Breast cancer has become the malignant tumor with the highest incidence rate among women， seriously threatening the life and health of women all over the world. The pathogenic factors and development mechanisms of breast cancer are complex and diverse. The development of breast cells from ordinary hyperplasia to atypical hyperplasia， and from pre-cancerous lesions to cancerous lesions， is a long-term progressive process. Therefore， early screening and prevention of breast cancer is particularly important. Western medicine has a relatively mature treatment program for breast cancer， which is mainly based on surgery and systemic treatment， whereas the ensuing complications and adverse reactions often bring a heavy burden to patients. For the precancerous lesions of breast cancer， surgery is also the mainstay of treatment. In recent years， traditional Chinese medicine （TCM） has increasingly highlighted its advantages in the prevention and treatment of breast cancer. Increasing studies have shown that in the prevention and treatment of breast cancer and pre-cancerous lesions， TCM compound prescriptions， single herbs or herb pairs， and active components are able to regulate a variety of intracellular signaling pathways through multi-targets to inhibit the proliferation and invasion， promote the apoptosis and autophagy of tumor cells， and regulate the cell cycle and the immune microenvironment， thus exerting anti-tumor effects. At the same time， they can significantly attenuate the toxic side effects of radiotherapy and drug resistance of patients. However， the specific mechanisms of TCM in the prevention and treatment of breast cancer and precancerous lesions have not been fully clarified. The available studies are tanglesome regarding the TCM inhibition of tumor development through the regulation of classical signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Wnt/β-catenin， and Notch， which still need to be verified by a large number of clinical and experimental studies. Therefore， this paper reviews the research progress in the prevention and treatment of breast cancer and precancerous lesions by TCM through interfering with the relevant signaling pathways in recent years， aiming to summarize the possible mechanisms of TCM in the prevention and treatment of breast cancer and provide references for subsequent studies.

Objective:To investigate the clinical efficacy of intraoperative regional lymph-adenectomy and extended lymphadenectomy in resectable hilar cholangiocarcinoma.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 187 patients of hilar cholangiocarcinoma who were admitted to Henan University People′s Hospital from January 2014 to January 2018 were collected. There were 105 males and 82 females, aged (57±9)years. Of the 187 patients, 62 patients undergoing hilar cholangiocarcinoma resection with extended lymphadenectomy were divided into the extended group, and 125 patients under-going hilar cholangiocarcinoma resection with regional lymphadenectomy were divided into the regional group. Observation indicators:(1) propensity score matching status and comparison of clinical data of patients between the two groups after matching; (2) intraoperative and postoperative conditions; (3) follow-up. Comparison of measurement data with normal distribu-tion between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. The Kaplan-Meier method was used to plot calculate survival rate and survival curve. The Log-rank test was used for survival analysis. Propen-sity score matching was performed using the 1∶1 nearest neighbor matching method, with the caliper value of 0.1. Results:(1) Propen-sity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 187 patients, 104 patients were success-fully matched, with 52 cases in each of the extended group and the regional group. After propensity score matching, the elimination of tumor diameter, neural invasion, Bismuth classification, and TNM staging confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After pro-pensity score matching, the operation time of the extended group was (341±83)minutes, the number of lymph node dissected was 12.3±4.5, the number of positive lymph node dissected was 2.2±0.7, cases of postoperative new lymphadenectasis was 17. The above indicators of the regional group were (311±73)minutes, 9.2±3.4, 1.5±0.5, 44, respectively. There were significant differences in the above indica-tors between patients of the two groups ( t=-1.99, -3.92, -5.57, χ2=31.18, P<0.05). (3) Follow-up. After propensity score matching, all 104 patients were followed up after surgery, with the follow-up time of 29(range, 3-49)months. The postoperative 3-year overall survival rate was 44.2% of the extended group, versus 30.8% of the regional group, showing a significant difference between the two groups ( χ2=4.41, P<0.05). Conclusions:The perioperative safety of regional lymphadenec-tomy and extended lymphadenectomy in the radical resection of hilar cholangiocarcinoma are com-parable. Extended lymphadenectomy can increase the number of positive lymph node detected and improve the postoperative survival rate of patients.

