[摘 要] 目的：探讨胰岛素样生长因子2 mRNA结合蛋白3（IGF2BP3）、尿苷二磷酸-葡萄糖醛酸脱羧酶1（UXS1）在肝细胞癌（HCC）中的表达特征、预后价值及两者协同作用的分子机制。方法：整合UALCAN、cBioPortal、ENCORI、TISCH2、GDSC等公共数据库的转录组数据，对IGF2BP3和UXS1进行表达、预后评估、功能富集及药物敏感性等分析。收集GEO数据库的单细胞RNA测序（scRNA-seq）数据，分析细胞通信、单细胞代谢评分，系统解析IGF2BP3-UXS1轴在HCC中的具体作用。结果：IGF2BP3、UXS1在HCC组织中均显著高表达，且高表达患者总生存期显著缩短（均P < 0.05）。采用CRISPP技术敲除IGF2BP3或UXS1后，多种HCC细胞的增殖能力受到明显抑制。scRNA-seq分析揭示了IGF2BP3、UXS1在肝细胞等细胞类型中的广泛表达分布，前者在细胞分化晚期上调，后者则在细胞分化早、中期高表达。IGF2BP3、UXS1高表达组均显著激活了MIF通路，同时IGF2BP3的高表达削弱了成纤维细胞的相互作用，而UXS1的高表达则增强了T细胞的信号转导功能。IGF2BP3与UXS1在表达相关性中存在显著的正相关（r = 0.432，P < 0.05）。沉默IGF2BP3结合位点会导致UXS1表达水平变化（F = 0.333）。功能富集分析提示，IGF2BP3与UXS1协同调控能量代谢、蛋白质翻译等生物学过程。在IGF2BP3或UXS1高表达的细胞亚群中，发现两者与多个糖代谢相关通路存在显著关联。IGF2BP3、UXS1高表达的患者对优普色替等药物表现出显著的敏感性，还对药物那维托克等表现出显著的耐药性。结论： IGF2BP3、UXS1在HCC中高表达，两者通过调控糖代谢重编程的协同作用促进HCC恶性生物学行为。

This study was aimed at exploring the mechanism underlying the effects of nitidine chloride against Talaromyces marnef-fei through network pharmacology analysis.We collected NC and TM action targets from various databases;constructed a protein-protein interaction(PPI)network by using common drug and disease targets;and performed KEGG pathway and GO enrichment analy-ses.In vitro cellular experiments were conducted to test the antibacterial ability of NC at various concentrations,qPCR was used to de-tect the mRNA expression of genes in the target pathway,and WB was used to examine the expression of proteins associated with tar-get signaling pathways in cells.We identified 153 target genes for NC and 2 095 target genes for TM,among which 23 targets over-lapped.By integrating the PPI network with KEGG enrichment analysis,we selected key target genes in the MAPK signaling pathway,such as FLT1,FLT3,CD38,and PRF1.The CFU results indicated that NC had favorable antibacterial capability.Moreover,qPCR demonstrated that NC downregulated the mRNA expression of FLT1,FLT3,and RPS6KA3,and upregulated the mRNA expression of MAP3K8.WB findings indicated that NC downregulated the expression of RSK2,VEGF,and FLT3 proteins,and upregulated the ex-pression of MAP3K8 protein.NC may exert its anti-TM effects by downregulating the expression of RSK2,VEGF,and FLT3 proteins,thereby inhibiting MAPK pathway activation.The potential targets and signaling pathways underlying NC's anti-TM action may pro-vide new insights to guide the clinical application of NC.

