Objective:To screen differentially expressed genes (DEGs) associated with liver cancer by bioinformatics analysis method, and to investigate the mechanism of the minichromosome maintenance protein 2 ( MCM2) and replication factor C subunit 4 ( RFC4) genes in liver cancer in vitro. Methods:Gene expression profiling data of 80 and 36 hepatocellular carcinoma tissues and 307 and 13 cirrhotic tissues were obtained from the GSE25097 and GSE98620 datasets of the gene expression analysis (GEO) database, respectively. Gene expression profiling data of 374 liver cancer tissues and 50 normal liver tissues were downloaded from the cancer genome atlas (TCGA) database. Limma and DESeqs R software were used to process the gene expression profiling data, construct protein-protein interaction networks, and analysis the relevance of these genes to survival. Weighted gene co-expression network analysis was performed to screen out the core genes. Liver cancer SMMC7721 cells were transfected with MCM2 blank plasmid (MCM2 control group), MCM2 overexpression plasmid [MCM2 WT1 group, MCM2 WT2 (2-fold WT1) group], RFC4 blank plasmid (RFC4 control group), and RFC4 overexpression plasmid [RFC4 WT1 group, RFC4 WT2 (2-fold WT1) group], respectively. The expression of MCM2 and RFC4 in liver cancer cell lines and their transfection levels were detected by real-time fluorescence quantitative reverse transcription PCR and Western blotting. The effects of MCM2 and RFC4 on the proliferation of hepatocellular carcinoma cells were detected by MTT assay and cell cloning assay, respectively. The effects of MCM2 and RFC4 on the migration of liver cancer cells were determined by the scratch assay. The effects of MCM2 and RFC4 on liver cancer cell invasion were detected by Transwell assay.Results:By bioinformatic analysis, 9 HCC DEGs were selected, including ubiquitin conjugating enzyme E2 T ( UBE2T), aurora kinase A ( AURKA), targeting protein for Xklp2 ( TPX2), MCM2, RFC4, ribonucleoside-diphosphate reductase subunit M2 ( RRM2), serine peptidase inhibitory factor Kazal type 1 ( SPINK1), collagen type XV alpha 1 chain ( COL15A1) and C-C motif chemokine 25 ( CCL25). Among the six genes associated with clinical stages, the MCM2 and RFC4 genes were found to be strongly associated with prognosis in liver cancer. The relative protein expression of MCM2 and RFC4 in HepG2 cells (1.83±0.07, 1.44±0.09) and SMMC7721 cells (1.74±0.05, 1.43±0.08) was higher than that in MIHA cells (1.00±0.02, 1.00±0.03), and all the differences were statistically significant (all P<0.05). The relative gene expression of MCM2 and RFC4 in HepG2 cells (14.30±0.12, 5.10±0.18) and SMMC7721 cells (10.60±0.11, 7.60±0.07) was higher than that in MIHA cells (1.00±0.05, 1.00±0.03), and all the differences were statistically significant (all P<0.05). Compared with the MCM2 control group, the absorbance values [(0.28±0.01 and 0.21±0.01) vs 0.18±0.03], the number of clonal cells [(717±12 and 782±29) cells vs (389±17) cells], the percentage migration [(0.43±0.02 and 0.68±0.01) vs 0.15±0.06], and the number of cellular invasions [(933±21 and 821±11) cells vs (409±16) cells] were higher in the MCM2 WT1 and MCM2 WT2 groups, and the differences were all statistically significant (all P<0.05). Compared with the RFC4 control group, the absorbance values [(0.30±0.02 and 0.21±0.01) vs 0.17±0.02], the number of cloned cells [(571±11 and 728±9) cells vs (373±23) cells], the percentage migration [(0.75±0.11 and 0.67±0.04) vs 0.34±0.07], and the number of cell invasion [(835±26 and 818±18) cells vs (629±12) cells] were higher in the RFC4 WT1 and the RFC4 WT2 groups, and the differences were statistically significant (all P<0.05). Conclusions:MCM2 and R FC4 genes play a role in promoting tumorigenesis and growth in hepatocellular carcinoma.

