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.

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 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.

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.

Objective:To analyze the relationship between gene polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and plasminogen activator inhibitor-1 (PAI-1) and lower limb deep venous thrombosis (DVT) after colorectal cancer surgery.Methods:The clinical data of patients with colorectal cancer who underwent surgical treatment in Zhangjiakou First Hospital from February 2020 to February 2023 were analyzed retrospectively. According to the presence or absence of lower limb DVT after surgery, the patients were divided into DVT group (20 cases) and non-DVT group (80 cases). The polymorphism of MTHFR C677T and PAI-1 promoter 4G/5G were detected by polymerase chain reaction method. The relationship between the polymorphisms of MTHFR C677T and PAI-1 promoter 4G/5G and lower limb DVT after colorectal cancer surgery was discussed by logistic regression analysis.Results:TT genotype frequency and T allele frequency of MTHFR C677T in the DVT group were higher than those in the non-DVT group: 65.00% (13/20) vs. 25.00% (20/80), 80.00% (32/40) vs. 38.75% (62/160). CC genotype frequency and C allele frequency were lower than those in the non-DVT group: 5.00% (1/20) vs. 47.50% (38/80), 20.00% (8/40) vs. 61.25% (98/160), with statistically significant differences ( P<0.05). There was no significant difference in CT genotype frequency between the two groups ( P>0.05). 4G/4G gene frequency and 4G allele frequency of PAI-1 gene in the DVT group were higher than those in the non-DVT group: 50.00% (10/20) vs. 21.25% (17/80), 67.50% (27/40) vs. 38.75% (62/160). 5G/5G gene frequency and 5G allele frequency were lower than those in the non-DVT group: 15.00% (3/20) vs. 43.75% (35/80), 32.50% (13/40) vs. 61.25% (98/160), with statistically significant differences ( P<0.05). There was no significant difference in 4G/5G gene frequency between the two groups ( P>0.05). The distribution frequency of TT genotype of MTHFR C677T and 4G/4G genotype of PAI-1 promoter in DVT group was higher than that in non-DVT group: 55.00% (11/20) vs. 22.50% (18/80), with a statistically significant difference ( P<0.05). Multivariate Logistic regression analysis showed that MTHFR C677T TT genotype ( OR = 1.499, 95% CI 1.201 to 1.871), PAI-1 promoter 4G/4G genotype ( OR = 1.471, 95% CI 1.170 to 1.850) and MTHFR The C677T loci TT genotype combined with the 4G/4G genotype of the PAI-1 promoter ( OR = 1.592, 95% CI 1.258 to 2.014) were risk factors for lower limb DVT after colorectal cancer surgery ( P<0.05). Conclusions:The TT genotype of MTHFR C677T site and the 4G/4G genotype of PAI-1 promoter are closely related to the formation of lower limb DVT after colorectal cancer surgery, and the risk of lower limb DVT is higher in patients with both genotype TT and 4G/4G.

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*

Neonatal hyperbilirubinaemia, clinically presenting as jaundice, is a ubiquitous and commonly a benign metabolic condition in newborn infants.It is a leading cause of hospitalization of neonates in the first week of life.Serum bilirubin has been considered as the most potent superoxide with the peroxyl radical scavenger activity.However, uncontrolled hyperbilirubinaemia or rapidly rising bilirubin can reach a neurotoxic concentration, potentially leading to central nervous system sequelae.Thus, the health status of jaundiced newborn infants is dependent on striking an appropriate balance between the protective effects of serum bilirubin and the risk of bilirubin neurotoxicity.In order to standardize the management of neonatal hyperbilirubinemia (jaundice), many countries have developed clinical practice management guidelines.This review sorted out and briefly interpreted the main contents of clinical management guidelines for neonatal hyperbilirubinemia drafted by the American Academy of Pediatrics and other countries, aiming to provide references of clinical diagnosis and treatment practice to domestic pediatrician.

Anemia and blood transfusion are common clinical problems in newborns, especially premature infants.What are the definition and influencing factors of neonatal anemia? What is the difference between anemia in preterm infants and full-term infants? What are the changes of pathophysiology and their effects on tissues and cells during neonatal anemia? What are the prevention strategies and treatment methods of neonatal anemia? Is there a uniform hemoglobin threshold for neonatal transfusion of red blood cells? What are the risks of blood transfusion? In view of the above problems, this review proposed that the definition of anemia should consider the effects of gestational age, day age, intrauterine or postnatal development status(such as growth retardation), nutrition and so on. "Physiological anemia of infancy" can occur in healthy term infants; "anemia of prematurity" can not be considered as a physiologic and benign event, which is related to the low level of endogenous erythropoietin and iatrogenic blood loss.It is emphasized that neonatal anemia(especially premature infants) is preventable and can be prevented, and prevention is more important than treatment.Neonates lack a uniform hemoglobin threshold and are at risk of blood transfusion during red blood cell transfusion.