Absent in melanoma 2 attenuates proliferation and migration and promotes apoptosis of human colorectal cancer cells by activating P38MAPK signaling pathway

Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.

Glycolytic and fatty acid oxidation genes affect the treatment and prognosis of liver cancer

BACKGROUND Metabolic reprogramming is a feature of tumour cells and is essential to support their rapid proliferation.The glycolytic activity of liver cancer cells is significantly higher than that of normal liver cells,and the rapidly proliferating tumour cells are powered by aerobic glycolysis.Lipid metabolism reprogramming enables tumour cells to meet their needs for highly proliferative growth and is an important driving force for the development of hepatocellular carcinoma(HCC).AIM To explore the influence of different metabolic subtypes of HCC and analyse their significance in guiding prognosis and treatment based on the molecular mechanism of glycolysis and fatty acid oxidation(FAO).METHODS By downloading related data from public databases including the Cancer Genome Atlas(TCGA),the Molecular Signatures Database,and International Cancer Genome Consortium,we utilised unsupervised consensus clustering to divide TCGA Liver Hepatocellular Carcinoma samples into four metabolic subgroups and compared single nucleotide polymorphism,copy number variation,tumour microenvironment,and Genomics of Drug Sensitivity in Cancer and Tumour Immune Dysfunction and Exclusion between different metabolites.The differences and causes of survival and the clinical characteristics between them were analysed,and a prognostic model was established based on glycolysis and FAO genes.Combined with the clinical features,a Norman diagram was created to compare the pros and cons of each model.RESULTS In the four metabolic subgroups,with the increase in glycolytic expression,the median survival of patients showed the worst results,while FAO showed the best.When comparing the follow-up analysis of each group,we considered that the differences between them might be related to reactive oxygen species,somatic copy number variation of key genes,and immune microenvironment.It was also found that the FAO group and the low-risk group had better efficacy and response to immune checkpoint blockade treatment and anti-tumour drugs.CONCLUSION There are obvious differences in genes,chromosomes,and clinical characteristics between metabolic subgroups.The establishment of a prognostic model could predict patient prognosis and guide clinical treatment.

Mature Cystic Teratoma of the Suprasternal Fossa in an Adult: Report of Case

Teratomas have been reported to occur in multiple organ regions, and are less common in non-gonadal regions, such as the neck and chest, than in gonadal and midline regions of the body, such as ovaries and testis. Cases have been reported of a large teratoma of the anterior mediastinum extending to the neck, causing symptoms such as dyspnea, which can be quickly detected by Ultrasound, and patients can be quickly treated. In adults, primary teratoma at the suprasternal foss that not accumulate thyroid gland upward and not invade the mediastinum are rare, usually have no obvious clinical symptoms and are found in most patients by chance. In this literature, we report a rare case of mature cystic teratoma in the suprasternal fossa of a 33-year-old male. Preoperative ultrasonography showed a superior sternal fossa tumor with less calcification and more adipose tissue. The final pathologic diagnosis was mature cystic teratoma through open surgery of the suprasternal neck incision. The patient was followed up for 9 months and there was no recurrence. We believe that the suprasternal notch approach is a safe and effective method for the treatment of mature teratoma without protruding into the superior mediastinum.

Influence of adriamycin on changes in Nanog, Oct-4, Sox2, ARID1 and Wnt5b expression in liver cancer stem cells

AIM:To determine the influence of Adriamycin(ADM)on the changes in Nanog,Oct4,Sox2,as well as,in ARID1 and Wnt5b expression in liver cancer stem cells.METHODS:The MHCC97-L and HCCLM3 liver cancer cell lines were selected as the cell models in this study,and were routinely cultured.The 50%lethal dose(LD50)in the cell lines was detected by the MTT assay.Expression changes in liver cancer stem cell related genes(Nanog,Oct-4,Sox2,ARID1,and Wnt5b)were detected by western blot following treatment with ADM(LD50).RESULTS:The LD50 of ADM in MHCC97-L cells was lower than that in HCCLM3 cells(0.4123±0.0236μmol/L vs 0.5259±0.0125μmol/L,P<0.05).Wnt5b and Nanog were expressed in both MHCC97-L and HCCLM3 cells,while only Sox2 was expressed in HCCLM3cells.However,neither ARID1A nor Oct4 was detected in these two cell lines.Genes,related to the stem cells,showed different expression in liver cancer cells with different metastatic potential following treatment with ADM(LD50).Wnt5b protein increased gradually within4 h of ADM(LD50)treatment,while Nanog decreased(P<0.05).After 12 h,Wnt5b decreased gradually,while Nanog increased steadily(P<0.05).In addition,only Sox2 was expressed in HCCLM3 cells with high metastatic potential following ADM(LD50)treatment.The expression of Sox2 increased gradually with ADM(LD50)in HCCLM3 cells(P<0.05).CONCLUSION:ADM increased the death rate of MHCC97-L and HCCLM3 cells,while the growth suppressive effect of ADM was higher in MHCC97-L cells than in HCCLM3 cells.

