Objective The aim of this study was to investigate the mechanism of placental growth factor(PLGF)mediated crosstalk between non-small cell lung cancer(NSCLC)cells and tumor-associated macrophages(TAM). Methods A NSCLC model in mice was established by tail vein injecting NSCLC A549 cells into 10-weeks-old male NOD/SCID mice,which were transfected by adeno-associated virus(AAV).A flow cytometry was used to detect various macrophage(MΦ)subtypes.Levels of PLGF,vascular endothelial growth factor receptor-1(Flt-1) and transforming growth factor β1(TGF-β1)were examined in tumor cells and TAM by RT-qPCR.With the different cultured media of A549 cells and MΦ cells,it could divide into A549 group and MΦ group,A549+MΦ group,A549+MΦ+ sFlt-1 group(with 10 μg/L sFlt-1),PLGF+MΦ group(with 100 ng PLGF)and PLGF+MΦ+ sFlt-1 group(with 100 ng PLGF and 10 μg/L sFlt-1).Transwell assay and MTT assay were used to detect the proliferation and migration of A549 cells with different co-culture conditioned media.With the different cultured media of HUVEC cell,it could divide into control group,conditioned media(CM)group,CM+SB431542 group,TGF-β1 group and TGF-β1+SB431542 group.HUVEC cells collagen gel assay was used to detect the tumor vascularization. Results Compared with RFP- cells,PLGF was predominantly expressed by tumor cells(31.72±4.69 vs. 2.31±0.06,P＜0.001),while Flt-1 was predominantly expressed by CD163+macrophages(P＜0.001).The proliferation ability of A549 cells in the A549+MΦ group was significantly higher than in A549 group and A549+MΦ+sFlt-1 group(OD value:3.62±0.23 vs. 4.53±0.34 vs. 3.71±0.37,P＜0.05).TGF-β1 in TAM/M2 macrophages was higher than that in M1 macrophages(0.99±0.23 vs. 0.07±0.02,P＜0.05).The formation of tubular structures in HUVEC cells were the most in the CM group and TGF-β1 group(P＜0.05),which was inhibited by TGF-β1 inhibitor SB431542. Conclusion The crosstalk between TAM and NSCLC cells via PLGF/Flt-1 and TGF-β1 signal pathways promotes the growth and vascularization of NSCLC.

Objective The objective of this study was to investigate the effects of human dental pulp stem cell derived exosomes (hDPSCs-exo) on the proliferation and migration of oral squamous carcinoma CAL-27 cells. Methods hDPSCs-exo was extracted by ultracentrifugation.CAL-27 cells were treated with different concentrations of hDPSCs-exo.The proliferation and migration of CAL-27 cells were detected by MTT assay,Transwell and scratch assays;Western Blot was used to detect the levels of PI3K/AKT signaling pathway related proteins. Results The results of MTT assay showed that only 80 μg/mL of hDPSCs-exo had an inhibitory effect on the proliferation of CAL-27 cells on the 5th day (P＜0.05),and the other concentration groups had no significant effect.The results of Transwell and scratch assays showed that 20,60,and 80 μg/mL of hDPSCs-exo could significantly promote migration of CAL-27 cells (P＜0.05).The results of Western blot showed that the levels of PI3K/AKT signaling pathway related proteins PI3K and P-AKT were significantly up-regulated in CAL-27 cells after hDPSCs-exo treatment(P＜0.05). Conclusion High concentration of hDPSCs-exo can inhibit the proliferation of CAL-27 cells,and the appropriate concentration can significantly promote the migration of CAL-27 cells.Its mechanism of action may be related to the activation of the PI3K/AKT signaling pathway.

Objective The aim of this study was to investigate the effect of lncRNA XIST on the proliferation and invasion of T-acute lymphocytic leukemia(T-ALL)cells through the regulation of miR-375-Notch1 axis. Methods Fifty-seven patients with T-ALL who were treated from June 2018 to March 2021 were collected as the observation object(T-ALL group),and 55 healthy people who underwent physical examination during the same period were selected as the control group.The levels of lncRNA XIST in the two groups of patients and CCRF-CEM cell lines were detected by qRT-PCR;CCRF-CEM cells were transfected with si-lncRNA XIST to silence lncRNA XIST,and miR-375 mimics were transfected to overexpress miR-375.CCK-8 method,transwell invasion test and flow cytometry were used to detect the proliferation,invasion and apoptosis of CCRF-CEM cells;the luciferase reporter gene method was used to detect lncRNA XIST target gene;Western blot was used to detect the expressions of Notch1,ADAM-17 and Hes1 protein. Results Compared with the control group,the expression of lncRNA XIST and Notch1 mRNA in the T-ALL group was significantly increased(P＜0.05),while the level of miR-375 was significantly decreased(P＜0.05),and the level of Notch1 protein in T-ALL patients was significantly higher than that in the control group(P＜0.001).After transfection with si-lncRNA XIST to silence lncRNA XIST,the proliferation and invasion of CCRF-CEM cells were significantly decreased(P＜0.05),and the apoptosis was significantly increased(P＜0.05).The luciferase reporter gene revealed that miR-375 was the target of lncRNA XIST.After CCRF-CEM cells were transfected with miR-375,the number of cell proliferation and invasion were significantly decreased(P＜0.05),and the apoptosis was significantly increased(P＜0.05).Transfection of si-lncRNA XIST could significantly up-regulate the level of miR-375,down-regulate the level of Notch1 mRNA,and down regulate the expression of Notch1,ADAM-17 and Hes1 protein(P＜0.05). Conclusion lncRNA XIST is highly expressed in T-ALL patients,which may affect the biological function of leukemia cells through the miR-375-Notch1 axis.

