Oral squamous cell carcinoma (OSCC) is a malignant tumor that seriously threatens human health. Its typical biological characteristics include strong local invasiveness, high lymph node metastasis rate, and high recurrence rate after treatment. Hepatocyte growth factor (HGF), cellular-mesenchymal to epithelial transition factor (c-Met), and the HGF/c-Met signaling pathway are involved in the regulation of the occurrence and development of OSCC. HGF and c-Met proteins are overexpressed in OSCC, and multiple studies have suggested that they are significantly associated with the malignant characteristics of tumors and poor prognosis. Furthermore, the abnormal activation of the HGF/c-Met signaling pathway (driven by HGF-dependent autocrine/paracrine or non-dependent mechanisms such as MET gene mutations, amplification, fusion, and protein overexpression) can synergistically promote tumor cell invasion, metastasis, and angiogenesis by activating downstream signaling pathways. However, HGF/c-Met can also mediate immune escape by promoting lactate secretion increase, inducing programmed death ligand 1 (PD-L1) expression upregulation, activating and expanding myeloid-derived suppressor cells, and promoting the proliferation of regulatory T cells (Tregs). In addition, the crosstalk between the HGF/c-Met signaling pathway and key pathways such as phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT), epidermal growth factor receptor (EGFR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT3), and non-coding RNAs can also promote tumor progression. Currently, three types of targeted drugs have been developed targeting the HGF/c-Met pathway: HGF monoclonal antibody, c-Met monoclonal antibody, and tyrosine kinase inhibitors. Some of these drugs have entered clinical trials. However, the emergence of drug resistance during treatment, especially the bidirectional compensatory activation of alternative signaling pathways such as EGFR, has become a major challenge in clinical practice. This article aims to provide an in-depth analysis of the mechanism of action of the HGF/c-Met pathway in OSCC and its interaction with other pathways, and to review the current research status of existing therapeutic drugs. The aim is to provide an important theoretical basis for developing more effective combined treatment strategies and achieving individualized precise treatment, ultimately improving the clinical prognosis and quality of life of patients.

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.

Objective To investigate the protective effect of arbutin against CCl4-induced hepatic fibrosis in mice and explore the underlying mechanisms. Methods Twenty-four C57BL/6 mice were randomly divided into control group, model group, and low-and high-dose arbutin treatment (25 and 50 mg/kg, respectively) groups. Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4, and arbutin was administered daily via gavage for 6 weeks. After the treatments, serum biochemical parameters of the mice were tested, and liver tissues were taken for HE staining, Sirius Red staining and immunohistochemical staining. RT-qPCR was used to detect the mRNA levels of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-α, and Western blotting was performed to detect α-SMA protein expression in the liver tissues. In the cell experiment, the effect of arbutin treatment for 24 h on THP-1 and RAW264.7 cell migration and recruitment was examined using Transwell migration assay and DAPI staining; The changes in protein levels of Akt, p65, Smad3, p-Akt, p-p65, p-Smad3 and α-SMA in arbutin-treated LX-2 cells were detected with Western blotting. Results Arbutin treatment significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels, alleviated liver tissue damage and collagen deposition, and reduced macrophage infiltration and α-SMA protein expression in the liver of the mouse models (P<0.05 or 0.001). Arbutin treatment also significantly reduced CCl4-induced elevation of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-α mRNA levels in mice (P<0.05). In the cell experiment, arbutin treatment obviously inhibited migration and recruitment of THP-1 and RAW264.7 cells and lowered the phosphorylation levels of Akt, p65 and Smad3 and the protein expression level of α-SMA in LX-2 cells. Conclusion Arbutin ameliorates liver inflammation and fibrosis in mice by inhibiting hepatic stellate cell activation via reducing macrophage recruitment and infiltration and suppressing activation of the Akt/NF-κB and Smad signaling pathways.

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.