Novel risk scoring system for prediction of pancreatic fistula after pancreaticoduodenectomy

BACKGROUND The available prediction models for clinically relevant postoperative pancreatic fistula (CR-POPF) do not incorporate both preoperative and intraoperative variables. AIM To construct a new risk scoring system for CR-POPF that includes both preoperative and intraoperative factors. METHODS This was a retrospective study of patients who underwent pancreaticoduodenectomy (PD) or pylorus-preserving PD (PPPD) between January 2011 and December 2016 at the First Affiliated Hospital of Soochow University. Patients were divided into a study (01/2011 to 12/2014) or validation (01/2015 to 12/2016) group according to the time of admission. POPF severity was classified into three grades: Biochemical leak (grade A) and CR-POPF (grades B and C). Logistic regression was used to create a predictive scoring system. RESULTS Preoperative serum albumin ≥ 35 g/L [P = 0.032, odds ratio (OR)= 0.92, 95% confidence interval (CI): 0.85-0.99], hard pancreatic texture (P = 0.004, OR = 0.25, 95%CI: 0.10-0.64), pancreatic duct diameter ≥ 3 mm (P = 0.029, OR = 0.50, 95%CI: 0.27-0.93), and intraoperative blood loss ≥ 500 mL (P = 0.006, OR = 1.002, 95%CI:1.001-1.003) were independently associated with CR-POPF. We established a 10-point risk scoring system to predict CR-POPF. The area under the curve was 0.821 (95%CI: 0.736-0.905) and the cut-off value was 3.5. Including drain amylase levels improved the predictive power of the model. CONCLUSION This study established a 10-point scoring system to predict CR-POPF after PD/PPPD using preoperative and intraoperative parameters. Ultimately, this system could be used to distinguish between high- and low-risk populations in order to facilitate timely interventions after PD.

MiR-144 Inhibits Cell Proliferation of Renal Cell Carcinoma by Targeting MTOR

Micro RNAs（mi RNAs） modulate the expression of tumorigenesis-related genes and play important roles in the development of various types of cancers. It has been reported that mi R-144 is dysregulated and involved in multiple malignant tumors, but its role in renal cell carcinoma（RCC） remains elusive. In this study, we demonstrated mi R-144 was significantly downregulated in human RCC. The decreased mi R-144 correlated with tumor size and TNM stage. Moreover, overexpression of mi R-144 in vitro suppressed RCC cell proliferation and G2 transition, which were reversed by inhibition of mi R-144. Bioinformatic analysis predicted that m TOR was a potential target of mi R-144, which was further confirmed by dual luciferase reporter assay. Additionally, the examination of clinical RCC specimens revealed that mi R-144 was inversely related to m TOR. Furthermore, knocking down m TOR with si RNA had the same biological effects as those of mi R-144 overexpression in RCC cells, including cell proliferation inhibition and S/G2 cell cycle arrest. In conclusion, our results indicate that mi R-144 affects RCC progression by inhibiting m TOR expression, and targeting mi R-144 may act as a novel strategy for RCC treatment.

Experience on Diagnosis and Treatment of Strangulated Intestinal Obstruction Caused by Mesentery Vein Thrombosis on Account of Portal Hypertension

In the present study, to investigate diagnosis and treatment of strangulated intestinal obstruction caused by mesentery vein thrombosis on account of portal hypertension, the data in twelve patients with this disease from 1998 to 2008 were analyzed. All patients presented abdominal pain and vomiting and were confirmed strangulated intestinal obstruction caused by mesentery thrombosis with operation. In this group, nine patients underwent part of small intestine excision, and three patients underwent open-closed operation because of the whole small intestine necrosis caused by intensive mesentery thrombosis. Five patients died after operation. The diagnosis of strangulated intestinal obstruction caused by mesentery thrombosis was difficult because of the slow disease processes and severe outcomes. It is necessary to take some measures to get over the dangers duration after operation.