Objective The aim of this study was to analyze the clinical data of nasopharyngeal carcinoma cases in Nantong Tumor Hospital from 2002 to 2017,to understand the distribution and epidemic characteristics of nasopharyngeal carcinoma in Nantong,and to provide reference information for early diagnosis and screening of nasopharyngeal carcinoma and the formulation of comprehensive prevention and treatment measures. Methods The case data of 319 nasopharynx cancer patients were collected in the tumor registration database of Nantong Tumor Hospital from January 2002 to December 2017,and the distribution of age,sex,symptoms,course of disease,number of hospitalizations and pathological types etc.of nasopharyngeal carcinoma were statistically analyzed. Results Among 319 nasopharynx cancer patients,221 were male(69.28%)and 98 female(30.72%).The minimum age was 16 years old,the maximum age was 83 years old,and the median age was 55 years old.The patients were mainly 40-69 years old.The median duration of hospitalization was 5.02 months,and those over 6 months accounted for 50.47%.Among the clinical symptoms,43.57% were nasal symptoms,and 40.44% were accompanied by neck tumors.In TNM staging,124 cases(38.87%)were T1-T2,103 cases(32.29%)were T3-T4,33 cases(10.34%)were N0,176 cases(N1-N2)(55.17%),and 48 cases(15.05%)were distal recurrence and metastasis(M1).The clinical staging was mainly in the middle and late stages:Phase Ⅲ was the most common(115 cases,36.05%),followed by phase IV(78 cases,37.62%).The most common type of pathological tissue was non-keratinizing undifferentiated carcinoma(98.43%).Distribution of hospitalizations times:20.06% were hospitalized once,53.61% were hospitalized 2-5 times,and the average of hospitalization time was(4.48±3.71).The 5-year observed survival rates of early cases and middle and late cases were 77.50% and 72.96%,respectively,with statistical significance(P＜0.05). Conclusion The majority of hospitalized nasopharynx cancer patients are males,middle-aged and elderly,and the majority of non-keratinized undifferentiated cancer patients are middle and late stage patients.Early diagnosis and treatment of nasopharynx cancer should be attention.

Objective The aim of this study was to investigate the clinical application value of the integrated wrapping and reinforcing technique of liver round and falciform ligament in pancreaticoduodenectomy(PD). Methods The clinical data of 759 patients who underwent PD or pylorus-preserving pancreaticoduodenectomy(PPPD)from January 2016 to December 2021 were retrospectively analyzed.According to whether the integrated wrapping and reinforcing technique of the liver round and falciform ligament was used or not,the patients were divided into the wrapping and reinforcing group(372 cases)and the non-wrapping or reinforcing group(387 cases).The basic characteristics,intraoperative data,postoperative data,and late post-pancreatectomy hemorrhage(PPH)data were compared between the two groups. Results The incidences of clinically relevant postoperative pancreatic fistula(CR-POPF),grade C pancreatic fistula,grade B/C and grade C PPH,late PPH,extraluminal PPH,intra-abdominal infection and percutaneous catheter drainage,90-day re-operation,and PPH-related 90-day re-operation were significantly lower in the wrapping and reinforcing group than those in the non-wrapping or reinforcing group(P＜0.05).And the postoperative hospital stay was also significantly shortened in the wrapping and reinforcing group(P＜0.05).The incidences of late extraluminal PPH,grade B/C and grade C late extraluminal PPH,invasive treatment and re-operation were significantly lower in the wrapping and reinforcing group than those in the non-wrapping or reinforcing group(P＜0.05). Conclusion The integrated wrapping and reinforcing technique of the liver round and falciform ligament can reduce the incidence of CR-POPF and late PPH after PD,especially the incidence of grade C pancreatic fistula,grade B/C and grade C late extraluminal PPH.At the same time,it can reduce the rate of intra-abdominal infection,percutaneous catheter drainage and re-operation,and shorten the postoperative hospital stay.

