Objective To investigate the role and regulatory mechanism of LINC00657 in the progression of cervical cancer. Methods Bioinformatics analysis predicted potential binding sites between LINC00657 and miR-30a-5p and between miR-30a-5p and Skp2. These sites were verified by using RNA immunoprecipitation and dual-luciferase reporter experiments. LINC00657, miR-30a-5p, and Skp2 mRNA expression levels in cervical cancer tissues and cell lines were assessed by utilizing RT-qPCR. Western blot analysis was employed to examine the protein levels of Skp2 in cells and subcutaneous xenograft tumor models in nude mice. Immunohistochemistry was applied to analyze Skp2 expression in animal tissues. The cellular processes of cervical cancer cell lines were evaluated through CCK-8, scratch, and Transwell assays. Results LINC00657 and Skp2 presented binding sites for miR-30a-5p. In cervical cancer, LINC00657 and Skp2 showed high expression levels (P<0.05), whereas miR-30a-5p displayed low expression (P<0.05). Functional experiments demonstrated that linc00657 upregulates Skp2 expression, a process that is dependent on its sequestration of miR-30a-5p. Conclusion LINC00657 promoted the malignant progression of cervical cancer by upregulating Skp2 expression through specifically sequestering miR-30a-5p, thereby relieving its inhibitory effect on the target gene Skp2.

ObjectiveTo investigate the intervention effects of modified Linggui Zhugan Tang （LGZGT） on patients with obstructive sleep apnea-hypopnea syndrome （OSAHS） of the spleen deficiency and dampness obstruction with blood stasis type， reveal its possible mechanisms， and provide a theoretical basis for the clinical treatment of OSAHS with traditional Chinese medicine （TCM）. MethodsEighty OSAHS patients with spleen deficiency and dampness obstruction with blood stasis were randomly assigned to a control group and an observation group （1∶1） using a random number table， with 40 patients in each group. The control group received standard basic treatment combined with oral Doxofylline tablets， while the observation group received standard basic treatment combined with modified LGZGT. Serum levels of macrophage migration inhibitory factor （MIF）， microRNA-223 （miR-223）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of MIF， miR-223， and IL-18 were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. After two months of treatment， the total clinical efficacy， apnea-hypopnea index （AHI）， lowest nocturnal oxygen saturation （LSpO₂）， body mass index （BMI）， TCM syndrome scores， and expression levels of MIF， miR-223， and IL-18 before and after treatment were compared between the two groups. Correlations between MIF， miR-223， IL-18 and AHI and LSpO₂ were also analyzed. ResultsCompared with the control group， the observation group showed a significantly higher total clinical effective rate （P<0.01， Z=-3.49）. Within the control group， no significant changes were observed in AHI， LSpO₂， BMI， TCM syndrome scores， or MIF， miR-223， IL-18 levels and their mRNAs after treatment. In the observation group， AHI， BMI， TCM syndrome scores， and MIF and IL-18 levels and their mRNAs decreased significantly， while LSpO₂ increased significantly （P<0.01）. After treatment， compared with the control group， the observation group exhibited significantly lower AHI， BMI， TCM syndrome scores， and MIF and IL-18 levels and their mRNAs， and significantly higher LSpO₂ （P<0.01）. Correlation analysis showed that MIF and IL-18 were positively correlated with AHI （P<0.01） and negatively correlated with LSpO₂ （P<0.01）， whereas miR-223 was negatively correlated with AHI （P<0.01） and positively correlated with LSpO₂ （P<0.01）. ConclusionModified LGZGT may improve OSAHS of the spleen deficiency and dampness obstruction with blood stasis type by reducing airway inflammatory factors， alleviating airway inflammation， relieving airway edema and stenosis， and improving airway obstruction.

Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme (NAE) (E1), E2 NEDD8-conjugating enzyme (E2), and E3 NEDD8-ligase (E3). The most extensively studied substrates of neddylation are members of the cullin family, which act as scaffold components for cullin ring E3 ubiquitin ligases (CRLs). Since cullin neddylation activates CRLs, which are frequently overactive in tumors, inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies. This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions (PPIs) within the neddylation enzymatic cascade.

