Aim To study the main active components and potential mechanism of selenshenzhi prescription a-gainst esophageal cancer by network pharmacology and in vivo and in vitro experiments.Methods The com-mon target was extracted from TCMSP,OMIM and GeneCards databases,and the PPI network was con-structed using STRING database.DAVID database was used for GO and KEGG enrichment analysis,and a network was constructed based on STRING and DAVID database for in vivo and in vitro experimental verifica-tion.Results Prediction results showed that a total of 100 active ingredients and 749 related targets were ob-tained,and 168 common targets were obtained between selenoshenzhi recipe and esophageal cancer,which were involved in the PI3K-AKT signaling pathway and proteoglycan signaling pathways in cancer.Selenshenz-hi prescription was used to conduct preliminary verifi-cation of related targets for human esophageal cancer EC9706 based on in vitro experiments.The results showed that selenshenzhi prescription could significantly inhibit the proliferation of esophageal cancer cells and induce the apoptosis of EC9706 through the expression of Bax,Bcl-2,caspase-3 and other key apoptotic pro-teins.Lastly,the core target and pathway of selensh-enzhi prescription were preliminically verified based on in vivo animal experiments on nude mice with esopha-geal cancer.The results showed that selenshenzhi pre-scription could significantly inhibit tumor proliferation,promote tumor cell apoptosis,and induce tumor apop-tosis by regulating the expression of key proteins on PI3K/AKT signaling pathway.Conclusions Selensh-enzhi prescription can control the occurrence and de-velopment of esophageal cancer through the synergistic effect of multi-components,multi-targets and multi-pathways,and provide a theoretical basis for further clinical investigation of the mechanism of selenshenzhi prescription in the treatment of esophageal cancer in the future.

Objective:To study the expression of the Homeobox C6(HOXC6)gene in the homeobox family in PCa,its effect on the biological behavior of PCa cells and its action mechanism.Methods:Based on the studies of HOXC6 retrieved from the data-base of Gene Expression Profiling Interactive Analysis(GEPIA),we analyzed the expression of HOXC6 in PCa and the relationship of its expression level with the survival prognosis of the patients.We detected the expression of the HOXC6 protein in PCa tissues and cells by Western blot,stably interfered with the expression of the HOXC6 gene in human PCa DU145 and PC-3 cells and normal prosta-tic epithelial RWPE-1 cells using the siRNA plasmid,and determined the effects of HOXC6 on the proliferation,migration and inva-siveness of PCa cells by CCK8,plate cloning and scratch healing and Transwell invasion assays.Using the GEPIA database,we ana-lyzed the correlation of the Wnt tumor inhibitory factor-secreted frizzled-related protein 1(SFRP1)gene with HOXC6,and detected the expressions of HOXC6,SFRP1,Wnt and β-catenin in PC-3 cells after siRNA-HOXC6 transfection by Western blot.Results:The expression of HOXC6 was dramatically higher in the PCa than in the normal prostate tissue(P<0.01),and in the PCa cells than in the normal prostatic epithelial cells(P<0.01).Bioinformatics analysis indicated a lower survival rate of the PCa patients with a high than those with a low HOXC6 expression(P=0.011).The relative expression of the HOXC6 protein,absorbance value,number of clones formed and number of invaded cells were significantly lower in the siRNA group than in the negative controls(P<0.05).Ac-cording to the GEPIA database,highly expressed SFRP1 was associated with a good prognosis of PCa,and the protein expressions of Wnt and β-catenin were markedly increased while that of SFRP1 decreased in the PCa PC-3 cell line(P<0.05).The expressions of the Wnt and β-catenin proteins were decreased and that of SFRP1 increased significantly in the siRNA-HOXC6 transfection group com-pared with those in the siRNA negative control and PCa PC-3 groups(P<0.05).Conclusion:HOXC6 is highly expressed in PCa tissues and related to the proliferation,migration and invasiveness of PCa cells.HOXC6 promotes the growth of DU145 and PC-3 cells in PCa by inhibiting the SFRP1/Wnt/β-catenin signaling pathway,and may be a potential target for clinical treatment of PCa.

Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specif-ically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

