Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Objective To explore the effect of exenatide on oxidative stress in the hypothalamus of diabetes mice and its potential mechanism.Methods After one week of adaptive feeding,C57BL/6J mice were randomly divided into the CON group(normal chaw diet),the T2DM group(high-fat diet,HFD),and the T2DM+Exe group(HFD+exenatide).After 8 weeks of HFD,mice in the T2DM+Exe group were intraperitoneally injected with exenatide[24 nmol/(kg·d)]for 8 weeks.The weight and glucose and lipid metabolism levels of the mice were measured,and the levels of inflammatory and adipokine factors in mice were detected using the ELISA method.Western Blot was used to detect the expression of melanocortin receptor-4(MC4R)and proopiomelanocor-tin(POMC)in the hypothalamus.Hypothalamic mitochondria were extracted,and the content of mitochondrial reactive oxygen species(ROS)was measured using a flow cytometer.The content of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)in the mitochondria were detected using assay kits.Changes in the ultrastructure of mitochondria were observed using a transmission electron microscope.In vitro experiments,pal-mitic acid(PA)and exenatide were used to treat hypothalamic GT1-7 cells,and short hairpin RNA(shRNA)was used to silence the melanocortin 4 receptor(MC4R),and observe the cellular oxidative stress and lipid deposition.Results Compared with the CON group,the T2DM group mice showed a significant increase in glucose and lipid metabolism indicators,pro-inflammatory factors,and adipose factor levels(P<0.05),the expression of MC4R and POMC proteins in the hypothalamus were decreased(P<0.05),and the mitochondrial ROS and MDA content in the hypothalamus significantly were increased(P<0.05),while SOD and CAT activities were decreased(P<0.05).Mitochondrial morphology was abnormal.After intervention with exenatide,the above indicators were signifi-cantly improved.After inhibiting MC4R expression in vitro experiments,compared with the intervention group with exenatide,the ROS and MDA content was significantly increased(P<0.05),SOD activity was decreased(P<0.05),and lipid deposition occurred in the cells.Conclusions Exenatide exhibits a protective effect on hypotha-lamic oxidative stress injury in diabetic mice,and this mechanism may be associated with the upregulation of MC4R expression.

Objective:To investigate the clinical results of gasless endoscopic thyroidectomy via posterior chest-collarbone approach (GETPCA) compared with open neck surgery for papillary thyroid carcinoma (PTC) .Mthods:Retrospective analysis of PTC patients admitted to the Department of Thyroid and Breast Surgery of the Third Affiliated Hospital of Anhui Medical University from Jan. 2022 to Dec. 2023,and randomly divided into the open group and the lumbo-scopic group according to whether or not they had a requirement for an unmarked neck, in which the open group was n=100,and the lumbo-scopic group was n=67,with 39 male cases and 128 female cases. Clinicopathological characteristics, surgery-related indexes, postoperative complications, postoperative pain scores and postoperative cosmetic satisfaction were compared between the two groups.The t-test,Wilcoxon rank-sum test, χ2 test, consecutively corrected χ2 test, or Fisher’s exact probability method were used to compare the groups. Results:No recurrence was seen during the follow-up period,and none of the cases in the luminal group was open in the middle. The differences in age, body mass index BMI, gender, relative tumor location,preoperative TSH, T stage and N stage between the two groups were not statistically significant ( P>0.05) . The total operation time [ (121.07±39.80) min vs. (93.87±26.97) min]in the luminal group was greater than that in the open group,intraoperative bleeding was less than that in the open group, and the postoperative drainage flow[ (130.69±31.01) mL vs. (105.52±32.71) mL] was greater than that in the open group in the postoperative period of 72 h, and the difference was statistically significant ( P<0.001) .There was no statistical difference between the two groups in terms of 24-h postoperative drainage volume, number of central zone lymph node dissection, number of positive central zone lymph nodes,postoperative hospitalization days or total hospitalization cost ( P>0.05) .The number of cases of neck discomfort (3 cases vs.23 cases, P<0.001) and swallowing dysfunction (2 cases vs.20 cases, P=0.003) in the luminal group was smaller than that in the open group,and the difference was statistically significant.The difference in the incidence of bleeding,incision infection,seroma,temporary recurrent laryngeal nerve injury and temporary parathyroid gland injury between the two groups was also not statistically significant ( P>0.05) .The postoperative NRS on day 1 and postoperative NRS on day 3 of the luminal group were lower than those of the open group,and the difference was statistically significant ( P>0.05) ,while there was no statistically significant difference between the postoperative NRS on day 7,the postoperative NRS on month 1 and the postoperative NRS on month 3 ( P>0.05) .Cosmetic satisfaction at 6 months postoperatively was higher in the luminal group than in the open group,and the difference was statistically significant ( P<0.001) . Conclusion:GETPCA for the treatment of the PTC is safe and feasible,with satisfactory cosmetic results and reduction of neck discomfort and swallowing dysfunction,which is worthy of clinical popularization.

