ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Background and Aims:The incidence of intrahepatic cholangiocarcinoma(ICC)has been increasing in recent years.Due to its insidious onset and low rate of early diagnosis,radical resection remains the only potential curative treatment.Lymph node metastasis is a major adverse prognostic factor in ICC,but the scope and therapeutic value of lymphadenectomy remain controversial.Previous studies suggest that patients with central ICC may derive greater survival benefit from lymphadenectomy than those with peripheral ICC.Preoperative assessment of lymph node status mainly relies on imaging,but its accuracy is limited.This study aimed to investigate the prognostic impact of lymphadenectomy in ICC patients at different anatomical sites to inform surgical decision-making.Methods:A retrospective analysis was conducted on 220 ICC patients who underwent radical resection at the 904th Hospital of the Joint Logistic Support Force of the PLA from May 2016 to May 2021.The cohort included 126 males and 94 females,with a mean age of(56.76±13.15)years.Patients were categorized into peripheral ICC(n=144)and central ICC(n=76)groups.Clinical characteristics,albumin-bilirubin(ALBI)grade,preoperative risk of lymph node metastasis,number of lymph nodes dissected,lymph node metastasis status,and postoperative survival outcomes were compared.Subgroup analyses were conducted to assess the prognostic value of the number of lymph nodes dissected under different risk stratifications.Results:Significant differences were observed between peripheral and central ICC in ALBI grade(x2=9.952,P=0.002),preoperative lymph node metastasis risk(x2=6.166,P=0.014),number of lymph nodes dissected(x2=4.167,P=0.042),and lymph node metastasis rate(x2=7.331,P=0.007).The 3-year overall survival(OS)rate was higher in peripheral ICC(31.94％)than in central ICC(15.79％)(x2=13.890,P＜0.001).Among central ICC patients,those with ≥6 lymph nodes dissected had better 3-year OS than those with＜6(16.89％vs.13.04％,x2=3.894,P=0.048).In the high-risk subgroup of central ICC,≥6 lymph nodes dissected was also associated with improved 3-year OS compared with＜6(15.62％vs.11.11％,x2=3.962,P=0.047).In contrast,the number of lymph node dissections had no significant prognostic impact in peripheral ICC or in patients classified as low risk.Conclusion:Patients with peripheral ICC had a better prognosis than those with central ICC.Adequate lymphadenectomy(≥6 nodes)improved survival and enhanced staging accuracy in central ICC patients at high risk of lymph node metastasis,highlighting the importance of preoperative risk assessment for optimizing surgical strategies.

Background and Aims:The incidence of intrahepatic cholangiocarcinoma(ICC)has been increasing in recent years.Due to its insidious onset and low rate of early diagnosis,radical resection remains the only potential curative treatment.Lymph node metastasis is a major adverse prognostic factor in ICC,but the scope and therapeutic value of lymphadenectomy remain controversial.Previous studies suggest that patients with central ICC may derive greater survival benefit from lymphadenectomy than those with peripheral ICC.Preoperative assessment of lymph node status mainly relies on imaging,but its accuracy is limited.This study aimed to investigate the prognostic impact of lymphadenectomy in ICC patients at different anatomical sites to inform surgical decision-making.Methods:A retrospective analysis was conducted on 220 ICC patients who underwent radical resection at the 904th Hospital of the Joint Logistic Support Force of the PLA from May 2016 to May 2021.The cohort included 126 males and 94 females,with a mean age of(56.76±13.15)years.Patients were categorized into peripheral ICC(n=144)and central ICC(n=76)groups.Clinical characteristics,albumin-bilirubin(ALBI)grade,preoperative risk of lymph node metastasis,number of lymph nodes dissected,lymph node metastasis status,and postoperative survival outcomes were compared.Subgroup analyses were conducted to assess the prognostic value of the number of lymph nodes dissected under different risk stratifications.Results:Significant differences were observed between peripheral and central ICC in ALBI grade(x2=9.952,P=0.002),preoperative lymph node metastasis risk(x2=6.166,P=0.014),number of lymph nodes dissected(x2=4.167,P=0.042),and lymph node metastasis rate(x2=7.331,P=0.007).The 3-year overall survival(OS)rate was higher in peripheral ICC(31.94％)than in central ICC(15.79％)(x2=13.890,P＜0.001).Among central ICC patients,those with ≥6 lymph nodes dissected had better 3-year OS than those with＜6(16.89％vs.13.04％,x2=3.894,P=0.048).In the high-risk subgroup of central ICC,≥6 lymph nodes dissected was also associated with improved 3-year OS compared with＜6(15.62％vs.11.11％,x2=3.962,P=0.047).In contrast,the number of lymph node dissections had no significant prognostic impact in peripheral ICC or in patients classified as low risk.Conclusion:Patients with peripheral ICC had a better prognosis than those with central ICC.Adequate lymphadenectomy(≥6 nodes)improved survival and enhanced staging accuracy in central ICC patients at high risk of lymph node metastasis,highlighting the importance of preoperative risk assessment for optimizing surgical strategies.