Objective:To compare the efficacy and safety of Dienogest(DNG)with other drugs in non-surgi-cal pharmacologic treatment and long-term management of drugs after conservative surgery for endometriosis(EMT).Methods:We searched PubMed,Embase,Medline,Google Scholar,Cochrane Library,China National Knowledge Infrastructure,Wanfang,and Weipu databases from the establishment of the database until December 31,2023 for relevant literature on EMT pharmacotherapy.Meta-analysis was performed using Stata 18.0 software to assess the efficacy of DNG,gonadotropin-releasing hormone agonist(GnRH-a),compound short-acting oral contraceptive(COC)and levonorgestrel intrauterine sustained-release system(LNG-IUS)in reducing the diameter of ovarian endometrioma(OMA),relieving pelvic pain and preventing EMT postoperative recurrence in EMT pa-tients after non-surgical drug treatment and conservative surgery,as well as the adverse reactions of drugs.Re-sults:①During non-surgical medication treatment of EMT,there was no statistically significant difference(P＞0.05)between DNG and GnRH-a in reducing OMA diameter and relieving pelvic pain.Compared with COC,DNG was superior to COC in reducing the diameter of OMA(WMD 10.44 mm,P=0.017)and relieving pelvic pain(WMD 12.20 mm,P＜0.001).②During long-term medication management after conservative EMT surger-y:there was no statistically significant difference(P＞0.05)between DNG,GnRH-a,COC and LNG-IUS in re-ducing postoperative recurrence and controlling pelvic pain significant(P＞0.05).③Adverse drug reactions:com-pared with GnRH-a,DNG had a reduced risk of bone loss(bone density WMD2.78 g/cm3,P=0.038),hot fla-shes(OR 0.07,P＜0.001),and an increased risk of irregular vaginal bleeding(OR 19.10,P＜0.001);com-pared with COC,the risk of weight gain,mood abnormalities,and breast tenderness,nausea and vomiting,and sleep disorders in DNG were reduced(OR＜1,P＜0.05);compared with LNG-IUS,the risk of abnormalities of mood in DNG was increased(OR 9.87,P=0.033).Conclusions:DNG treatment is more effective than COC in non-surgical drug therapy for EMT.When supplemental medication was given after conservative EMT surgery,DNG,like other drugs,can effectively prevent postoperative recurrence and control pelvic pain.The safety of DNG is superior to GnRH-a and COC,slightly inferior to LNG-IUS.

Objective:To compare the efficacy and safety of Dienogest(DNG)with other drugs in non-surgi-cal pharmacologic treatment and long-term management of drugs after conservative surgery for endometriosis(EMT).Methods:We searched PubMed,Embase,Medline,Google Scholar,Cochrane Library,China National Knowledge Infrastructure,Wanfang,and Weipu databases from the establishment of the database until December 31,2023 for relevant literature on EMT pharmacotherapy.Meta-analysis was performed using Stata 18.0 software to assess the efficacy of DNG,gonadotropin-releasing hormone agonist(GnRH-a),compound short-acting oral contraceptive(COC)and levonorgestrel intrauterine sustained-release system(LNG-IUS)in reducing the diameter of ovarian endometrioma(OMA),relieving pelvic pain and preventing EMT postoperative recurrence in EMT pa-tients after non-surgical drug treatment and conservative surgery,as well as the adverse reactions of drugs.Re-sults:①During non-surgical medication treatment of EMT,there was no statistically significant difference(P＞0.05)between DNG and GnRH-a in reducing OMA diameter and relieving pelvic pain.Compared with COC,DNG was superior to COC in reducing the diameter of OMA(WMD 10.44 mm,P=0.017)and relieving pelvic pain(WMD 12.20 mm,P＜0.001).②During long-term medication management after conservative EMT surger-y:there was no statistically significant difference(P＞0.05)between DNG,GnRH-a,COC and LNG-IUS in re-ducing postoperative recurrence and controlling pelvic pain significant(P＞0.05).③Adverse drug reactions:com-pared with GnRH-a,DNG had a reduced risk of bone loss(bone density WMD2.78 g/cm3,P=0.038),hot fla-shes(OR 0.07,P＜0.001),and an increased risk of irregular vaginal bleeding(OR 19.10,P＜0.001);com-pared with COC,the risk of weight gain,mood abnormalities,and breast tenderness,nausea and vomiting,and sleep disorders in DNG were reduced(OR＜1,P＜0.05);compared with LNG-IUS,the risk of abnormalities of mood in DNG was increased(OR 9.87,P=0.033).Conclusions:DNG treatment is more effective than COC in non-surgical drug therapy for EMT.When supplemental medication was given after conservative EMT surgery,DNG,like other drugs,can effectively prevent postoperative recurrence and control pelvic pain.The safety of DNG is superior to GnRH-a and COC,slightly inferior to LNG-IUS.