Objective The objective of this study was to investigate the application value of multimodal MRI in evaluating parauterine invasion of stage IB1-IIA2 cervical cancer. Methods The multimodal MRI examination and postoperative pathological data of 106 patients with cervical cancer who underwent radical hysterectomy in Shaanxi Provincial People's hospital from August 2015 and April 2021 were collected.Two groups of MRI status were performed by two experienced physicians to evaluate the parauterine infiltration of the imaging data. Results Parauterine invasion was found in 28 of 106 patients(26.4%).In the plain MRI group,the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of physician 1 in diagnosing parauterine invasion were 71.4%,84.6%,62.5%,89.2% and 81.1%,respectively.The corresponding rates of physician 2 were 67.9%,79.5%,54.3%,87.3% and 76.4%,respectively;the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of physician 1 in the diagnosis of parauterine invasion in the multimodal MRI group were 85.7%,98.7%,96.0%,95.1% and 95.3%,and the corresponding results for physician 2 were 89.3%,97.4%,92.6%,96.2% and 95.3%,respectively.The judgment of parauterine invasion by two physicians using multimodal MRI was better than that of single plain scan,and the specificity,positive predictive value and diagnostic accuracy were statistically different(P＜0.05).There was a high degree of agreement(κ=0.790)in the examination to assess the consistency of parauterine invasion,which was better than moderate agreement(κ=0.410)for plain scans. Conclusion Compared with conventional plain MRI,multimodal MRI can significantly improve the diagnostic accuracy of parauterine invasion in stage IB1-IIA2 cervical cancer,and can be used as a routine and effective method for judging parauterine invasion of cervical cancer.

As a potential treatment strategy for malignant tumors,ferroptosis has attracted widespread attention.Ferroptosis is an iron-dependent regulatory cell death that is typically characterized by the accumulation of intracellular reactive oxygen species and lipid peroxidation.With the rapid development of nanotechnology and biomaterial technology,multifunctional nanoformulation-mediated ferroptosis combined therapy shows great clinical application prospects in tumor diagnosis and treatment.This article reviews the mechanism of nano-formulation-induced ferroptosis and the latest research progress of ferroptosis-based combined antitumor therapy,and summarizes the application prospects and challenges of ferroptosis in clinical tumor treatment,expecting new ideas for tumor strategies to develop new and efficient anti-cancer drugs.

Liver cancer is a common malignant tumor in the world.Most patients with liver cancer were in the middle and late stages when diagnosed.Early growth response factor 1(Egr1)is a transcription factor that is induced during liver injury and regulates the expression of genes involved in cell proliferation,involved in cell proliferation and the role of Egr1 in liver injury and repair,and the lack of Egr1 will delay the process of liver regeneration.Recent studies have emphasized the dual role of Egr1 in the occurrence,development and treatment of liver cancer,thus affecting the progress of liver cancer.This article reviews the possible role of Egr1 in the occurrence,development and treatment of liver cancer,and analyzes in details the complex signal pathways involved by Egr1,so as to provide reference for clinical efficacy prediction and discovery of new therapeutic targets.

Bacterial biofilm is a microbial population formed by bacteria and extracellular polymers,which has the ability to enhance antibiotic resistance and anti-host immunity.Bacterial biofilms in the tumor microenvironment can induce inflammation-cancer transformation,promote cancer cell proliferation and metastasis,and enhance tumor drug-resistance,which affect the biological process of tumors.In addition,bacterial biofilms have also been shown to synergize with anticancer drugs to inhibit cancer cell proliferation,promote targeted colonization of anticancer drugs,and enhance host immune function.This paper reviews the research on bacterial biofilms in influencing the occurrence,development and anti-tumor treatment of malignant tumors.

Trastuzumab is effective in the treatment of human epidermal growth factor receptor 2(HER2)positive breast cancer,but the high drug resistance rate limits its clinical application.This article reviews and summarizes the mechanism of trastuzumab resistance in HER2-positive breast cancer,and analyzes the treatment strategies for HER2-positive breast cancer after drug resistance,in order to provide reference for further research and clinical treatment plan formulation.

Inhibition of apoptosis is a prominent feature of hematological malignancies.B-cell lymphoma-2(BCL-2)is a key protein regulator of apoptosis and is expressed to varying degrees in a variety of hematological malignancies.The anti-apoptotic ability of tumor cells with high expression of BCL-2 is significantly enhanced,and targeted inhibition of BCL-2 has become one of the research hotspots in anti-hematological tumors.Venetoclax(VEN)is the first BCL-2 inhibitor(BCL-2i)approved for the treatment of chronic lymphocytic leukemia,acute myeloid leukemia and myelodysplastic syndromes.Studies have shown that VEN also has antitumor activity against other hematological malignancies such as B-cell non-Hodgkin lymphomas and multiple myeloma.This article briefly reviews the anti-apoptosis mechanism of BCL-2,the clinical application of BCL-2i in hematological malignancies,and the possible mechanism of BCL-2i resistance.