Colorectal cancer is currently one of the most common malignant tumors in the world,and its incidence and mortality rates have gradually increased in recent years.As insidious symptoms characterize early colorectal cancer,most of the patients have already developed into late or advanced stages in the primary survey.For stage Ⅳ metastatic colorectal cancer(mCRC),surgery supplemented with chemotherapy or radiotherapy for mCRC patients has a low 5-year survival rate.With the development of immunology in recent years,PD-1/PD-L1 inhibitors have made breakthroughs in treating malignant tumors.They also have improved the therapeutic efficacy of some mCRC patients,especially those with microsatellite instability-high/mismatch repair deficient.The guidelines recommend this approach.However,patients with microsatellite stable/mismatch repair proficiency,which accounts for more than 90%,are poorly treated with PD-1/PD-L1 inhibitors.Fortunately,there are several clinical studies that reported that some of this type of mCRC can gain some benefit.In this review,we examined the anti-tumor mechanism of PD-1/PD-L1 inhibitors and the latest progress of PD-1/PD-L1 inhibitor's clinical application in patients of mCRC with different genotypes.We discussed the prospect of PD-1/PD-L1 inhibitor combination therapy to provide a reference to the benefit of this type of patients and provide information for optimizing the dosing regimen of PD-1/PD-L1 inhibitors in the treatment of mCRC.

The seventh article of Measures for the Ethical Review of Biomedical Research Involving Humans (2016) stipulated that medical and health institutions without an ethics committee shall not carry out biomedical research involving Humans. The Opinions on Strengthening the Governance of Ethics in Science and Technology, issued in March 2022, clearly stated that the institutions that do not meet the conditions for establishing a scientific and technological ethics (review) committee should entrust other institutions to conduct the review. The fourteenth article of Measures for Ethical Review of Life Science and Medical Research Involving Humans (2023) proposes that if an institution, which carries out life science and medical research involving humans, has not established an ethics committee or its ethics committee is not competent for ethics review, it can entrust a competent ethics committee or regional ethics committee in writing to carry out ethical review. Most medical institutions at or above the second level in China have set up ethics committees. While most universities and colleges, scientific research institutions, enterprises and grass-roots medical and health institutions have not set up ethics committees, which lack a working system to protect the safety and interests of the participants, and is difficult to conduct life sciences and medical research involving humans. At present, there is a need for some research institutions that do not have the conditions to establish ethics committees to entrust their projects of life science and medical research involving humans to other institutions for ethical review. The entrusted review is still in the exploratory stage, and there is no relevant specification. The hasty implementation of entrusted review may not achieve the goal of effectively protecting the safety and interests of the participants, and even cause legal disputes. Based on the thematic discussion, with reference to the relevant laws and regulations, departmental rules, ethical standards, and the experience of the ethics committees of some domestic institutions in implementing the entrusted review, the guideline was formulated for the reference of the current entrusted review to ensure the safety and interests of the participants.

