， inhibited expression of PI3K， p-Akt， and Bax proteins in colon tissue （P<0.05， P<0.01）， and increased serum IL-10 levels and colon tissue Bcl-2 protein expression （P<0.01）， with the high-dose group showing the best effect. ConclusionZJW effectively alleviates DSS-induced UC， and its mechanism may be related to the inhibition of the PI3K/Akt signaling pathway and regulation of apoptosis-related protein expression.

Ameliorative Effect and Mechanism of Qingwen Baiduyin on Lipopolysaccharide-induced Acute Lung Injury / 中国实验方剂学杂志

To investigate the therapeutic effect and mechanism of Qingwen Baiduyin on acute lung injury （ALI） in mice induced by lipopolysaccharide （LPS）. MethodA total of 144 C57BL/6 mice were randomly divided into the following groups： a normal group， a model group （LPS， 5 mg·kg-1）， a dexamethasone group （5 mg·kg-1）， and low-， medium-， and high-dose Qingwen Baiduyin groups （14.105， 28.21， 56.42 g·kg-1）. The mice were treated once daily for 5 days. One hour after the final administration， the ALI model was established by intratracheal instillation of LPS， and samples were collected at 6 h and 24 h after modeling. The arterial blood gas index of mice was analyzed. The total protein content， total cell count， Evans blue dye （EBD） content， and lung tissue wet-to-dry weight ratio （W/D） of bronchoalveolar lavage fluid （BALF） were measured. Hematoxylin-eosin （HE） staining was performed to assess the pathological changes in mouse lung tissue. Western blot was used to detect the expression levels of key proteins in the Janus kinase 1/signal transducer and activator of transcription 1/interferon regulatory factor 1 （JAK1/STAT1/IRF1） signaling pathway in lung tissue. ResultCompared with the normal group， the model group showed reduced arterial oxygen pressure （pO2）， oxygen saturation （SO2）， and lung tissue W/D （P<0.05， P<0.01）， increased carbon dioxide pressure （pCO2）， total protein content， total cell count， EBD content， interferon-γ （IFN-γ）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， chemokine CXC ligand 1 （CXCL1）， chemokine CXC ligand 2 （CXCL2）， chemokine CXC ligand 9 （CXCL9）， and chemokine CXC ligand 10 （CXCL10） content （P<0.05， P<0.01）， thickening of the alveolar walls， fusion of alveolar cavities， and infiltration of inflammatory cells in lung tissue， increased proportion of M1 macrophage polarization and lung cell apoptosis （P<0.05）， and increased protein expression levels of JAK1， phosphorylated JAK1 （p-JAK1）， inducible nitric oxide synthase （iNOS）， STAT1， phosphorylated STAT1 （p-STAT1）， IRF1， gasdermin D （GSDMD）， and mixed lineage kinase domain-like protein （MLKL） （P<0.05， P<0.01）. Compared with the model group， Qingwen Baiduyin significantly increased pO2， SO2， and lung tissue W/D （P<0.05， P<0.01）， improved the pathological changes in lung tissue， and reduced pCO2， total protein content， total cell count， EBD content， IFN-γ， TNF-α， IL-1β， CXCL1， CXCL2， CXCL9， and CXCL10 content， proportion of M1 macrophage polarization， and protein expression levels of JAK1， p-JAK1， iNOS， STAT1， p-STAT1， IRF1， GSDMD， and MLKL （P<0.05， P<0.01）. ConclusionQingwen Baiduyin can improve the lung inflammatory response and reduce lung cell apoptosis in mice with ALI by inhibiting the JAK1/STAT1/IRF1 signaling pathway， thereby exerting a lung-protective effect.

Neurovascular coupling and central nervous system diseases / 中国药理学通报

Neurovascular coupling is the function of regulating blood flow of the central nervous system at the level of neurovascular units. The central nervous system diseases related to neurovascular coupling mainly include cerebrovascular diseases such as chronic cerebral ischemia and neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease and Lewy body dementia. The main mechanism of neurovascular coupling dysfunction leading to the above diseases is cerebrovascular dysfunction or loss,which leads to serious damage to neuronal ischemia and affects its function. Therefore,this paper reviews the research status of neurovascular coupling and its related central nervous system diseases,in order to guide the follow-up research. The purpose of this paper is to provide a basis for the prevention,relief and treatment of central nervous system diseases related to neurovascular coupling through the mechanism of neurovascular coupling.

Mechanism of antidepressant effect of Ansheng Buxin Liuwei pills based on network pharmacology / 中国药理学通报

Aim To apply network pharmacology, molecular docking, and in vitro experimental techniques to predict as well as verify the antidepressant pharmacological mechanisms of Mengyao Anshen Buxin Liuwei pills. Methods TCMSP database and literature mining were used to obtain the active ingredients of Anshen Buxin six flavor pills , Swiss Target Prediction was applied to predict the ingredient related target information, and Cytoscape was employed to construct a medicinal herb ingredient target network. Depression targets were retrieved through GeneCards , Drugbank , OMIM and other databases. STRING database was used to obtain protein interaction relationship network information. DAVID database was used for GO biological process enrichment analysis and KEGG signaling pathway enrichment analysis. Autodock vina software was applied for molecular docking validation. In vitro injury model was established in BV2 microglial cells, cell viability was assessed by CCK-8 assay, and the mRNA expression of relevant core targets was assessed by qPCR. Results A total of 34 active components of Anshen Buxin Liuwei pills were screened, involving 140 potential targets and 59 core targets, involving 99 signaling pathways. Molecular docking results showed that betulinic acid, stigmasterol p-stiosterol 10 active components such as sitosterol and quercetin had good binding ability with AKT1, APP, ALB, MAPK3, VE GFA and MAPK 1 targets. The re suits in vitro showed that the activity of BV2 cells increased significantly compared with the model group. Anshen Buxin Liuwei pills could regulate the mRNA expression of each core target. Conclusion Anshen Buxin Liuwei pills may play an antidepressant role mainly through serotonin synaptic and other signaling pathways and related core targets.