Objective To investigate the clinical effect of hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of mixed hemorrhoids with annular prolapse.Methods A retrospective analysis was conducted to select 80 patients with annular prolapse mixed hemorrhoids admitted to the anorectal Department of our hospital from January 2022 to April 2023.According to different treatment plans,they were divided into control group(n=40 cases)who received external stripping and internal ligation combined with tape ligation,and study group(n=40 cases)who received hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligation and suspension.The operative effect,operative status,postoperative anal pain,anal edema,stool blood score and quality of life were evaluated.Results The effective rate of the study group was 97.50％,which was higher than that of the control group(77.50％)(P＜0.05).The operation time,intraoperative blood loss,hospital stay and wound healing time of the research group were(25.03±10.00)minutes,(10.00±5.32)ml,(7.25±1.54)days and(12.21±2.00)days respectively.[is better than that of control group(29.85±14.00)minutes,ml(17.85±10.25),(11.87±2.35),(18.89±4.85)days],two groups of comparison,the difference was statistically significant(P＜0.05).The VAS scores of anal pain in the study group on 1 day,3 days and 7 days after the operation were(4.25±0.85)points,(2.89±0.54)points and(2.00±0.30)points,respectively.The scores of perianal edema were(1.87±0.36)points,(1.41±0.30)points,and(1.00±0.20)points,respectively.The hematochezia scores were(1.85±0.21)points,(1.34±0.18)points,and(0.85±0.13)points,respectively.Which were better than that of control group[(7.56±1.10),(6.54±1.03),(4.87±1.00)][(2.40±0.58),(2.03±0.49),(1.87±0.45)][(2.45±0.55),(2.03±0.47),(1.88±0.25)],and the differences were statistically significant(P＜0.05).The recurrence rate was 2.50％in the study group and 17.50％in the control group(P＜0.05).The scores of SF,MH,PF and GH of the Modified Health Survey Summary Form(SF-36)in the study group were(88.54±10.22,87.87±10.58,88.97±10.00,89.95±10.05)higher than those of the control group(67.52±10.00,70.10±11.25,71.10±9.85,70.00±10.00)(P＜0.05).Conclusion Hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of patients with annular prolapse mixed hemorrhoids has ideal surgical effect and little trauma,which is beneficial to promoting postoperative rehabilitation,alleviating anal pain,improving anal edema and hematostoecium,and improving quality of life.

Objective:To investigate the clinical efficacy of intraoperative regional lymph-adenectomy and extended lymphadenectomy in resectable hilar cholangiocarcinoma.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 187 patients of hilar cholangiocarcinoma who were admitted to Henan University People′s Hospital from January 2014 to January 2018 were collected. There were 105 males and 82 females, aged (57±9)years. Of the 187 patients, 62 patients undergoing hilar cholangiocarcinoma resection with extended lymphadenectomy were divided into the extended group, and 125 patients under-going hilar cholangiocarcinoma resection with regional lymphadenectomy were divided into the regional group. Observation indicators:(1) propensity score matching status and comparison of clinical data of patients between the two groups after matching; (2) intraoperative and postoperative conditions; (3) follow-up. Comparison of measurement data with normal distribu-tion between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. The Kaplan-Meier method was used to plot calculate survival rate and survival curve. The Log-rank test was used for survival analysis. Propen-sity score matching was performed using the 1∶1 nearest neighbor matching method, with the caliper value of 0.1. Results:(1) Propen-sity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 187 patients, 104 patients were success-fully matched, with 52 cases in each of the extended group and the regional group. After propensity score matching, the elimination of tumor diameter, neural invasion, Bismuth classification, and TNM staging confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After pro-pensity score matching, the operation time of the extended group was (341±83)minutes, the number of lymph node dissected was 12.3±4.5, the number of positive lymph node dissected was 2.2±0.7, cases of postoperative new lymphadenectasis was 17. The above indicators of the regional group were (311±73)minutes, 9.2±3.4, 1.5±0.5, 44, respectively. There were significant differences in the above indica-tors between patients of the two groups ( t=-1.99, -3.92, -5.57, χ2=31.18, P<0.05). (3) Follow-up. After propensity score matching, all 104 patients were followed up after surgery, with the follow-up time of 29(range, 3-49)months. The postoperative 3-year overall survival rate was 44.2% of the extended group, versus 30.8% of the regional group, showing a significant difference between the two groups ( χ2=4.41, P<0.05). Conclusions:The perioperative safety of regional lymphadenec-tomy and extended lymphadenectomy in the radical resection of hilar cholangiocarcinoma are com-parable. Extended lymphadenectomy can increase the number of positive lymph node detected and improve the postoperative survival rate of patients.

