This study was aimed at investigating differentially expressed genes(DEGs)in Clonorchis sinensis(C.sinensis)meta-cercariae and newly excysted juveniles(NEJs)cultured in vitro for 1 hour or 3 hours,through transcriptomic analysis.Our objective was to explore the mechanisms underlying host invasion.Metacercariae were digested and isolated from Pseudorasbora parva infected with C.sinensis.The metacercariae excysted and developed into NEJs in vitro.Subsequently,the mRNA of metacercariae and NEJs cultured in vitro for 1 hour or 3 hours was extracted for transcriptomic sequencing analysis to screen for DEGs,and to conduct GO and KEGG analyses.A protein-protein interaction network(PPI)was constructed to identify hub genes.A total of 1 218 DEGs were de-tected.The main enriched GO terms of DEGs included transcription regulator activity and gated channel activity(primarily K+).The KEGG pathways significantly enriched in DEGs included cholesterol metabolism,lysosome,synthesis,secretion,and action of para-thyroid hormone.ZFAND4-2,BIRC6,and other genes were screened and identified as hub genes through PPI network analysis.Addi-tionally,abundant differential expression of cathepsin-related genes,including Cathepsin L and Cathepsin F,were observed before and after excystment in C.sinensis.Therefore,significant transcriptional level changes occurred in the metacercariae of C.sinensis be-fore and after excystation,and enrichment was observed primarily in signaling pathways,such as activation of growth and material me-tabolism,that regulate parasite growth and development.Meanwhile,biological events conducive to parasite invasion,migration,and adhesion were triggered.

This study was aimed at investigating differentially expressed genes(DEGs)in Clonorchis sinensis(C.sinensis)meta-cercariae and newly excysted juveniles(NEJs)cultured in vitro for 1 hour or 3 hours,through transcriptomic analysis.Our objective was to explore the mechanisms underlying host invasion.Metacercariae were digested and isolated from Pseudorasbora parva infected with C.sinensis.The metacercariae excysted and developed into NEJs in vitro.Subsequently,the mRNA of metacercariae and NEJs cultured in vitro for 1 hour or 3 hours was extracted for transcriptomic sequencing analysis to screen for DEGs,and to conduct GO and KEGG analyses.A protein-protein interaction network(PPI)was constructed to identify hub genes.A total of 1 218 DEGs were de-tected.The main enriched GO terms of DEGs included transcription regulator activity and gated channel activity(primarily K+).The KEGG pathways significantly enriched in DEGs included cholesterol metabolism,lysosome,synthesis,secretion,and action of para-thyroid hormone.ZFAND4-2,BIRC6,and other genes were screened and identified as hub genes through PPI network analysis.Addi-tionally,abundant differential expression of cathepsin-related genes,including Cathepsin L and Cathepsin F,were observed before and after excystment in C.sinensis.Therefore,significant transcriptional level changes occurred in the metacercariae of C.sinensis be-fore and after excystation,and enrichment was observed primarily in signaling pathways,such as activation of growth and material me-tabolism,that regulate parasite growth and development.Meanwhile,biological events conducive to parasite invasion,migration,and adhesion were triggered.

Objective:To discuss the effect of cold exposure on nociception in the rats and its regulatory mechanism on transient receptor potential(TRP)ion channels in the sensory neurons,and to provide the basis for clarifying the biological mechanism of cold-sensitive pain.Methods:Sixteen female SD rats were divided into control group(n=8)and cold group(n=8).The rats in control group were exposed to the environment of(24±2)℃,and the rats in cold group were exposed to low temperature(4 ℃±1 ℃)in an artificial intelligence climate chamber for 4 h daily,for one week.Von Frey filaments were used to detect the mechanical withdrawal threshold(MWT)of the rats in two groups;immunofluorescence staining was used to observe the expression levels of TRPA1,TRPM8,TRPV1,and TRPV4 in dorsal root ganglion(DRG)tissue of the rats in two groups,the expression levels of calcitonin gene-related peptide(CGRP)and substance P(SP)in DRG tissue of the rats in two groups,and the expression levels of TRPA1,TRPM8,TRPV1,and TRPV4 in synovial tissue of the rats in two groups.Results:Compared with control group,the MWT of the rats in cold group was significantly decreased(P＜0.05),the expression levels of TRPA1 and TRPM8 in DRG tissue were significantly increased(P＜0.05),the expression level of TRPV1 was significantly decreased(P＜0.05),there was no significant difference in the expression level of TRPV4(P＞0.05),and the expression levels of CGRP and SP were significantly increased(P＜0.05).Compared with control group,the expression level of TRPA1 in synovial tissue of the rats in cold group was significantly increased(P＜0.05),while the expression levels of TRPM8,TRPV1,and TRPV4 were significantly decreased(P＜0.05).Conclusion:Short-term cold exposure can induce the hyperalgesia of the rats,and its mechanism may be associated with the changes in the expression of TRP ion channels in DRG and synovial tissues.TRPA1 sensory neurons play an important role in local joint cold pain.

OBJECTIVE To explore the short-term and long-term efficacy of bevacizumab combined with paclitaxel （PTX） and carboplatin （CBP） chemotherapy in the treatment of persistent or recurrent cervical cancer， as well as its impact on patient quality of life， tumor markers and safety. METHODS Totally 80 patients with persistent or recurrent cervical cancer admitted to our hospital from January 2020 to October 2022 were randomly divided into control group （40 cases） and observation group （40 cases） using a random number table method. Both groups received PTX+CBP chemotherapy， while the observation group was treated with bevacizumab in combination. Both groups were treated continuously for 6 cycles. The recent efficacy， the incidence of toxic side effects as well as European Organization for Research and Treatment of Cancer Life Questionnaire Core 30 （EORTC QLQ-C30） scores， and the serum tumor markers [carcinoembryonic antigen （CEA）， carbohydrate antigen 125 （CA125）， and squamous cell carcinoma antigen （SCCA）] levels before and at the end of the entire course of treatment were compared between two groups. The survival curves of the two groups were drawn by using Kaplan-Meier method， and progression-free survival （PFS） and overall survival （OS） were compared between the two groups by Log-rank test. RESULTS The objective response rate of the observation group was significantly higher than that of the control group （62.50% vs. 35.00%， P＜0.05）， and the median PFS （9.30 months vs. 6.30 months） and median OS （14.90 months vs. 10.60 months） were also significantly longer than the control group （P＜0.05）. EORTC QLQ-C30 score of the observation group after treatment was significantly higher than that of the control group （P＜0.05）. Compared to before treatment， the serum levels of CEA， CA125 and SCCA in both groups were significantly reduced after treatment （P＜0.05）， while the observation group had a larger decrease （P＜0.05）. There was no significant difference in the grading of various types of toxic side effects between the two groups during treatment （P＞0.05）. Most patients experienced automatic disappearance of toxic side effects 1-2 months after discontinuation of medication， or symptoms disappearance after symptomatic treatment. CONCLUSIONS The combination of bevacizumab and PTX+CBP chemotherapy regimen can effectively improve the objective efficacy rate of persistent or recurrent cervical cancer， reduce serum tumor marker levels， improve patient quality of life， prolong survival， and have good safety.