Objective:To investigate the clinical results of gasless endoscopic thyroidectomy via posterior chest-collarbone approach (GETPCA) compared with open neck surgery for papillary thyroid carcinoma (PTC) .Mthods:Retrospective analysis of PTC patients admitted to the Department of Thyroid and Breast Surgery of the Third Affiliated Hospital of Anhui Medical University from Jan. 2022 to Dec. 2023,and randomly divided into the open group and the lumbo-scopic group according to whether or not they had a requirement for an unmarked neck, in which the open group was n=100,and the lumbo-scopic group was n=67,with 39 male cases and 128 female cases. Clinicopathological characteristics, surgery-related indexes, postoperative complications, postoperative pain scores and postoperative cosmetic satisfaction were compared between the two groups.The t-test,Wilcoxon rank-sum test, χ2 test, consecutively corrected χ2 test, or Fisher’s exact probability method were used to compare the groups. Results:No recurrence was seen during the follow-up period,and none of the cases in the luminal group was open in the middle. The differences in age, body mass index BMI, gender, relative tumor location,preoperative TSH, T stage and N stage between the two groups were not statistically significant ( P>0.05) . The total operation time [ (121.07±39.80) min vs. (93.87±26.97) min]in the luminal group was greater than that in the open group,intraoperative bleeding was less than that in the open group, and the postoperative drainage flow[ (130.69±31.01) mL vs. (105.52±32.71) mL] was greater than that in the open group in the postoperative period of 72 h, and the difference was statistically significant ( P<0.001) .There was no statistical difference between the two groups in terms of 24-h postoperative drainage volume, number of central zone lymph node dissection, number of positive central zone lymph nodes,postoperative hospitalization days or total hospitalization cost ( P>0.05) .The number of cases of neck discomfort (3 cases vs.23 cases, P<0.001) and swallowing dysfunction (2 cases vs.20 cases, P=0.003) in the luminal group was smaller than that in the open group,and the difference was statistically significant.The difference in the incidence of bleeding,incision infection,seroma,temporary recurrent laryngeal nerve injury and temporary parathyroid gland injury between the two groups was also not statistically significant ( P>0.05) .The postoperative NRS on day 1 and postoperative NRS on day 3 of the luminal group were lower than those of the open group,and the difference was statistically significant ( P>0.05) ,while there was no statistically significant difference between the postoperative NRS on day 7,the postoperative NRS on month 1 and the postoperative NRS on month 3 ( P>0.05) .Cosmetic satisfaction at 6 months postoperatively was higher in the luminal group than in the open group,and the difference was statistically significant ( P<0.001) . Conclusion:GETPCA for the treatment of the PTC is safe and feasible,with satisfactory cosmetic results and reduction of neck discomfort and swallowing dysfunction,which is worthy of clinical popularization.

Objective To explore the effect of exenatide on oxidative stress in the hypothalamus of diabetes mice and its potential mechanism.Methods After one week of adaptive feeding,C57BL/6J mice were randomly divided into the CON group(normal chaw diet),the T2DM group(high-fat diet,HFD),and the T2DM+Exe group(HFD+exenatide).After 8 weeks of HFD,mice in the T2DM+Exe group were intraperitoneally injected with exenatide[24 nmol/(kg·d)]for 8 weeks.The weight and glucose and lipid metabolism levels of the mice were measured,and the levels of inflammatory and adipokine factors in mice were detected using the ELISA method.Western Blot was used to detect the expression of melanocortin receptor-4(MC4R)and proopiomelanocor-tin(POMC)in the hypothalamus.Hypothalamic mitochondria were extracted,and the content of mitochondrial reactive oxygen species(ROS)was measured using a flow cytometer.The content of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)in the mitochondria were detected using assay kits.Changes in the ultrastructure of mitochondria were observed using a transmission electron microscope.In vitro experiments,pal-mitic acid(PA)and exenatide were used to treat hypothalamic GT1-7 cells,and short hairpin RNA(shRNA)was used to silence the melanocortin 4 receptor(MC4R),and observe the cellular oxidative stress and lipid deposition.Results Compared with the CON group,the T2DM group mice showed a significant increase in glucose and lipid metabolism indicators,pro-inflammatory factors,and adipose factor levels(P<0.05),the expression of MC4R and POMC proteins in the hypothalamus were decreased(P<0.05),and the mitochondrial ROS and MDA content in the hypothalamus significantly were increased(P<0.05),while SOD and CAT activities were decreased(P<0.05).Mitochondrial morphology was abnormal.After intervention with exenatide,the above indicators were signifi-cantly improved.After inhibiting MC4R expression in vitro experiments,compared with the intervention group with exenatide,the ROS and MDA content was significantly increased(P<0.05),SOD activity was decreased(P<0.05),and lipid deposition occurred in the cells.Conclusions Exenatide exhibits a protective effect on hypotha-lamic oxidative stress injury in diabetic mice,and this mechanism may be associated with the upregulation of MC4R expression.