Objective To investigate the clinical effect of hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of mixed hemorrhoids with annular prolapse.Methods A retrospective analysis was conducted to select 80 patients with annular prolapse mixed hemorrhoids admitted to the anorectal Department of our hospital from January 2022 to April 2023.According to different treatment plans,they were divided into control group(n=40 cases)who received external stripping and internal ligation combined with tape ligation,and study group(n=40 cases)who received hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligation and suspension.The operative effect,operative status,postoperative anal pain,anal edema,stool blood score and quality of life were evaluated.Results The effective rate of the study group was 97.50％,which was higher than that of the control group(77.50％)(P＜0.05).The operation time,intraoperative blood loss,hospital stay and wound healing time of the research group were(25.03±10.00)minutes,(10.00±5.32)ml,(7.25±1.54)days and(12.21±2.00)days respectively.[is better than that of control group(29.85±14.00)minutes,ml(17.85±10.25),(11.87±2.35),(18.89±4.85)days],two groups of comparison,the difference was statistically significant(P＜0.05).The VAS scores of anal pain in the study group on 1 day,3 days and 7 days after the operation were(4.25±0.85)points,(2.89±0.54)points and(2.00±0.30)points,respectively.The scores of perianal edema were(1.87±0.36)points,(1.41±0.30)points,and(1.00±0.20)points,respectively.The hematochezia scores were(1.85±0.21)points,(1.34±0.18)points,and(0.85±0.13)points,respectively.Which were better than that of control group[(7.56±1.10),(6.54±1.03),(4.87±1.00)][(2.40±0.58),(2.03±0.49),(1.87±0.45)][(2.45±0.55),(2.03±0.47),(1.88±0.25)],and the differences were statistically significant(P＜0.05).The recurrence rate was 2.50％in the study group and 17.50％in the control group(P＜0.05).The scores of SF,MH,PF and GH of the Modified Health Survey Summary Form(SF-36)in the study group were(88.54±10.22,87.87±10.58,88.97±10.00,89.95±10.05)higher than those of the control group(67.52±10.00,70.10±11.25,71.10±9.85,70.00±10.00)(P＜0.05).Conclusion Hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of patients with annular prolapse mixed hemorrhoids has ideal surgical effect and little trauma,which is beneficial to promoting postoperative rehabilitation,alleviating anal pain,improving anal edema and hematostoecium,and improving quality of life.

Objective: To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved, specifically focusing on the role of the caspase-3/gasdermin E (GSDME) signaling pathway and the impact of endoplasmic reticulum (ER) stress and autophagy. Methods: Necrostatin-1 (Nec-1), lactate dehydrogenase release (LDH) assay, and Hoechst/propidium iodide (PI) double staining were employed to validate the mode of cell death. Western blot was used to detect the cleavage of GSDME and the expression of light chain 3 (LC3) and BIP. Results: Celastrol induced cell swelling with large bubbles, which is consistent with the pyroptotic phenotype. Moreover, treatment with celastrol induced GSDME cleavage, indicating the activation of GSDME-mediated pyroptosis. GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells. In addition, cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells, suggesting that GSDME activation was induced by caspase-3. Mechanistically, celastrol induced endoplasmic reticulum (ER) stress and autophagy in HeLa cells, and other ER stress inducers produced effects consistent with those of celastrol. Conclusion These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress, which may shed light on the potential antitumor clinical applications of celastrol.