Pancreatic cancer is a malignant tumor of digestive system with hidden onset and poor prognosis,which is characterized by difficult early diagnosis and short survival time in the advanced stage.The tumor microenvironment(TME)of pancreatic cancer is often accompanied by the infiltration of a large number of immune cells.As an important part of the TEM,tumor-associated neutrophils(TANs)play an important role in the process of tumor.Relevant studies have shown that TANs play multiple roles in the TME of pancreatic cancer.This article reviews the relationship between TANs and pancreatic cancer to provide ideas for understanding the pathogenesis of pancreatic cancer and proposing new therapies.

Non-small cell lung cancer(NSCLC)is the most common histological type of lung cancer,which is mostly diagnosed at advanced stage and has a high mortality.The application of immune checkpoint inhibitors(ICIs)has significantly improved the 5-year survival rate of patients with advanced NSCLC,but while bringing survival benefits,it also leads to adverse events that are different from traditional treatment regimens,namely immune-related adverse events(irAEs).In recent years,the correlation between irAEs and clinical efficacy of ICIs has become a research hotspot.This article reviews the research progress on the correlation between irAEs and the efficacy of immunotherapy in advanced NSCLC.

Cancer is the main cause of death in China,and its pathogenesis is complex and has not been fully elucidated.Surgery is the main treatment of cancer,and the abnormal neuropsychiatric symptoms during the perioperative period of cancer patients often affect their prognosis.In recent years,numerous studies have found that gut microbiota play an important role in the occurrence and development of perioperative neuropsychiatric symptoms in cancer patients.This article aims to describe the research status of the relationship between intestinal flora and neuropsychiatric symptoms in cancer patients during perioperative period,in order to provide a new breakthrough for cancer prevention and treatment from the perspective of intestinal flora.

Breast cancer is highly heterogeneous,and its heterogeneity is the main reason for high misdiagnosis rate,poor treatment response and poor prognosis.Texture analysis evaluates the heterogeneity of tumor body and its surrounding stroma by extracting texture features of different sequence images,and combines the results with clinical,histopathological,and genomic information,so that it can make a noninvasive prospective evaluation and prediction of breast lesions.With the rapid development of medical imaging,texture analysis technology continues to improve,which can more accurately judge the nature and prognosis of breast lesions,and provide more information for clinical precise treatment.This review focuses on the application of texture analysis in differentiating benign and malignant breast tumors,predicting molecular subtypes of breast cancer,and evaluating the efficacy of neoadjuvant chemotherapy for breast cancer.

Trastuzumab emtansine(T-DM1)is an antibody drug conjugate formed by the conjugation of humanized monoclonal antibody trastuzumab with cytotoxic drug DM1 through a linker,which integrates the targeting antibody and the high efficiency of cytotoxic drugs to kill cancer cells,exerts double anti-tumor effect and reduces the toxicity of conventional chemotherapeutic drugs.Several clinical studies have explored the effectiveness and tolerance of T-DM1 in rescue treatment of advanced HER2 positive metastatic breast cancer and adjuvant and neoadjuvant chemotherapy of early HER2 positive breast cancer,and shown a good clinical application prospects.This article briefly reviews the latest clinical research progress of T-DM1 in HER2 positive breast cancer.

About 80% patients with gastric cancer in China are in the advanced stage when they are diagnosed due to the lack of obvious symptoms in the early stage of gastric cancer and the insufficient popularization of routine gastroscopic examination.At present,the clinical treatment of gastric cancer is limited,and the survival rate of surgery alone is only about 20%.Since radiotherapy and chemotherapy failed to significantly improve the survival rate of patients and the toxic and side effects were relatively large,a new treatment method was urgently needed to improve the current situation of high morbidity and mortality of gastric cancer.The current popular targeted therapy is a kind of low-toxicity and high-efficiency treatment that targets relevant biomarkers.At present,the biomarkers of relevant targeted therapy in clinical trials are human epidermal growth factor receptor 2(HER2),vascular endothelial growth factor(VEGF),dense protein-18 splice variant 2(claudin 18.2)and mesenchymal-epithelial transition factor(MET).Trastuzumab,a targeted inhibitor of HER2,is the first molecular targeted drug approved for the treatment of gastric cancer,and MET amplification has been shown to be a poor prognostic factor for gastric cancer.In addition,due to the maturity and popularization of high-throughput sequencing technology in recent years,these biomarkers have been gradually applied to the diagnosis,prognosis and clinical treatment of gastric cancer patients.This review will provide an overview of the current research status of common biomarkers for gastric cancer and their treatment strategies.