BACKGROUND:Sema3A is a power secretory osteoprotective factor.However,studies about Sema3A-modified dental pulp stem cells(Sema3A-DPSCs)are rare. OBJECTIVE:To explore the osteogenic differentiation ability of Sema3A-DPSCs and their regulatory effect on the osteogenic differentiation of the pre-osteoblast cell line MC3T3-E1. METHODS:First,Sema3A-DPSCs were constructed using a lentivirus infection system carrying the Sema3A gene.Control lentivirus-treated DPSCs(Vector-DPSCs)were used as controls.Sema3A-DPSCs or Vector-DPSCs were co-cultured with proosteoblast line MC3T3-E1 at the ratio of 1∶1 and 1∶3 for 24 hours.Finally,the Sema3A-DPSCs,Vector-DPSCs and their co-cultured cells with MC3T3-E1 were cultured for osteogenic induction and differentiation.Osteogenic gene expression was detected by alkaline phosphatase staining,alizarin red staining and real-time quantitative RT-PCR to evaluate osteogenic differentiation ability. RESULTS AND CONCLUSION:(1)Sema3A mRNA and protein expression levels in Sema3A-DPSCs were significantly up-regulated.The level of secreted Sema3A in cell supernatant was up-regulated.(2)Compared with the Vector-DPSCs,mRNA expressions of osteogenic genes alkaline phosphatase,Runt-related transcription factor 2,osteocalcin and Sp7 transcription factors in Sema3A-DPSCs were up-regulated;the activity of alkaline phosphatase was enhanced,and the formation of mineralized nodules increased.(3)There were no obvious differences in proliferation between Sema3A-DPSCs and Vector-DPSCs.(4)Compared with MC3T3-E1/Vector-DPSCs co-culture system,the expression of MC3T3-E1 osteogenic genes was up-regulated,and the total alkaline phosphatase activity was enhanced and more mineralized nodules were formed in the MC3T3-E1/Sema3A-DPSCs co-culture system.(5)The results suggest that overexpression of Sema3A can enhance the osteogenic differentiation of DPSCs.Overexpression of Sema3A in DPSCs can promote osteogenic differentiation of MC3T3-E1 in the DPSCs/MC3T3-E1 co-culture system.

Objective:To observe the effect of shift work on the stability of the circadian clock and insulin sensitivity in non-overweight/obese individuals with normal blood glucose, and explore underlying connection.Methods:Female shift working nurses in the Department of Blood Transplantation and non-shift working nurses in the Health Management Center in the First Affiliated Hospital of Zhengzhou University were divided into shift worker group (SW group) and non-shift worker group (NSW group). Serum inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α)], adipokines (adiponectin, leptin, chemerin, visfatin), and melatonin levels were measured using enzyme linked immunosorbent assay (ELISA). Realtime fluorescence quantitative PCR was performed to detect peripheral blood circadian clock genes circadian locomotor output cycles protein kaput(Clock) and brain and muscle ARNT-like protein 1(Bmal1). Cortisol and fasting insulin were measured by chemiluminescent microparticle immunoassay, and HbA 1C was measured by capillary electrophoresis. In addition, visceral fat area (VFA) was assessed with bioelectrical impedance analyzer, and mid-sleep time composite phase deviations (CPD) was calculated based on the International Physical Activity Short Questionnaire. Results:SW group had lower serum level of melatonin ( P=0.023) and higher cortisol ( P=0.001) than the NSW group, and altered mRNA expression of Clock and Bmal1 ( P=0.034, P=0.047). Fasting blood glucose and HbA 1C in the SW group, although in the normal range, had been higher than in the NSW group ( P=0.011, P=0.033). Although body mass index was normal in SW group, VFA had been higher than that of the NSW group ( P=0.010). And homeostasis model assessment for insulin resistance (HOMA-IR), IL-6, TNF-α, leptin, chemerin, and visfatin were significantly higher in the SW group than NSW group ( P=0.033, P=0.012, P=0.001, P=0.011, P=0.021, P=0.007). In addition, adjusting for body mass index and activity factors revealed a significant positive correlation between CPD and VFA ( r=0.434, P=0.049), inflammatory factors IL-6 ( r=0.514, P=0.017) and TNF-α ( r=0.700, P<0.001) and pro-inflammatory adipokines leptin ( r=0.473, P=0.030), chemerin ( r=0.439, P=0.047), visfatin ( r=0.521, P=0.015). Conclusion:Shift work can affect circadian clock, with increased visceral adiposity, pro-inflammatory adipokines, inflammatory factors and decreased insulin sensitivity in women without overweight/obese.