Objective:To explore the differences in bacterial community structure between proximal colon cancer (PC), distal colon cancer (DC), and rectal cancer (RC), and the values of featured microbiota in differentiating PC with tumor markers.Methods:This case-control study enrolled 85 newly diagnosed colorectal cancer patients, including 22 PC, 15 DC and 48 RC patients, and 8 colorectal adenoma patients from May 2019 to July 2022 at the Department of General Surgery, Anyang Oncology Hospital. The blood and fecal samples were collected before surgery and then subjected to biochemical tests for tumor markers and 16S rDNA tests, respectively. SPSS (27.0.1) was applied to perform the t-test, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and Chi-Squared Test. Also, the receiver operating characteristic curve (ROC) was plotted on tumor markers and/or f_Bacteroidaceae with SPSS software .Results:All groups had significant differences in the CA125 ( F=3.543, P<0.05), CA72-4 ( F=3.596, P<0.05), and serum tumor-associated materials (TAM) levels ( F=5.787, P<0.01). In PC group, the levels of CA125 [PC vs RC, (36.84±6.30) kU/L vs (12.73±4.21) kU/L, P<0.01] and CA72-4 [PC vs RC, (45.56±10.86) kU/L vs (3.30±7.63) kU/L, P<0.01] were significantly higher than that of the RC group, while the level of TAM was remarkably elevated in PC group than in RC group [PC vs RC, (124.84±5.19) U/ml vs (102.44±3.63) U/ml, P<0.001] and CRA group [PC vs CRA, (124.84±5.19) U/ml vs (95.39±8.42) U/ml, P<0.01]. The LEfSe analysis showed that the featured microbiota in the PC group included f_Bacteroidaceae, f_Neisseriaceae, f_Clostridiaceae_1, f_Spirochaetaceae, and so on. The largest area under the ROC belonged to the combination of TAM and f_Bacteroidaceae, which reached 0.845 (95% CI 0.747-0.944), with sensitivity being 0.857 and specificity being 0.815. Conclusions:There is heterogeneity in gut microbiota composition among PC, DC, RC, and CRA. The combination of gut microbiota and tumor biomarkers demonstrated good differentiating effects in proximal colon cancers.

Objective Kisspeptin,a protein encoded by the KISS1 gene,functions as an essential factor in suppressing tumor growth.The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway,which assumes a central role in maintaining cellular homeostasis.In the specific context of this investigation,the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization.This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway,aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion(RSA).Methods We enrolled a cohort comprising 45 individuals diagnosed with RSA,who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020.On the other hand,an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included.To comprehensively assess the molecular landscape,Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin(and its gene KISS1),IGFBP1(an established marker of decidualization),Notch1,Akt,and Foxo1 within the decidua.Human endometrial stromal cells(hESC)were given targeted interventions,including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10(the bioactive fragment of kisspeptin),and were subsequently designated as the siKP group or the KP10 group,respectively.A control group comprised hESC was transfected with blank siRNA,and cell proliferation was meticulously evaluated with CCK8 assay.Following in vitro induction for decidualization across the three experimental groups,immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups.Furthermore,RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1,Notch1,Akt,and Foxo1 across the three cell groups.Subsequently,decidualization was induced in hESC by adding inhibitors targeting Notch1,Akt,and Foxo1.The expression profiles of the aforementioned proteins and genes in the four groups were then examined,with hESC induced for decidualization without adding inhibitors serving as the normal control group.To establish murine models of normal pregnancy(NP)and RSA,CBA/J×BALB/c and CBA/J×DBA/2 mice were used.The mice were respectively labeled as the NP model and RSA model.The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234(acting as a blocker)and were designated as RSA-KP10 and NP-KP234 groups.On the other hand,the control groups received intraperitoneal injections of normal saline(NS)and were referred to as RSA-NS and NP-NS groups.Each group comprised 6 mice,and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes.Results The analysis revealed that the expression levels of kisspeptin,IGFBP1,Notch1,Akt,and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP(P<0.01 for kisspeptin and P<0.05 for IGFBP1,Notch1,Akt,and Foxo1).After the introduction of kisspeptin10 to hESC,there was an observed enhancement in decidualization capability.Subsequently,the expression levels of Notch1,Akt,and Foxo1 showed an increase,but they decreased after interference with KISS1.Through immunofluorescence analysis,it was observed that proliferative hESC displayed a slender morphology,but they transitioned to a rounder and larger morphology post-decidualization.Concurrently,the expression of Notch1 increased,suggesting enhanced decidualization upon the administration of kisspeptin10,but the expression decreased after interference with KISS1.Further experimentation involved treating hESC with inhibitors specific to Notch1,Akt,and Foxo1 separately,revealing a regulatory sequence of Notch1/Akt/Foxo1(P<0.05).In comparison to the NS group,NP mice administered with kisspeptin234 exhibited increased fetal absorption rates(P<0.001)and decreased expression of IGFBP1,Notch1,Akt,and Foxo1(P<0.05).Conversely,RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates(P<0.001)and increased expression levels of the aforementioned molecules(P<0.05).Conclusion It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade.A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization,which in turn might contribute to the development or progression of RSA.