Objective:To compare the efficacy and safety of Dienogest(DNG)with other drugs in non-surgi-cal pharmacologic treatment and long-term management of drugs after conservative surgery for endometriosis(EMT).Methods:We searched PubMed,Embase,Medline,Google Scholar,Cochrane Library,China National Knowledge Infrastructure,Wanfang,and Weipu databases from the establishment of the database until December 31,2023 for relevant literature on EMT pharmacotherapy.Meta-analysis was performed using Stata 18.0 software to assess the efficacy of DNG,gonadotropin-releasing hormone agonist(GnRH-a),compound short-acting oral contraceptive(COC)and levonorgestrel intrauterine sustained-release system(LNG-IUS)in reducing the diameter of ovarian endometrioma(OMA),relieving pelvic pain and preventing EMT postoperative recurrence in EMT pa-tients after non-surgical drug treatment and conservative surgery,as well as the adverse reactions of drugs.Re-sults:①During non-surgical medication treatment of EMT,there was no statistically significant difference(P＞0.05)between DNG and GnRH-a in reducing OMA diameter and relieving pelvic pain.Compared with COC,DNG was superior to COC in reducing the diameter of OMA(WMD 10.44 mm,P=0.017)and relieving pelvic pain(WMD 12.20 mm,P＜0.001).②During long-term medication management after conservative EMT surger-y:there was no statistically significant difference(P＞0.05)between DNG,GnRH-a,COC and LNG-IUS in re-ducing postoperative recurrence and controlling pelvic pain significant(P＞0.05).③Adverse drug reactions:com-pared with GnRH-a,DNG had a reduced risk of bone loss(bone density WMD2.78 g/cm3,P=0.038),hot fla-shes(OR 0.07,P＜0.001),and an increased risk of irregular vaginal bleeding(OR 19.10,P＜0.001);com-pared with COC,the risk of weight gain,mood abnormalities,and breast tenderness,nausea and vomiting,and sleep disorders in DNG were reduced(OR＜1,P＜0.05);compared with LNG-IUS,the risk of abnormalities of mood in DNG was increased(OR 9.87,P=0.033).Conclusions:DNG treatment is more effective than COC in non-surgical drug therapy for EMT.When supplemental medication was given after conservative EMT surgery,DNG,like other drugs,can effectively prevent postoperative recurrence and control pelvic pain.The safety of DNG is superior to GnRH-a and COC,slightly inferior to LNG-IUS.