OBJECTIVE To explore the effect and mechanism of Zexie tang （ZXT） on reducing lipid accumulation through network pharmacology， and compare the difference of traditional decoction versus formula granules. METHODS The active components and targets of ZXT were identified using TCMSP and SwissTargetPrediction databases. GeneCards， OMIM， DisGeNET and TTD databases were used to analyze the related targets of non-alcoholic fatty liver disease （NAFLD）； protein-protein interaction network model was constructed by String database；“ ZXT-NAFLD target-pathway” network diagram was constructed by using CytoScape software； target enrichment analysis was performed by using Metascape platform. Fat accumulation model of human hepatocellular carcinoma HepG2 cells was established to observe the effects of traditional decoction and formula granules of ZXT on lipid accumulation of cells. RESULTS Alisol B， alisol C， 1-monolinolein and alisol B monoacetate were the key active components of ZXT in the treatment of NAFLD. The core targets included MDM2， MAPK1， PIK3CB， PRKCQ and MAPK14， etc. The core signaling pathways included endocrine resistance， insulin resistance and Th17 cell differentiation. Compared with model group， except for the Zexie formula granules group and Baizhu formula granules group， the absorbance values in all other administration groups were significantly decreased （P＜0.01）； the absorbance value of Baizhu traditional decoction group was significantly higher than that of ZXT traditional decoction group （P＜0.01）； the absorbance values of Zexie formula granule group and Baizhu formula granule group were significantly higher than that of ZXT formula granule group （P＜0.01）； the absorbance value of Zexie formula granule group was significantly higher than that of Zexie traditional decoction group （P＜0.01）； the absorbance value of Baizhu formula granule group was significantly higher than that of Baizhu traditional decoction group （P＜0.01）. CONCLUSIONS ZXT reduces lipid accumulation of human hepatocellular carcinoma cells through multiple components， multiple target and multiple pathways， and its traditional decoction and formula granules exhibit slightly different lipid-lowering effects.

ObjectiveTo investigate the current status and related factors of maternal influenza vaccination willingness among pregnant and postpartum women in Shanghai and Liaoning Province, China, and to explore the facilitators and barriers affecting vaccination uptake, so as to provide references for future practices in promoting maternal influenza immunization in China. MethodsA convergent mixed-methods research was conducted. From January to March 2024, a questionnaire survey was conducted among women attending prenatal and postnatal care at 7 medical institutions in Shanghai and Dalian, Liaoning Province, which aimed to assess pregnant women’s knowledge about influenza vaccine and their willingness to vaccination during pregnancy, as well as to identify the related factors. In addition, purposive sampling method was used to conduct in-depth interviews with pregnant women and perinatal healthcare service providers to explore their perspectives on influenza vaccination during pregnancy, including the reasons for their willingness or unwillingness to receive ( or recommend) the vaccine, and the relevant facilitators and barriers to vaccination. ResultsA total of 366 pregnant and postpartum women participated in the questionnaire survey, and 9.56% (35/366) of them were willing to receive the influenza vaccine during pregnancy. The results of multivariate logistic stepwise regression analyses showed that primipara (aOR=0.158, 95%CI: 0.037‒0.671, P=0.012), family members’ support for influenza vaccination during pregnancy (aOR=0.015, 95%CI: 0.003‒0.082, P<0.001) were associated with higher willingness to receive influenza vaccine during pregnancy. Absence of influenza infection during pregnancy (aOR=5.383, 95%CI: 1.801‒16.092, P<0.001), and lack of knowledge regarding influenza vaccination during pregnancy (aOR=11.294, 95%CI: 3.593‒35.496, P<0.01) were associated with lower willingness to receive influenza vaccine during pregnancy. Qualitative findings indicated that the facilitators to vaccination willingness among pregnant and postpartum women included the recommendation of healthcare service providers, adequate knowledge of influenza vaccine information and family members’ support for vaccination. Conversely, the barriers to vaccination willingness included low recommendation from the healthcare service providers, lack of knowledge about the safety of influenza vaccine during pregnancy and inadequate attention to influenza and influenza vaccine. ConclusionThe willingness to receive influenza vaccination among pregnant and postpartum women in Shanghai and Liaoning Province is relatively low. It is recommended that China should promptly improve the evidence-based system for the safety and efficacy of influenza vaccines for pregnant and postpartum women, along with an establishment of the mechanism for addressing adverse reactions. Furthermore, it is essential to enhance educational outreach to pregnant and postpartum women, their families, and healthcare service providers, thereby increasing the accessibility of information regarding influenza vaccination, which are expected to enhance the willingness of pregnant and postpartum women to receive the vaccine.

Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8(NEDD8)to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme(NAE)(E1),E2 NEDD8-conjugating enzyme(E2),and E3 NEDD8-ligase(E3).The most extensively studied substrates of neddylation are members of the cullin family,which act as scaffold components for cullin ring E3 ubiquitin ligases(CRLs).Since cullin neddylation activates CRLs,which are frequently overactive in tumors,inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies.This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions(PPIs)within the neddylation enzymatic cascade.

ObjectiveTo explore the effect of Qingre Huayu Jianpi prescription （QHJ） on colitis-associated colorectal cancer （CAC） in mice， and its related mechanism. MethodC57BL/6 mice were randomly divided into four groups including the normal， model， QHJ low-dose （QHJ-L， 10 g·kg^-1）， and QHJ high-dose （QHJ-H， 40 g·kg^-1） groups. Azoxymethane （AOM） and dextran sodium sulfate （DSS） were combined to chemically build a CAC mouse model for 14 weeks. Each drug group was given intragastrically from the 5^th week to the 14^th week， once per day. An equal volume of water was fed to the normal and model groups. The mouse survival rate， colon length， weight， and pathological alterations were assessed. The protein expressions of Wnt-3a protein signaling （Wnt3a）， β-catenin， Non-phosphor-β-catenin （Non-p-β-catenin）， and cholesterol-binding glycoproteins 133 （CD133） were detected by Western blot. The localization and expression of the cluster of differentiation （CD） 80 and CD11 antigen-like family member B （CD11b） were detected by immunohistochemistry （IHC）. The colon organoids derived from CAC mice were isolated and cultured to detect the expression of Wnt signaling pathway-related proteins. ResultThe survival rate of the CAC mice was improved by QHJ treatment and the number of colon tumors was inhibited significantly. Compared with those in the normal group， the expression levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in colon tissues in the model group were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， the levels of Wnt3a and β-catenin in the QHJ-L group were significantly decreased （P<0.01）， and the protein levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in the QHJ-H group were significantly decreased （P<0.05， P<0.01）. Meanwhile， the expression level of CD11b in the model group was significantly increased compared with that in the normal group while the CD80 level was significantly decreased （P<0.05， P<0.01）. Compared with those in the model group， CD11b in QHJ-L and QHJ-H groups was significantly decreased， and CD80 was significantly increased（P<0.05， P<0.01）. The expressions of Non-p-β-catenin and CD133 in colonic organoids of CAC model mice were significantly increased， while QHJ treatment could inhibit the expressions of Non-p-β-catenin and CD133 in colonic organoids （P<0.01）. ConclusionQHJ could inhibit the inflammation-cancer development in CAC mice， the mechanism of which might be related to regulating the microenvironment and inhibiting the over-activation of Wnt signaling.

