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.

Objective:To investigate the possible role of miR-181d in regulating the multidrug resistance (MDR) of small cell lung cancer (SCLC) and its clinical significance. Methods: Quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and Western blot were used to investigate the differential expression of miR-181d and BCL2 from mRNA and protein levels in the chemo-sensitivity cell H69 and the chemo-resistance cell H69AR. The miR-181d expression in H69AR was then upregulated. More-over, CCK8 assay was employed to detect the sensitivities of the cells to chemotherapy drugs, such as ADM, DDP, and VP-16. Mean-while, the expression of miR-181d in the specimens of 87 cases with SCLC were detected using QRT-PCR. All patients received the chemotherapeutic regimen of EP (etoposide+cisplatin). Correlation of the miR-181d expression with clinicopathological features, prog-nosis, and survival time of the patients was studied. Results:miR-181d was downregulated in the SCLC multidrug-resistant cell line H69AR and chemo-resistant patients. Moreover, miR-181d was concurrent with the upregulation of BCL2 protein compared with the parental H69 cell line and chemo-sensitive patients (P<0.001). miR-181d expression in H69 cells resistant to chemotherapy drugs (ADM, DDP, and VP-16) was inhibited (P<0.01). Enforced miR-181d expression reduced the BCL2 protein level and sensitized H69AR cells to chemotherapy drugs (P<0.01). miR-181d expression was associated with tumor stage, sensitivity of chemotherapy, and survival time (all P<0.001). Patients with high miR-181d expression had longer overall survival and progress-free survival time com-pared with those with low miR-181d expression (P<0.001). Conclusion: miR-181d may play a role in the development of MDR in SCLC and may be a potential predictive factor for treatment efficacy.

OBJECTIVETo explore the expression of cancerous inhibitor of phosphatase 2A (CIP2A) protein in small cell lung cancer and their relationship with clinicpathological features and prognosis.

METHODSA total of 112 cases of surgical specimens or bronchoscopic biopsies of small cell lung cancer were collected. There were specimens of 94 cases of SCLC tissues and 40 cases of paracancerous lung tissues. Quantitative RT-PCR and immunohistochemistry analysis were performed to determine the CIP2A expression in SCLC tissues. Kaplan-Meier curves were used to estimate the association between CIP2A expression and clinicopathological characteristics and prognosis of the patients.

RESULTSThe expression of CIP2A in SCLC tissue was 7.605 ± 1.893, significantly higher than that in the paracancerous tissues (1.041 ± 0.786) (P < 0.01). The positive rate of CIP2A expression in cancer tissues was 82.8%, significantly higher than that in the paracancerous tissues (13.3%) (P < 0.01). The median disease-free survival was 9.88 months in the CIP2A-high expressing patients, significantly shorter than the 20.92 months in CIP2A-low expressing patients (P < 0.001). CIP2A expression was significantly correlated with the tumor stage, chemotherapeutic sensitivity, and survival (P < 0.05 for all).

CONCLUSIONSCIP2A expression is associated with the pathogenesis of SCLC, and may become a potential prognostic indicator of SCLC.

Autoantigens ; metabolism ; Biomarkers, Tumor ; metabolism ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung ; metabolism ; Lung Neoplasms ; metabolism ; mortality ; Membrane Proteins ; metabolism ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Small Cell Lung Carcinoma ; metabolism ; mortality

OBJECTIVETo investigate the role of RLIP76 in regulating multi-drug resistance in small cell lung cancer (SCLC), and to analyze the relationship between its expression and prognosis.

METHODSThe expressions of RLIP76 protein and gene were detected by Western blotting and real-time PCR (RT-PCR) in both the chemosensitive SCLC H69 cell line and chemoresistant H69AR cell line, respectively. siRNA was transfected into the H69AR cells to inhibit RLIP76 expression, and eGFP-RLIP76 was transfected into the H69 cells to enhance RLIP76 expression. The drug-sensitivity of cells to chemotherapeutic drugs (ADM, DDP, VP-16) were detected by CCK8 assay. The expression of RLIP76 in the SCLC tissues was detected by immunohistochemistry. The relationship of RLIP76 expression with clinicopathological features and prognosis of the patients was analyzed.

RESULTSThe expression of RLIP76 in H69AR cells was 13.675 ± 0.983, significantly higher than 1.074 ± 0.107 in the H69 cells (P < 0.01). The drug-sensitivities of H69AR cells to chemotherapeutic drugs were significantly increased when the expression of RLIP76 was down-regulated (P< 0.001). The sensitivities of H69 cells to chemotherapeutic drugs ADM, DDP and VP-16 were significantly decreased after transfection with eGFP-RLIP76 up-regulating the RLIP76 expression (P = 0.003). The positive expression rates were 61.3% and 9.4% in the SCLC tumor tissues and para-cancerous tissues, respectively (P < 0.01). The expression of RLIP76 was significantly correlated with clinical stage, chemosensitivity and overall survival of the SCLC patients (P < 0.05).

CONCLUSIONSOur results suggest that RLIP76 is involved in the regulation of small cell lung cancer multidrug resistance. RLIP76 may serve as a potential target gene to evaluate the chemosensitivity and clinical prognostic for small cell lung cancer.

ATP-Binding Cassette Transporters ; metabolism ; physiology ; Antineoplastic Agents ; pharmacology ; Cisplatin ; pharmacology ; Down-Regulation ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Etoposide ; pharmacology ; GTPase-Activating Proteins ; metabolism ; physiology ; Humans ; Lung Neoplasms ; drug therapy ; metabolism ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Small Cell Lung Carcinoma ; drug therapy ; metabolism ; Transfection ; Up-Regulation