Perimenopausal syndrome is a common uncomfortable symptom in women during the perimenopausal period, with a high incidence, a long duration, and adverse effects on physical and psychological, patients bear a heavy burden of symptoms, and increase the risk of adverse events in the elderly stage, increase the social medical burden. With the development of sports rehabilitation research, more and more attention has been paid to the effect of exercise on human health. This paper reviews the studies on exercise rehabilitation in women with perimenopausal syndrome, including exercise forms, exercise intensity, exercise time and exercise effect, in order to provide basis for the relevant research and practice.

Objective To investigate the technical and therapeutic effects of laparoscopic surgery for adult patients with Dong Type C bile duct dilatation.Methods A retrospective cohort study approach was used.The clinical data of 47 patients with Dong Type C adult biliary dilatation who underwent surgery in Fujian Provincial Hospital from January 2014 to December 2017 were collected.There were 12 males and 35 females.The age ranged from 16 to 68 years,with a median age of 30 years.According to different surgical methods,the patients were divided into the laparoscopic group (treated with laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy,n =21) and the open group (treated with traditional open operation,n =26).The intraoperative blood loss,complication rate,operation time,postoperative intestinal function recovery time and postoperative hospital stay were observed.Measurement data with normal distribution were expressed as mean ± standard deviation (Mean ±SD) and analyzed by t test.Comparison of count data was done by the chi-square test.Results There was no perioperative deaths in either group.There was no significant difference in intraoperative blood loss and complication rate between the two groups (P ＞ 0.05).The operation time of the laparoscopic group was significantly longer than that of the open group[(333.7 ±61.1) min vs (235.9 ±64.3) min],with statistically significant difference between graps (P =0.000).The recovery time for the intestinal function of the laparoscopic group was significantly shorter than that of the open group [(2.2 ± 0.5) d vs (2.9 ± 0.6) d],with statistically significant difference between groups (P =0.000).The postoperative hospital stay in the laparoscopic group was significantly shorter than the open group [(7.1 ± 1.8) d vs (12.0 ± 5.9) d],with statistically significant difference between groups (P =0.001).Conclusion For adult biliary dilatation patiens with Dong Type C,laparoscopic surgery is safe and feasible with the advantages of mini-invasive and quick recovery.

Objective:To investigate the inhibitory effect of perillyl alcohol (PA) on the proliferation and invasion of tung cancer cell A549,and the influence of PA on tumor angiogenesis was studied.Methods:Different concentrations of PA and erlotinib were added into lung cancer cell A549,the inhibiting effect of drug group on lung cancer cell A549 was found by MTT assay.The inhibiting effect of PA on lung cancer cell A549 invasion was measured by Transwell assay.ROS changes of PA on lung cancer cell A549 was detected by fluorescent.Influence of PA on Caspase-3 activity of lung cancer cell A549 was measured by spectrophotometry,VEGF,HIF-1 α,COX-2 expression in lung cancer cell A549 was measured by Western blot,and the NF-κB activity of lung cancer cell A549 was measured by EMSA.Results:Compared with blank control group,cell growth inhibition rate of PA and erlotinib on lung cancer cell A549 was increasing with the increased concentrations (10,50,100 μ,g/ml),the difference was statistically significant (P＜ 0.05),the invasion ability of lung cancer cell A549 was decreased continuously,the difference was statistically significant (P＜0.05).The ROS level of lung cancer cell A549 had no obvious change with the increasing density of erlotinib,but obviously increased with the increasing concentrations of PA (10,50,100 μg/ml).With the increasing concentrations of PA,the expression of COX-2,VEGF and HIF-1α were continuously decreased.EMSA assay showed that NF-κB was continuously decreased with the increasing concentrations of PA.Conclusion:The antitumor mechanism of PA on lung cancer cell A549 might be related to increase the expression level of ROS and reduce the expression of activity of NF-κB,COX-2,VEGF and HIF-1α with angiogenesis signaling pathway.