Objective:To compare the efficacy and safety of Dienogest(DNG)with other drugs in non-surgi-cal pharmacologic treatment and long-term management of drugs after conservative surgery for endometriosis(EMT).Methods:We searched PubMed,Embase,Medline,Google Scholar,Cochrane Library,China National Knowledge Infrastructure,Wanfang,and Weipu databases from the establishment of the database until December 31,2023 for relevant literature on EMT pharmacotherapy.Meta-analysis was performed using Stata 18.0 software to assess the efficacy of DNG,gonadotropin-releasing hormone agonist(GnRH-a),compound short-acting oral contraceptive(COC)and levonorgestrel intrauterine sustained-release system(LNG-IUS)in reducing the diameter of ovarian endometrioma(OMA),relieving pelvic pain and preventing EMT postoperative recurrence in EMT pa-tients after non-surgical drug treatment and conservative surgery,as well as the adverse reactions of drugs.Re-sults:①During non-surgical medication treatment of EMT,there was no statistically significant difference(P＞0.05)between DNG and GnRH-a in reducing OMA diameter and relieving pelvic pain.Compared with COC,DNG was superior to COC in reducing the diameter of OMA(WMD 10.44 mm,P=0.017)and relieving pelvic pain(WMD 12.20 mm,P＜0.001).②During long-term medication management after conservative EMT surger-y:there was no statistically significant difference(P＞0.05)between DNG,GnRH-a,COC and LNG-IUS in re-ducing postoperative recurrence and controlling pelvic pain significant(P＞0.05).③Adverse drug reactions:com-pared with GnRH-a,DNG had a reduced risk of bone loss(bone density WMD2.78 g/cm3,P=0.038),hot fla-shes(OR 0.07,P＜0.001),and an increased risk of irregular vaginal bleeding(OR 19.10,P＜0.001);com-pared with COC,the risk of weight gain,mood abnormalities,and breast tenderness,nausea and vomiting,and sleep disorders in DNG were reduced(OR＜1,P＜0.05);compared with LNG-IUS,the risk of abnormalities of mood in DNG was increased(OR 9.87,P=0.033).Conclusions:DNG treatment is more effective than COC in non-surgical drug therapy for EMT.When supplemental medication was given after conservative EMT surgery,DNG,like other drugs,can effectively prevent postoperative recurrence and control pelvic pain.The safety of DNG is superior to GnRH-a and COC,slightly inferior to LNG-IUS.

Objective:To compare the efficacy and safety of Dienogest(DNG)with other drugs in non-surgi-cal pharmacologic treatment and long-term management of drugs after conservative surgery for endometriosis(EMT).Methods:We searched PubMed,Embase,Medline,Google Scholar,Cochrane Library,China National Knowledge Infrastructure,Wanfang,and Weipu databases from the establishment of the database until December 31,2023 for relevant literature on EMT pharmacotherapy.Meta-analysis was performed using Stata 18.0 software to assess the efficacy of DNG,gonadotropin-releasing hormone agonist(GnRH-a),compound short-acting oral contraceptive(COC)and levonorgestrel intrauterine sustained-release system(LNG-IUS)in reducing the diameter of ovarian endometrioma(OMA),relieving pelvic pain and preventing EMT postoperative recurrence in EMT pa-tients after non-surgical drug treatment and conservative surgery,as well as the adverse reactions of drugs.Re-sults:①During non-surgical medication treatment of EMT,there was no statistically significant difference(P＞0.05)between DNG and GnRH-a in reducing OMA diameter and relieving pelvic pain.Compared with COC,DNG was superior to COC in reducing the diameter of OMA(WMD 10.44 mm,P=0.017)and relieving pelvic pain(WMD 12.20 mm,P＜0.001).②During long-term medication management after conservative EMT surger-y:there was no statistically significant difference(P＞0.05)between DNG,GnRH-a,COC and LNG-IUS in re-ducing postoperative recurrence and controlling pelvic pain significant(P＞0.05).③Adverse drug reactions:com-pared with GnRH-a,DNG had a reduced risk of bone loss(bone density WMD2.78 g/cm3,P=0.038),hot fla-shes(OR 0.07,P＜0.001),and an increased risk of irregular vaginal bleeding(OR 19.10,P＜0.001);com-pared with COC,the risk of weight gain,mood abnormalities,and breast tenderness,nausea and vomiting,and sleep disorders in DNG were reduced(OR＜1,P＜0.05);compared with LNG-IUS,the risk of abnormalities of mood in DNG was increased(OR 9.87,P=0.033).Conclusions:DNG treatment is more effective than COC in non-surgical drug therapy for EMT.When supplemental medication was given after conservative EMT surgery,DNG,like other drugs,can effectively prevent postoperative recurrence and control pelvic pain.The safety of DNG is superior to GnRH-a and COC,slightly inferior to LNG-IUS.