Background and purpose:High-throughput detection of plasma cell-free DNA(cfDNA)is widely used for multi-cancer targeted therapy drug screening,and this study investigated the relationship between the type and number of plasma cfDNA class Ⅰ and Ⅱ targeted therapy-related gene variants and cancer survival in patients with non-small cell lung cancer(NSCLC).Methods:The sequencing results and clinical data of NSCLC patients who underwent tumor plasma cfDNA high-throughput sequencing projects in Sun Yat-sen University Cancer Center from 2021 to 2023 were collected.The survival follow-up of enrolled patients was carried out from the day of plasma collection on June 1,2021 to May 27,2024,and GraphPad Prism 8.0 and SPSS Statistics 25.0 were used.Univariate and multivariate statistical analyses were conducted on the types and numbers of class Ⅰ and class Ⅱ targeted therapy-related genes in the survival and clinical data of patients and sequencing results(Ethical approval:B2024-359-01).Results:A total of 313 patients included in this study with NSCLC were categorized into stage Ⅰ 25 patients(7.98%),stageⅡ 20 patients(6.39%),stage Ⅲ 38patients(12.14%),and stage Ⅳ 230 patients(73.48%).Pathological diagnosis results showed that adenocarcinoma accounted for 90.10%,squamous cell carcinoma accounted for 5.11%,large cell carcinoma accounted for 2.87%and other classifications accounted for 1.92%.The number and the percentage of class Ⅰ and class Ⅱ targeted therapy drug-related genes in the plasma cfDNA NSCLC patients were 0(25.24%),1(17.57%),2(19.17%),3(14.38%),4(8.31%),and 5 or more(15.34%).The results of statistical analysis showed that 3 genes with the highest mutation frequencies were EGFR,TP53 and ERBB2,and the mutation frequency of EGFR gene was 36.04%.The mutation frequency of TP53 gene was 30.63%.The mutation frequency of ERBB2 gene was 4.95%.The survival time of patients is related to not only the expression of hotspot targeted genes,but also the number of class Ⅰ and Ⅱ target-related gene variants detected by plasma cfDNA high-throughput sequencing.The survival time of the patients with no targeted therapy-related locus variants after treatment was longer compares with targeted therapy-related locus variants,which can reduce the risk of death by 63.2%.However,patients with a single gene locus variant had longer survival time and lower risk of death than those with multiple driver locus variants,and the measured class Ⅰ and Ⅱ targeted therapy drugs were within 3 genes.Overall,the smaller the number of genes,the longer the survival.Conclusions:The number of class Ⅰ and class Ⅱtargeted therapy-related gene variants in plasma cfDNA high-throughput sequencing also has an effect on the survival of patients after treatment.Plasma cfDNA level detected by high-throughput sequencing could be a prognostic factor for the NSCLC patients.

Objective:To study effects and mechanism of platelet-rich plasma combined with periodic mechanical stretch on C2C12 myotube atrophy.Method:The expression of MyoD and MyoG was detected by Westem Blot(WB)to confirm the optimal con-centration of PRP;Subsequently,the pro-differentiation effect of PRP and periodic mechanical stretch(Str)on C2C12 cells was explored;C2C12 cells were induced to shrink by TNF-α,and the models were verified by Modified Giemsa staining.To explore the effect and mechanism of 2％PRP combined with periodic mechanical stretching in improving the atrophy of C2C12 cells,the experiments were divided into control group,TNF-αgroup,TNF-α+2％PRP group,TNF-α+2％PRP+Str group.The changes of MuRF-1,Fbx32 and Akt,p-Akt,p70 and p-p70 were detected by adding the inhibitors.Result:The expression levels of MyoD and MyoG in the 2％PRP group and the 2％PRP+Str group were significantly increased.In the anti-atrophy experiment,the modified Giemsa staining showed the myotubes in the TNF-α group were significantly atrophied,and the TNF-α+2％PRP group can improve myotube atrophy.The expressions of MuRF-l and Fbx32 were decreased in the TNF-α+2％PRP+Str group.After GDC0068 inter-vention,the anti-atrophic effect of PRP combined with periodic mechanical stretch was inhibited.Conclusion:2％PRP combined with periodic mechanical stretch can effectively promote the differentiation of C2C12 cells,improve myotube atrophy,and play a role through the Akt/p70 signaling pathway.