Objective To investigate the expression and clinical significance of long non-coding RNA (lncRNA) RP11-629B11.4 in triple negative breast cancer (TNBC) patients.Methods The expression of lncRNA RP11-629B11.4 was detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) in TNBC tissues (n =45) and non triple negative breast cancer (N-TNBC,n =89) to analyze the relationship between the expression of lncRNA RP11-629B11.4 and the prognosis of patients.Results The expression of lncRNA RP1 1-629B11.4 in TNBC tissues was 7.805 ± 0.538,significantly higher than that in N-TNBC tissues (1.637 ± 0.409,t =21.460,P ＜ 0.001).The expression of lncRNA RP11-629B11.4 in the TNBC patients was related with histological grade (x2 =7.540,P =0.040),clinical stage (x2 =9.858,P =0.007),lymph node metastasis (x2 =4.388,P =0.036) and Ki-67 expression (x2 =7.872,P =0.005).In the N-TNBC group,there was no significant correlation between the expression of lncRNA RP11-629B11.4 and clinicopathological characteristics (all P ＞ 0.050).The progression free survival time of TNBC patients with higher expression of lncRNA RP11-629B11.4 was (15.90 ±2.76) months,shorter than that of patients with lower expression (26.62 ± 3.80) months,with a statistically significant difference (x2 =49.750,P ＜ 0.001).The overall survival time of TNBC patients with lower expression of lncRNA RP11-629B11.4 was (38.84 ±3.55) months,significantly longer than that of patients with higher expression [(24.69 ± 3.50) months],with a statistically significant difference (x2 =50.730,P ＜ 0.001).Cox regression model analysis showed that lymph node metastasis (HR =1.980,P =0.019),the expression of lncRNA RP11-629 B11.4 (HR =4.030,P ＜ 0.001) clinical stage (HR =2.670,P =0.008) and were independent prognostic factors in patients with TNBC.Conclusion The lncRNA RP11-629B11.4 is over-expressed in TNBC.lncRNA RP11-629B11.4 may be involved in the regulation of TNBC,and it may be used as a potential target for evaluating the prognosis of TNBC.

Objective:To investigate the exression of miR-34a on lung cancer and normal lung tissues,and the effect and mechanism of miR-34a in lung cancer cell invasion and migration.Methods: qPCR was used to detect the expression of miR-34a on lung cancer.miR-34a-mimic and miR-34a-inhibitor were used to overexpress and knockdown miR-34a.qPCR was used to detect the effectiveness.Western blot was used to detect the expression of Snail after induced with miR-34a-mimic and miR-34a-inhibitor.Luciferase reporter gene was used to detect interaction between miR-34a and Snail.Transwell invasion assay was used to detect invasion ability after induced with miR-34a-mimic and miR-34a-inhibitor.Scratch assay was used to detect migration ability after induced with miR-34a-mimic and miR-34a-inhibitor.The expression of E-cadherin,Vimentin and Twist were detected by Western blot.Results: miR-34a expression was significantly reduced in lung cancer.With the stage of lung cancer progression,the expression of miR-34a reduced.With the differentiation of lung cancer progression,the expression of miR-34a decreased.Decreasing of miR-34a was associated with lung cancer lymph node metastasis.miR-34a-mimic and miR-34a-inhibitor could overexpress and knockdown miR-34a.miR-34a could regulate expression of Snail.Snail was the direct target of miR-34a;miR-34a could regulate the invasion ability of human lung carcinoma H1650 cells;miR-34a could regulate the migration of human lung carcinoma H1650 cells;miR-34a could regulate the expression of E-cadherin,Vimentin and Twist.Conclusion: miR-34a plays the role of tumor suppressor factor in lung cancer.miR-34a can regulate the invasion and migration ability of lung carcinoma H1650 cells by Snail induced EMT.