Objective:To compare the efficacy and safety of Dienogest(DNG)with other drugs in non-surgi-cal pharmacologic treatment and long-term management of drugs after conservative surgery for endometriosis(EMT).Methods:We searched PubMed,Embase,Medline,Google Scholar,Cochrane Library,China National Knowledge Infrastructure,Wanfang,and Weipu databases from the establishment of the database until December 31,2023 for relevant literature on EMT pharmacotherapy.Meta-analysis was performed using Stata 18.0 software to assess the efficacy of DNG,gonadotropin-releasing hormone agonist(GnRH-a),compound short-acting oral contraceptive(COC)and levonorgestrel intrauterine sustained-release system(LNG-IUS)in reducing the diameter of ovarian endometrioma(OMA),relieving pelvic pain and preventing EMT postoperative recurrence in EMT pa-tients after non-surgical drug treatment and conservative surgery,as well as the adverse reactions of drugs.Re-sults:①During non-surgical medication treatment of EMT,there was no statistically significant difference(P＞0.05)between DNG and GnRH-a in reducing OMA diameter and relieving pelvic pain.Compared with COC,DNG was superior to COC in reducing the diameter of OMA(WMD 10.44 mm,P=0.017)and relieving pelvic pain(WMD 12.20 mm,P＜0.001).②During long-term medication management after conservative EMT surger-y:there was no statistically significant difference(P＞0.05)between DNG,GnRH-a,COC and LNG-IUS in re-ducing postoperative recurrence and controlling pelvic pain significant(P＞0.05).③Adverse drug reactions:com-pared with GnRH-a,DNG had a reduced risk of bone loss(bone density WMD2.78 g/cm3,P=0.038),hot fla-shes(OR 0.07,P＜0.001),and an increased risk of irregular vaginal bleeding(OR 19.10,P＜0.001);com-pared with COC,the risk of weight gain,mood abnormalities,and breast tenderness,nausea and vomiting,and sleep disorders in DNG were reduced(OR＜1,P＜0.05);compared with LNG-IUS,the risk of abnormalities of mood in DNG was increased(OR 9.87,P=0.033).Conclusions:DNG treatment is more effective than COC in non-surgical drug therapy for EMT.When supplemental medication was given after conservative EMT surgery,DNG,like other drugs,can effectively prevent postoperative recurrence and control pelvic pain.The safety of DNG is superior to GnRH-a and COC,slightly inferior to LNG-IUS.

Objective:To compare the efficacy and safety of Dienogest(DNG)with other drugs in non-surgi-cal pharmacologic treatment and long-term management of drugs after conservative surgery for endometriosis(EMT).Methods:We searched PubMed,Embase,Medline,Google Scholar,Cochrane Library,China National Knowledge Infrastructure,Wanfang,and Weipu databases from the establishment of the database until December 31,2023 for relevant literature on EMT pharmacotherapy.Meta-analysis was performed using Stata 18.0 software to assess the efficacy of DNG,gonadotropin-releasing hormone agonist(GnRH-a),compound short-acting oral contraceptive(COC)and levonorgestrel intrauterine sustained-release system(LNG-IUS)in reducing the diameter of ovarian endometrioma(OMA),relieving pelvic pain and preventing EMT postoperative recurrence in EMT pa-tients after non-surgical drug treatment and conservative surgery,as well as the adverse reactions of drugs.Re-sults:①During non-surgical medication treatment of EMT,there was no statistically significant difference(P＞0.05)between DNG and GnRH-a in reducing OMA diameter and relieving pelvic pain.Compared with COC,DNG was superior to COC in reducing the diameter of OMA(WMD 10.44 mm,P=0.017)and relieving pelvic pain(WMD 12.20 mm,P＜0.001).②During long-term medication management after conservative EMT surger-y:there was no statistically significant difference(P＞0.05)between DNG,GnRH-a,COC and LNG-IUS in re-ducing postoperative recurrence and controlling pelvic pain significant(P＞0.05).③Adverse drug reactions:com-pared with GnRH-a,DNG had a reduced risk of bone loss(bone density WMD2.78 g/cm3,P=0.038),hot fla-shes(OR 0.07,P＜0.001),and an increased risk of irregular vaginal bleeding(OR 19.10,P＜0.001);com-pared with COC,the risk of weight gain,mood abnormalities,and breast tenderness,nausea and vomiting,and sleep disorders in DNG were reduced(OR＜1,P＜0.05);compared with LNG-IUS,the risk of abnormalities of mood in DNG was increased(OR 9.87,P=0.033).Conclusions:DNG treatment is more effective than COC in non-surgical drug therapy for EMT.When supplemental medication was given after conservative EMT surgery,DNG,like other drugs,can effectively prevent postoperative recurrence and control pelvic pain.The safety of DNG is superior to GnRH-a and COC,slightly inferior to LNG-IUS.