OBJECTIVE To systematically evaluate the effects of C3435T polymorphism in ABCB1 gene on lipid-lowering efficacy of statins. METHODS Retrieved from PubMed， Web of Science， the Cochrane Library， CNKI and VIP， the cohort studies on the use of statins were collected from the inception to November 1， 2023. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 11 literature involving 1 575 patients were included. The results showed that under the dominant genetic model， the reduction of low-density lipoprotein cholesterol （LDL-C） [MD＝－1.87， 95%CI （－3.62， －0.13）， P＝0.04]， total cholesterol （TC） [MD＝－1.42， 95%CI （－2.80， －0.04）， P＝0.04] in patients with CT+TT genotype was significantly higher than CC genotype. There was no significant difference in the increase of high-density lipoprotein cholesterol （HDL-C） [MD＝－0.65， 95%CI （－2.48， 1.18）， P＝0.49] or the decrease of triglyceride （TG） [MD＝－0.05， 95%CI （－2.94， 2.84）， P＝0.97] between patients with CT+TT genotype and CC genotype. Under the recessive genetic model， the reduction of TC [MD＝2.26， 95%CI （0.97， 3.56）， P＝0.000 6] and the increase of HDL-C [MD＝2.38， 95%CI （0.42， 4.35）， P＝0.02] in patients with TT genotype were significantly higher than CC+ CT genotype. There was no significant difference in the reduction of LDL-C [MD＝1.53， 95%CI （－0.10， 3.15）， P＝0.07] or TG [MD＝0.06， 95%CI （－2.98， 3.10）， P＝0.97] between CC+CT genotype and TT genotype. Under the additive genetic model， the reduction of TC [MD＝2.98， 95%CI （1.27， 4.69）， P＝0.000 6] and LDL-C [MD＝2.84， 95%CI （0.67， 5.01）， P＝0.01] in patients with TT genotype were significantly higher than CC genotype. There was no significant difference in the increase of HDL-C [MD＝2.40， 95%CI （－0.17， 4.97）， P＝0.07] or the decrease of TG [MD＝0.97， 95%CI 　　 （－2.93， 4.87）， P＝0.63] between patients with TT genotype and CC genotype. CONCLUSIONS The reduction of LDL-C and TC in patients with dyslipidemia treated with statins may be related to the heterozygous and homozygous mutation of C3435T in ABCB1 gene， and the reduction of LDL-C and TC in patients with CT or TT genotype is more obvious， compared with patients with CC genotype. The elevation of HDL-C may be related to homozygous mutation， and the effect of HDL-C elevation may be more obvious in patients with TT genotype， compared with CC+CT genotype. However， the change of TG may not be related to the C3435T polymorphism in ABCB1 gene.

Liver transplantation, as one of the radical treatment strategies for hepatocellular carcinoma, has a good clinical effect in patients meeting the Milan criteria; however, the high recurrence rate and metastasis rate after surgery bring great challenges to the long-term survival of such patients. Therefore, how to improve long-term survival rate and reduce postoperative tumor metastasis has become a key problem that needs to be solved urgently. In recent years, immune checkpoint inhibitors (ICIs), with their good safety and objective reactivity, have provided a new opportunity for the treatment of patients with advanced liver cancer and have become potential candidates for improving the therapeutic effect of liver transplantation. At present, early clinical studies have reported the unique advantages of ICIs used alone or in combination in downstaging or bridging therapy before liver transplantation for hepatocellular carcinoma and adjuvant therapy after liver transplantation. Therefore, this article reviews the clinical trials of ICIs in liver transplantation for hepatocellular carcinoma and the advances in the application of ICIs in recent years and discuss its safety and efficacy, in order to provide a certain reference for clinical medication.

OBJECTIVE To observe the changes in brain function characteristics of Chaihu Tongbian Decoction in rats with slow transit constipation(STC)and depression using resting-state functional magnetic resonance imaging(rs-fMRI).METHODS 70 healthy SPF grade male SD rats were randomly divided into the blank group,model group,mosapride group,fluoxetine hydrochloride group,low(11.02 g·kg-1),medium(22.05 g·kg-1),and high(44.1 g·kg-1)dose Chaihu Tongbian Decoction groups.A rat model of STC with depression was constructed using compound diphenylephrine tablets combined with solitary confinement and chronic unpredictable mild stress(CUMS).Drugs were administered after successful modeling.The general condition of the rats was observed;24 h total number of fecal particles,fecal water content and intestinal carbon end advance rate were calculated;HE staining of the co-lon tissue was performed;the depressive-like behavior of the rats was detected.By comparing rs-fMRI amplitude of low-frequency fluctuation(ALFF)values,the differences in neuronal activity in the brains of rats in each group were explored.RESULTS Com-pared with the blank group,the 24 h total number of fecal particles,fecal water content and intestinal carbon end advance rate in the model group were significantly reduced(P<0.01).HE staining showed that the colon tissue lesions in the model group were severe.Open field experiment and sugar water consumption showed that the activity level of rats in the model group decreased(P<0.01),and behavioral changes like anxiety and depression appeared.The rs-fMRI results showed that compared with the blank group,the ALFF value of the right posterolateral hippocampus in the model group decreased and the ALFF value of the left amygdala increased(P<0.01).Compared with the model group,after 4 weeks of treatment,the 24 h total number of fecal particles,fecal water content,and intestinal carbon end advance rate in the mosapride group and each dose group of Chaihu Tongbian Decoction were im-proved(P<0.05);compared with the model group,after 4 weeks of treatment,the fluoxetine hydrochloride group and each dose group of Chaihu Tongbian Decoction could improve the anxiety and depression-like behavior of rats(P<0.05);compared with the model group,after 4 weeks of treatment,the fluoxetine hydrochloride group and the high-dose Chaihu Tongbian Decoction group could in-crease the ALFF value of the right posterolateral hippocampus and decrease the ALFF value of the left amygdala(P<0.05).CON-CLUSION Chaihu Tongbian Decoction can effectively relieve constipation and depressive symptoms in STC rats with depression,and its mechanism may be related to activating the right posterolateral hippocampus and inhibiting amygdala activity.