Objective:To investigate the changes of dynamic functional brain network connectivity in patients with Parkinson disease(PD) using Hidden Markov model(HMM), and to analyze the correlation between dynamic functional parameters and clinical parameters.Methods:Forty-eight PD patients(PD group) and thirty-three healthy controls(HC group) were included from 2019 to 2023. The cognitive function was assessed using the Montreal cognitive assessment (MoCA), and motor status was assessed using the unified Parkinson's disease rating scale Ⅲ(UPDRS-Ⅲ) in PD group.HMM technique was used to analyze the dynamic functional brain network connectivity, and the dynamic higher-order index fractional occupancy(FO), switching rate(SR), and mean dwell time(MDT) were obtained. Two independent samples t-test was used to calculate the differences between groups of functional connectivity matrices in different states, and Mann-Whitney U test was used to calculate the differences between groups of dynamic higher-order indicators in different states. Spearman correlation analysis was used to calculate the correlation between dynamic higher-order parameters and clinical parameters in the PD group. Results:The HMM was used to construct 6 spatial states for all subjects.MDT was significantly higher in PD group(24.93(19.73)) in state 1 sparse junctions than that in HC group(17.63(14.80)) ( Z=-2.030, P=0.042), but significantly lower MDT was showed in PD group(6.00(3.00)) in state 5 tight junctions than that in HC group(9.75(7.70)) ( Z=-2.210, P=0.027).FO in state 3 was negatively correlated with MoCA score in PD group( r=-0.331, P=0.022).FO in state 5 was positively correlated with UPDRS-Ⅲ score in PD patients( r=0.412, P=0.004), and MDT in state 5 was positively correlated with UPDRS-Ⅲ score( r=0.448, P=0.001). Conclusion:HMM can capture the transient changes of dynamic brain network, which can provide some value for the study of dynamic brain network in patients with Parkinson disease.

Objective To comprehensively analyze the circulatory RNA-long non-coding RNA-microRNA-messenger RNA(circRNA-lncRNA-miRNA-mRNA)network in cervical cancer and construct a prognostic model.Methods Differential and key genes were ana-lyzed using bioinformatics based on data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Prognostic mRNA models were constructed based on TCGA database using univariate,Least Absolute Shrinkage and Selection Operator(LASSO),and multivariate Cox regression analyses and validated using the GEO database.The R package and Cystoscape software were used to construct a nomogram model and competing endogenous(ceRNA)network of circRNA-lncRNA-miRNA-mRNA in cervical cancer.Results A prognostic model including five mRNAs was constructed using univariate,LASSO,and multivariate Cox regression analyses,which had area under the receiver operating characteristic curve AUC values of 0.71,0.71,and 0.70 at 1,2,and 3 years,respec-tively,indicating its sensitivity and specificity in cervical cancer prognosis.Predictive results were validated using the GSE44001 dataset.The C-index of the nomogram model for this prognostic model was 0.707.In this study,a ceRNA network comprising 39 circRNAs,27 lncRNAs,12 miRNAs,and five mRNAs was constructed.Conclusion The network constructed in this study can help comprehensively elucidate the mechanism of ceRNAs in cervical cancer,and the construction of prognostic and Nomogram models can predict patient prog-nosis.

Epidermal growth factor receptor (EGFR) mutations are the most common driver genes in the development of non-small cell lung cancer (NSCLC), of which mutations in exons 18-21 are frequent, especially the loss of exon 19 and exon 21 L858R mutation are the most frequent. Other rare gene mutations are rare. Simultaneous occurrence of two or more rare EGFR mutations are extremely rare in lung cancer, and the incidence of EGFR L833V/H835L rare gene compound mutations is very low, and there is little clinical data and evidence of relevant treatment methods. Some EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are effective in treating lung cancer patients with rare gene mutations. In this article, we reported a case of NSCLC patient with a rare gene compound mutation EGFR L833V/H835L, who responded to Afatinib in combination with Anilotinib treatment well after 5 months of treatment, and computed tomography (CT) showed shrinkage of lung lesions. Meanwhile, we also compiled previously reported NSCLC patients with EGFR L833V/H835L rare gene compound mutation and summarized the characteristics of this group of patients and the effect of applying different kinds of EGFR-TKIs treatment.
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Humans ; Adenocarcinoma of Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/pathology* ; ErbB Receptors/genetics* ; Lung Neoplasms/pathology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use*