Objective:To compare the efficacy and safety of Dienogest(DNG)with other drugs in non-surgi-cal pharmacologic treatment and long-term management of drugs after conservative surgery for endometriosis(EMT).Methods:We searched PubMed,Embase,Medline,Google Scholar,Cochrane Library,China National Knowledge Infrastructure,Wanfang,and Weipu databases from the establishment of the database until December 31,2023 for relevant literature on EMT pharmacotherapy.Meta-analysis was performed using Stata 18.0 software to assess the efficacy of DNG,gonadotropin-releasing hormone agonist(GnRH-a),compound short-acting oral contraceptive(COC)and levonorgestrel intrauterine sustained-release system(LNG-IUS)in reducing the diameter of ovarian endometrioma(OMA),relieving pelvic pain and preventing EMT postoperative recurrence in EMT pa-tients after non-surgical drug treatment and conservative surgery,as well as the adverse reactions of drugs.Re-sults:①During non-surgical medication treatment of EMT,there was no statistically significant difference(P＞0.05)between DNG and GnRH-a in reducing OMA diameter and relieving pelvic pain.Compared with COC,DNG was superior to COC in reducing the diameter of OMA(WMD 10.44 mm,P=0.017)and relieving pelvic pain(WMD 12.20 mm,P＜0.001).②During long-term medication management after conservative EMT surger-y:there was no statistically significant difference(P＞0.05)between DNG,GnRH-a,COC and LNG-IUS in re-ducing postoperative recurrence and controlling pelvic pain significant(P＞0.05).③Adverse drug reactions:com-pared with GnRH-a,DNG had a reduced risk of bone loss(bone density WMD2.78 g/cm3,P=0.038),hot fla-shes(OR 0.07,P＜0.001),and an increased risk of irregular vaginal bleeding(OR 19.10,P＜0.001);com-pared with COC,the risk of weight gain,mood abnormalities,and breast tenderness,nausea and vomiting,and sleep disorders in DNG were reduced(OR＜1,P＜0.05);compared with LNG-IUS,the risk of abnormalities of mood in DNG was increased(OR 9.87,P=0.033).Conclusions:DNG treatment is more effective than COC in non-surgical drug therapy for EMT.When supplemental medication was given after conservative EMT surgery,DNG,like other drugs,can effectively prevent postoperative recurrence and control pelvic pain.The safety of DNG is superior to GnRH-a and COC,slightly inferior to LNG-IUS.

Objective:To observe the effects and safety of dienogest on the volume and symptoms of ovarian endometrioma (OMA).Methods:The clinical data of 75 patients with OMA who underwent treatment with dienogest (2 mg/day) at the First Affiliated Hospital of Nanjing Medical University from July 1st 2020 to March 31st 2024 were retrospectively analysed, mainly comparing the changes in the volume of OMA and the visual analogue scale (VAS) scores of endometriosis-related pain before and after the treatment, as well as observing the changes in the blood biological indicators, liver and kidney function, coagulation function and changes in breast.Results:The median cyst volumes of the OMA patients at 3, 6 and 12 months of dienogest treatment were 13.21 cm 3 (volume reduction rate: 36.00%), 8.33 cm 3 (volume reduction rate: 56.00%) and 4.10 cm 3 (volume reduction rate: 77.62%), respectively, which were all significantly decreased from the pre-treatment period (all P<0.05). The VAS scores of pain of the OMA patients at 3, 6 and 12 months of dienogest treatment all were 0 mm. Blood cancer antigen 125 (CA 125) and cancer antigen 19-9 (CA 19-9) levels decreased progressively during treatment (all P<0.05). There were no statistical differences in the coagulation indexes, liver and kidney function indexes of the patients during dienogest treatment compared with those before treatment (all P>0.05). During the follow-up period, there were a few patients with changes in the growth sites or lesion category of the breast nodules, but there were no occurrence of breast cancer or precancerous lesions. Conclusion:Dienogest is effective in reducing OMA volume and alleviating endometriosis-related pain with few adverse effects.