Background and purpose:High-throughput detection of plasma cell-free DNA(cfDNA)is widely used for multi-cancer targeted therapy drug screening,and this study investigated the relationship between the type and number of plasma cfDNA class Ⅰ and Ⅱ targeted therapy-related gene variants and cancer survival in patients with non-small cell lung cancer(NSCLC).Methods:The sequencing results and clinical data of NSCLC patients who underwent tumor plasma cfDNA high-throughput sequencing projects in Sun Yat-sen University Cancer Center from 2021 to 2023 were collected.The survival follow-up of enrolled patients was carried out from the day of plasma collection on June 1,2021 to May 27,2024,and GraphPad Prism 8.0 and SPSS Statistics 25.0 were used.Univariate and multivariate statistical analyses were conducted on the types and numbers of class Ⅰ and class Ⅱ targeted therapy-related genes in the survival and clinical data of patients and sequencing results(Ethical approval:B2024-359-01).Results:A total of 313 patients included in this study with NSCLC were categorized into stage Ⅰ 25 patients(7.98%),stageⅡ 20 patients(6.39%),stage Ⅲ 38patients(12.14%),and stage Ⅳ 230 patients(73.48%).Pathological diagnosis results showed that adenocarcinoma accounted for 90.10%,squamous cell carcinoma accounted for 5.11%,large cell carcinoma accounted for 2.87%and other classifications accounted for 1.92%.The number and the percentage of class Ⅰ and class Ⅱ targeted therapy drug-related genes in the plasma cfDNA NSCLC patients were 0(25.24%),1(17.57%),2(19.17%),3(14.38%),4(8.31%),and 5 or more(15.34%).The results of statistical analysis showed that 3 genes with the highest mutation frequencies were EGFR,TP53 and ERBB2,and the mutation frequency of EGFR gene was 36.04%.The mutation frequency of TP53 gene was 30.63%.The mutation frequency of ERBB2 gene was 4.95%.The survival time of patients is related to not only the expression of hotspot targeted genes,but also the number of class Ⅰ and Ⅱ target-related gene variants detected by plasma cfDNA high-throughput sequencing.The survival time of the patients with no targeted therapy-related locus variants after treatment was longer compares with targeted therapy-related locus variants,which can reduce the risk of death by 63.2%.However,patients with a single gene locus variant had longer survival time and lower risk of death than those with multiple driver locus variants,and the measured class Ⅰ and Ⅱ targeted therapy drugs were within 3 genes.Overall,the smaller the number of genes,the longer the survival.Conclusions:The number of class Ⅰ and class Ⅱtargeted therapy-related gene variants in plasma cfDNA high-throughput sequencing also has an effect on the survival of patients after treatment.Plasma cfDNA level detected by high-throughput sequencing could be a prognostic factor for the NSCLC patients.

Objective:To study effects and mechanism of platelet-rich plasma combined with periodic mechanical stretch on C2C12 myotube atrophy.Method:The expression of MyoD and MyoG was detected by Westem Blot(WB)to confirm the optimal con-centration of PRP;Subsequently,the pro-differentiation effect of PRP and periodic mechanical stretch(Str)on C2C12 cells was explored;C2C12 cells were induced to shrink by TNF-α,and the models were verified by Modified Giemsa staining.To explore the effect and mechanism of 2％PRP combined with periodic mechanical stretching in improving the atrophy of C2C12 cells,the experiments were divided into control group,TNF-αgroup,TNF-α+2％PRP group,TNF-α+2％PRP+Str group.The changes of MuRF-1,Fbx32 and Akt,p-Akt,p70 and p-p70 were detected by adding the inhibitors.Result:The expression levels of MyoD and MyoG in the 2％PRP group and the 2％PRP+Str group were significantly increased.In the anti-atrophy experiment,the modified Giemsa staining showed the myotubes in the TNF-α group were significantly atrophied,and the TNF-α+2％PRP group can improve myotube atrophy.The expressions of MuRF-l and Fbx32 were decreased in the TNF-α+2％PRP+Str group.After GDC0068 inter-vention,the anti-atrophic effect of PRP combined with periodic mechanical stretch was inhibited.Conclusion:2％PRP combined with periodic mechanical stretch can effectively promote the differentiation of C2C12 cells,improve myotube atrophy,and play a role through the Akt/p70 signaling pathway.

This study was aimed at exploring the mechanism underlying the effects of nitidine chloride against Talaromyces marnef-fei through network pharmacology analysis.We collected NC and TM action targets from various databases;constructed a protein-protein interaction(PPI)network by using common drug and disease targets;and performed KEGG pathway and GO enrichment analy-ses.In vitro cellular experiments were conducted to test the antibacterial ability of NC at various concentrations,qPCR was used to de-tect the mRNA expression of genes in the target pathway,and WB was used to examine the expression of proteins associated with tar-get signaling pathways in cells.We identified 153 target genes for NC and 2 095 target genes for TM,among which 23 targets over-lapped.By integrating the PPI network with KEGG enrichment analysis,we selected key target genes in the MAPK signaling pathway,such as FLT1,FLT3,CD38,and PRF1.The CFU results indicated that NC had favorable antibacterial capability.Moreover,qPCR demonstrated that NC downregulated the mRNA expression of FLT1,FLT3,and RPS6KA3,and upregulated the mRNA expression of MAP3K8.WB findings indicated that NC downregulated the expression of RSK2,VEGF,and FLT3 proteins,and upregulated the ex-pression of MAP3K8 protein.NC may exert its anti-TM effects by downregulating the expression of RSK2,VEGF,and FLT3 proteins,thereby inhibiting MAPK pathway activation.The potential targets and signaling pathways underlying NC's anti-TM action may pro-vide new insights to guide the clinical application of NC.