Objective:To analyze the effect of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) after laparoscopic radical resection.Methods:Clinical data of 165 patients with HCC undergoing laparoscopic radical resection in Henan University People's Hospital from January 2018 to December 2021 were retrospectively analyzed, including 122 males and 43 females, aged (55.5±11.4) years. Patients were divided into sarcopenia group ( n=79) and control group (non-sarcopenia, n=86) according to the skeletal muscle index. The survivals were analyzed using the Kaplan-Meier method, and were compared by the log-rank test. Univariate and multivariate Cox regression were utilized to analyze the effect of sarcopenia on the prognosis of HCC after laparoscopic radical surgery. Results:The 1- and 3-year cumulative survival rates of control group were 96.4% and 81.2%, which were higher than those of the sarcopenia group (83.2% and 48.9%, respectively, χ2=19.67, P<0.001). The 1- and 3-year recurrence-free survival (RFS) rates of control group were 88.4% and 66.1%, which were higher than those of sarcopenia group (70.9% and 37.7%, respectively, χ2=18.80, P<0.001). Multivariate Cox regression analysis showed that the risk of recurrence ( HR=1.35, 95% CI: 1.20-1.59, P<0.001) and the risk of death ( HR=2.21, 95% CI: 1.23-3.41, P=0.001) after laparoscopic radical resection for HCC in patients with sarcopenia rises compared to non-sarcopenic patients. Conclusion:Sarcopenia is a risk factor for the survival and recurrence of HCC after laparoscopic radical surgery.

Objective:To establish a machine learning model to predict the risk of post hepatectomy liver dysfunction (PHLD) in patients with hilar cholangiocarcinoma (HCCA).Methods:Clinical data of 203 patients with HCCA undergoing open radical hemihepatectomy in Henan University People's Hospital from January 2017 to December 2023 were retrospectively analyzed, including 112 males and 91 females, aged 63 (55, 69) years. According to the diagnostic criteria for PHLD, patients were divided into two groups: PHLD group ( n=45) and non-PHLD group ( n=158). Clinical data such as age, sex, neutrophil count (NEU), systemic immunoinflammatory index (SII), nutritional prognosis index (PNI), neutrophil to lymphocyte ratio (NLR), operative time and complications were compared between the two groups. The variables with statistically significant difference between the two groups were included in seven machine learning models, namely logistic regression, random forest, extreme gradient boosting, light gradient boosting, decision tree, gaussian naive bayes and support vector machine. The area under receiver operating characteristic curve optimization model was adopted, and Shapliga sum-interpretation method (SHAP) was used to analyze and interpret the final optimal model. Results:There were statistically significant differences in age, preoperative data including management of jaundice, albumin, total bilirubin, aspartate aminotransferase, NEU, SII, PNI, and NLR, operative time, postoperative complication of Dindo-Clavien≥Grade Ⅲ, and the ratio of FLR/TLV between in the two groups (all P<0.05). Finally, it was determined that the prediction performance of the extreme gradient boosting model was the best, with an area under curve of 0.888 (95% CI: 0.776-0.985), an accuracy of 0.854, a sensitivity of 0.506, a specificity of 0.965, an F1 value of 0.625, and a Kappa value of 0.519. SHAP analysis of the extreme gradient boosting model showed that total bilirubin on admission, operation time, postoperative complication of Dindo-Clavien≥grade Ⅲ, SII and NEU were five important factors of this model, which were positively correlated with the occurrence of PHLD in HCCA patients. Conclusion:The extreme gradient boosting model established in this study has a good predictive performance and stability for PHLD in HCCA patients.