As intelligent production of traditional Chinese medicine （TCM） has been inevitable， informatization and automation of the production process have become the precondition for realizing intelligent manufacturing of TCM， of which the accumulation of critical material attribute and the critical quality attribute are the basis. The study of material properties is of great significance to achieve the quality control of the final product in the process， but there is a lack of systematic induction and summary of the research on the attribute of TCM pills. Therefore， the authors analyzed and summarized the attributes of raw materials， excipients and intermediates in the pill unit process according to the classification of powder properties， rheological properties and texture properties. What’s more， the impact of material attributes on the quality of the final product was summarized. Besides， this review summarized the attribute characterization techniques involved in the pill process and provided some suggestions for the characterization of product quality attributes. Finally， based on the concept of quality by design （QbD）， the authors proposed that the study of material attribute should be combined with process analytical technology （PAT）， and the focus of drug quality control should be moved forward to guide equipment upgrading， so as to realize intelligent continuous manufacturing of TCM pills.

ObjectiveTo investigate the expression level of MMS21 and its functions in hepatocellular carcinoma. MethodsThe GEPIA2 and CPATC databases were used to analyze the mRNA and protein levels of MMS21 in adjacent and carcinoma tissues； the endogenous expression levels of MMS21 were reduced individually by two siRNAs. Meanwhile， flow cytometry was used to detect the distribution ratio of cell cycle of hepatocellular carcinoma cells. BrdU staining and DNA fiber assay were employed to determine cells proliferation rate， and colony assay was used to evaluate the ability of cell proliferation； the MYC tagged MMS21 was cloned and transfected into SK-hep1 to generate MMS21 stably overexpressed cells. Co-IP combined with mass spectrometry were used to identify MMS21-interacting proteome and map interactive pathway； Western Blot （WB） was performed to determine the effect of MMS21 towards cell cycle-related proteins. ResultsCompared with adjacent tissues （ n = 160 ）， MMS21 was significantly higher expressed in cancerous tissues （ n = 369；P < 0.05） and its high expression was associated with poor prognosis （ P < 0.01 ） in hepatocellular carcinoma； Knockdown of endogenous MMS21 by two siRNAs led to the increase of the proportion of cells in G0/G1 phase （P < 0.001； P < 0.01）， and the decrease of the ratio of cells in S （P < 0.01； P < 0.05）， G2/M （P < 0.05； P < 0.05） phase. Moreover， depletion of endogenous MMS21 greatly attenuated the speed of DNA replication （P < 0.000 1； P < 0.000 1） and the rate of cell proliferation （P < 0.01； P < 0.001）. Mass spectrometry analysis identified the total of 641 high-confidence proteins for MMS21， and interactive pathway analysis showed that these binding proteins were highly correlated with cell cycle-related genes. The results of Western Blot further confirmed this conclusion， and depletion of endogenous MMS21 markedly reduced the protein levels of Microchromosome maintenance protein family （MCMs）. ConclusionsMMS21 is highly expressed in hepatocellular carcinoma and positively correlated with the poor prognosis. MMS21 is closely related to the proliferation of Hepatocellular Carcinoma and regulated the stability of cell cycle related proteins and MCM family.

OBJECTIVE: To estimate the minimal clinically important difference (MCID) of the frequency of bowel movement for the patients with chronic severe functional constipation treated with acupuncture so as to provide the evidence for the clinical decision. METHODS: In this study, 813 patients with chronic severe functional constipation treated with acupuncture in two previous randomized controlled trials were included. Through the anchor-based method (anchored by the item 28 "satisfaction with previous treatment" of the patient assessment of constipation-quality of life [PAC-QOL]) and the distribution-based method, the MCID of the weekly frequency of complete spontaneous bowel movement (CSBM) and spontaneous bowel movement (SBM) was analyzed statistically in the patients. RESULTS: The MCID of the mean weekly frequency of CSBM and SBM was 1.3 times and 1.6 times in patients with chronic severe functional constipation treated with acupuncture, respectively. CONCLUSION The mean increase of the weekly CSMB is ≥ 1.3 times and that of SBM is ≥ 1.6 times after treatment when compared with the baseline respectively, suggesting the clinical significance.
Humans ; Quality of Life ; Minimal Clinically Important Difference ; Treatment Outcome ; Constipation/therapy* ; Acupuncture Therapy