Objective To investigate the risk factors of complications after CT-guided percutaneous transthoracic needle biopsy(PTNB)in the plateau environment.Methods A total of 858 patients who underwent CT-guided PTNB were selected,and the clini-cal data of patients,imaging features of lesions,information related to puncture operation,complications,and pathological results were analyzed retrospectively,then the independent risk factors of postoperative pneumothorax and pulmonary hemorrhage were summarized.Results Among 858 patients with lung biopsy,816 cases(95.1％)were successfully sampled,including 203 cases(23.7％)in the pneumothorax and 140 cases(16.3％)in the pulmonary hemorrhage.The statistical analysis results of the pneumo-thorax revealed significant differences in lesion location and lesion size(P＜0.05).The statistical analysis results of the pulmonary hemorrhage showed significant differences in lesion location,lesion size,puncture angle and puncture depth(P＜0.05).Independent risk factors affecting pneumothorax and pulmonary hemorrhage were illustrated in a forest plot.Conclusion Because the oxygen partial pressure and climate temperature are relatively low in the plateau environment,the cardiopulmonary function of patients will be affected by the living environment.Therefore,on the premise of ensuring the success rate of CT-guided PTNB,the optimal path and timing should be selected to reduce the risk of complications.

Objective To investigate the efficacy of CT-guided percutaneous microwave ablation for the treatment of primary hepatocellular carcinoma.Methods A total of 132 patients with primary hepatocellular carcinoma were divided into control group and study group(66 cases in each group)according to different treatment plans.The control group received transcatheter arterial chemoembolization(TACE)treatment,while the study group received TACE combined with percutaneous microwave ablation under CT guidance.The changes in serum tumor markers and liver function indicators were observed before and after treatment in the two groups,and the efficacy(short-and long-term)and safety of the two groups were compared.Results The levels of serum carcinoembryonic antigen(CEA),alpha-fetoprotein(AFP),carbohydrate antigen 125(CA125),and carbohydrate antigen 19-9(CA19-9)in both groups decreased significantly after treatment compared to those before treatment,and intergroup comparison showed that the levels of CEA,AFP,CA125,and CA1 9-9 in the study group were significantly lower those after treatment(P＜0.05).Compared with those before treatment,the levels of alanine transaminase(ALT)and aspartate transaminase(AST)were decreased,and the level of albumin(ALB)was increased of both groups after treatment.The intergroup comparison showed that the study groups ALT and AST levels were lower and ALB level was higher(P＜0.05).The total effective rate of the study group was clearly higher than that of the control group(75.76％vs 46.97％,P＜0.05).The 1-year survival rates of the two groups were similar(90.91％vs 81.82％,P＞0.05),however,the 2-year survival rate of the study group was clearly higher than that of the control group(84.85％vs 63.64％,P＜0.05).Conclusion CT-guided percutaneous microwave ablation for the adjuvant TACE treatment of primary hepatocellular carcinoma can effectively reduce tumor burden and lower tumor marker levels,its short-and long-term efficacy is significant,with a low incidence of adverse reactions and good safety.

Glioma is the most common primary tumor of the brain,accounting for 81%of central nervous system(CNS)malignant tumors.The degree of malignancy is high,and the current treatment methods are limited.In recent years,with the in-depth study of intestinal flora and brain-gut axis,it has been found that the diversity of gut microbiota plays an important role in the regulation of glioma.The mechanism is that the intestinal flora affects the development of glioma through the role of immune regulation and metabolites.In addition,it has been con-firmed that there is a certain correlation between some probiotics and glioma,which provides a new application prospect for the treatment of glioma.This paper discusses the main intestinal bacteria that regulate gliomas as well as the role and regulatory mechanisms of intestinal flora in the development of gliomas,and provides ideas for the discovery of new targets for glioma treatment and further improvement of treatment options.