Objective:To observe the effects of continuous light exposure on skeletal muscle fiber type transformation and lipid metabolism, and to explore its internal relationship.Methods:Mice were randomly divided into normal light group and 24-hour continuous light group by random number table. The serum and skeletal muscle lipid content and urine 6-sulfatoxymelatonin(6-SML)level were detected by ELISA. The expression of circadian clock and lipid metabolism related genes mRNA were observed by realtime PCR. The muscle fiber type and lipid deposition were evaluated by tissue immunofluorescence as well as oil red O staining.Results:Compared with the normal light group, the level of 6-SML in urine at night decreased( P<0.05), and the expression level and rhythm of brain and muscle ARNT-like protein 1(Bmal1), circadian locomotor output cycles protein kaput(Clock), and period 2(Per2)mRNA in the skeletal muscle changed in continuous light group. In addition, the body weight, blood lipid, free fatty acid, and triglyceride contents of skeletal muscle in continuous light group increased significantly( P<0.05 or P<0.01), the expression of carnitine palmitoyltransferase 1b (Cpt1b)mRNA, the key enzyme of fatty acid oxidation, decreased significantly( P<0.05), while the expression of stearoyl-CoA desaturase(Scd1)mRNA, a lipid synthesis related gene, increased significantly( P<0.01). Further immunofluorescence analysis showed that the proportion of slow muscle fibers decreased and that of fast muscle fibers increased in continuous light group(both P<0.05). Conclusion:The process of ectopic deposition of lipid in skeletal muscle in mice induced by continuous light exposure may be related to the remodeling of skeletal muscle fibers.

Objective To explore the value ofspatio-temporal image correlation (STIC) technique in diagnosis of fetal ductus arteriosus aneurysm (DAA).Methods A total of 67 pregnant women,diagnosed with fetal ductus arteriosus aneurysm,were selected from the Fourth Affiliated Hospital of Harbin Medical University,between September 2014 and September 2016.2DE and STIC techniques were used to observe the form of fetal ductus arteriosus aneurysm.STIC technique was used to measure the maximum diameter,minimum diameter,systolic peak velocity,and diastolic velocity of ductus arteriosus aneurysm in 40 cases caused by ductus arteriosus stenosis.Pearson linear correlation analysis was applied to analyze the correlation between the maximum diameter and the minimum diameter,systolic peak velocity and diastolic velocity.The maximum diameters of 67 ductus arteriosus aneurysm were measured by 2DE and STIC techniques,and the above measurements were repeated one week later.ICC was used to analyze the consistency between 2DE and STIC technique,and internal consistency of 2DE and STIC technique,respectively.Results Pearson linear correlation analysis showed that the maximum diameter of the DAA was negatively correlated with the minimum diameter (r=-0.755,P ＜ 0.001) significantly,and positively correlated with the systolic peak velocity (r=0.779,P ＜ 0.001) significantly.The internal consistency of STIC technique was the best of the three,followed by the consistency between 2DE and STIC techniques,with the 2DE,illustrating the lowest consistency.Conclusions STIC technique provides with more comprehensive and accurate volume data than 2DE in the diagnosis of fetal ductus arteriosus aneurysm.Thus,this technique is conducive to the early detection of ductus arterious stenosis,observation of hemodynamic changes,closely monitoring of relevant indicators to guide clinical timely intervention,and to improve the quality of life of children.