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.

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.

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.

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.

Objective: To develop a model incorporating radiomic features and clinical factors to accurately predict acute ischemic stroke (AIS) outcomes. Materials and Methods: Data from 522 AIS patients (382 male [73.2%]; mean age ± standard deviation, 58.9 ± 11.5 years) were randomly divided into the training (n = 311) and validation cohorts (n = 211). According to the modified Rankin Scale (mRS) at 6 months after hospital discharge, prognosis was dichotomized into good (mRS ≤ 2) and poor (mRS > 2); 1310 radiomics features were extracted from diffusion-weighted imaging and apparent diffusion coefficient maps. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator logistic regression method were implemented to select the features and establish a radiomics model. Univariable and multivariable logistic regression analyses were performed to identify the clinical factors and construct a clinical model. Ultimately, a multivariable logistic regression analysis incorporating independent clinical factors and radiomics score was implemented to establish the final combined prediction model using a backward step-down selection procedure, and a clinical-radiomics nomogram was developed. The models were evaluated using calibration, receiver operating characteristic (ROC), and decision curve analyses. Results: Age, sex, stroke history, diabetes, baseline mRS, baseline National Institutes of Health Stroke Scale score, and radiomics score were independent predictors of AIS outcomes. The area under the ROC curve of the clinical-radiomics model was 0.868 (95% confidence interval, 0.825–0.910) in the training cohort and 0.890 (0.844–0.936) in the validation cohort, which was significantly larger than that of the clinical or radiomics models. The clinical radiomics nomogram was well calibrated (p > 0.05). The decision curve analysis indicated its clinical usefulness. Conclusion The clinical-radiomics model outperformed individual clinical or radiomics models and achieved satisfactory performance in predicting AIS outcomes.

Objective: To explore the performance of a self-made venous-venous bypass (VVB) device for liver transplantation based on the principle of magnetic levitation drive. Methods: Experimental study was conducted from August 2020 to January 2022. Eight Bama minipigs underwent VVB of hepatic portal vein-femoral vein-internal jugular vein after occlusion of hepatic portal vein and inferior vena cava. The animals were divided into two groups according to the VVB devices used during VVB. A self-made VVB device was used in group A(n=5),and an imported VVB device was used in group B(n=3). The hemodynamic changes of the two groups of animals were compared at 6 time points including before vascular occlusion, during vascular occlusion, 30 minutes, 60 minutes, 90 minutes after the start of VVB, and 30 minutes after vascular opening. In addition,the changes of blood compatibility indexes,intestinal injury indexes,kidney injury indexes and internal environment indexes of the two groups of animals at each time point were compared. The independent samples t test was used for the quantitative data between the two groups with non-repeated measures,and the repeated measures analysis of variance was used for the quantitative data between the two groups with repeated measures. Results: During the VVB of the two devices,the venous drainage was sufficient,and the main manifestations were that the color of the intestine of the Bama miniature pig was ruddy, the peristalsis was normal, and the urine output was normal. There were no significant differences in hemodynamics,blood injure indexes,intestinal injury indexes,kidney injury indexes,neutropil gelatinase-associated lipocalin,and internal environment indexes(all P>0.05).The indexes at 30 minutes after vascular opening in the group A and the group B were as follows:mean arterial pressure were (71.0±7.7)mmHg(1 mmHg=0.133 kPa) and (74.0±8.7)mmHg,central venous pressure were (7.0±1.4)cmH₂O(1 cmH₂O=0.098 kPa) and (7.7±0.6)cmH₂O,heart rate were (131±10) beats/minutes and (132±8)beats/minutes; red blood cell count were (6.43±0.89)×10¹²/L and (6.32±0.58)×10¹²/L,hemoglobin were (108.4±5.9)g/L and (110.0±3.5)g/L,free hemoglobin were (78.28±3.96)mg/L and (78.08±4.54)mg/L; intestinal fatty acid binding protein were (2.27±0.49)μg/L and (2.40±0.78)μg/L;creatinine were (68.30±9.77)μmol/L and (79.90±26.91)μmol/L,blood urea nitrogen were (3.94±1.39)mmol/L and (3.45±0.65)mmol/L;neutropil gelatinase-associated lipocalin were (4.02±0.53) μg/L and (3.86±0.23)μg/L;pH value were 7.27±0.04 and 7.23±0.03,lactic acid were (6.18±2.62)mmol/L and (4.30±0.50)mmol/L,concentrations of Na⁺ were (136.3±3.0)mmol/L and (137.6±1.6) mmol/L,concentrations of K⁺ were (3.89±0.42) mmol/L and (3.98±0.17)mmol/L,concentrations of Ca²⁺ were (1.40±0.03)mmol/L and(1.40±0.04)mmol/L;all indexes in the two group had no differences(all P>0.05). Conclusion: The self-made venous bypass device can be safely and effectively applied to VVB of Bama minipigs,and achieves the same performance as the imported venous bypass device.
Animals ; Creatinine ; Fatty Acid-Binding Proteins ; Gelatinases ; Lactic Acid ; Lipocalins ; Liver Transplantation ; Magnetic Phenomena ; Portal Vein/surgery* ; Swine ; Swine, Miniature

ObjectiveTo explore the regulatory effect of Gouqi chewable tablets on innate and adaptive immunity in normal mice and its antioxidant activity in vitro and in vivo. MethodThe effects of low-， medium-， and high-dose groups （0.25， 0.5， 1.5 g·kg^-1） on the immune function of normal mice were observed by carbon clearance test， immune organ index test， serum hemolysin test， ConA-induced splenic lymphocyte proliferation test， and natural killer cell （NK cell） activity test. The effects of Gouqi chewable tablets on the antioxidant capacity in vivo were determined by detecting the content of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） in mice serum. The in vitro antioxidant activity of Gouqi chewable tablets was detected by 2，2'-azino-bis（3-ethylbenzothiazoline-6-sulfonic acid） diammonium salt （ABTS）， 2，2-diphenyl-1-picrylhydrazyl （DPPH）， and hydroxyl radical scavenging tests. ResultCompared with the blank control group， the low-， medium-， and high-dose groups of Gouqi chewable tablets improved the viability of NK cells， the proliferation of splenic lymphocytes， and the level of serum hemolysin antibody in mice （P<0.05）. The high-dose group increased the thymus index， spleen index， and phagocytic function of macrophages （P<0.05， P<0.01）. As compared with the blank control group， the activity of GSH-Px in mice serum in the medium-dose group was increased （P<0.05）， and the content of MDA in mice serum in the high-dose group was decreased （P<0.05）. In in vitro antioxidant tests， the median inhibitory concentration （IC₅₀） values of Gouqi chewable tablets were 1.64±0.20， 2.04±0.03， and 10.27±0.03 g·L^-1 by the DPPH， ABTS， and OH^- free radical method， respectively. Those results indicated that Gouqi chewable tablets have good antioxidant effects in vitro. ConclusionGouqi chewable tablets can enhance the immune function of mice with good antioxidant effects.