Management and outcomes of gastric leak after sleeve gastrectomy:results from the 2010-2020 national registry

Background:Management of gastric leak after sleeve gastrectomy(SG)is challenging due to its unpredictable outcomes.We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting.Methods:To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry.A cumulative sum analysis was used to identify a fitting curve of gastric leak rate.The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes.The logistic regression analysis was conducted to determine the predictors of acute leaks.Results:A total of 78 cases of SG leaks were collected with an incidence of 0.5%(78/15,721)from this registry(6 patients who had the primary SG in non-participating centers).After accumulating 260 cases in a bariatric surgery center,the leak rate decreased to a stably low value of under 1.17%.The significant differences presented in sex,waist circumference,and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population(P=0.005,=0.026,<0.001,and=0.001,respectively).Moreover,83.1%(59/71)of the leakage was near the esophagogastric junction region.Leakage healed in 64(88.9%,64/72)patients.The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months,respectively.Acute leak(38/72,52.8%)was the predominant type with a cumulative reoperation rate>50%,whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment(P=0.013).Precise dissection in the His angle area was independently associated with a lower acute leak rate,whereas preservation≥2 cm distance from the His angle area was an independent risk factor.Conclusions:Male sex,elevated waist circumference,hypoproteinaemia,and type 2 diabetes are risk factors of gastric leaks after SG.Optimizing surgical techniques,including precise dissection of His angle area and preservation of smaller gastric fundus,should be suggested to prevent acute leaks.

TBL1XR1 induces cell proliferation and inhibit cell apoptosis by the PI3K/AKT pathway in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC) is one of the deadliest solid tumors. Identification of diagnostic and therapeutic biomarkers for PDAC is urgently needed. Transducin(β)-like 1 X-linked receptor 1(TBL1 XR1) has been linked to the progression of various human cancers. Nevertheless, the function and role of TBL1 XR1 in pancreatic cancers are unclear.AIM To elucidate the function and potential mechanism of TBL1 XR1 in the development of PDAC.METHODS Ninety patients with histologically-confirmed PDAC were included in this study. PDAC tumor samples and cell lines were used to determine the expression of TBL1 XR1. CCK-8 assays and colony formation assays were carried out to assess PDAC cell viability. Flow cytometry was performed to measure the changes in the cell cycle and cell apoptosis. Changes in related protein expression were measured by western blot analysis. Animal analysis was conducted to confirm the impact of TBL1 XR1 in vivo.RESULTS Patients with TBL1 XR1-positive tumors had worse overall survival than those with TBL1 XR1-negative tumors. Moreover, we found that TBL1 XR1 strongly promoted PDAC cell proliferation and inhibited PDAC cell apoptosis. Moreover, knockdown of TBL1 XR1 induced G0/G1 phase arrest. In vivo animal studies confirmed that TBL1 XR1 accelerated tumor cell growth. The results of western blot analysis showed that TBL1 XR1 might play a key role in regulating PDAC cell proliferation and apoptosis via the PI3 K/AKT pathway.CONCLUSION TBL1 XR1 promoted PDAC cell progression and might be an effective diagnostic and therapeutic marker for pancreatic cancer.

Why MUC16 mutations lead to a better prognosis:A study based on The Cancer Genome Atlas gastric cancer cohort

BACKGROUND MUC16,encoding cancer antigen 125,is a frequently mutated gene in gastric cancer.In addition,MUC16 mutations seem to result in a better prognosis in gastric cancer.However,the mechanisms that lead to a better prognosis by MUC16 mutations have not yet been clarified.AIM To delve deeper into the underlying mechanisms that explain why MUC16 mutations signal a better prognosis in gastric cancer.METHODS We used multi-omics data,including mRNA,simple nucleotide variation,copy number variation and methylation data from The Cancer Genome Atlas,to explore the relationship between MUC16 mutations and prognosis.Cox regression and random survival forest algorithms were applied to search for hub genes.Gene set enrichment analysis was used to elucidate the molecular mechanisms.Single-sample gene set enrichment analysis and“EpiDISH”were used to assess immune cells infiltration,and“ESTIMATE”for analysis of the tumor microenvironment.RESULTS Our study found that compared to the wild-type group,the mutation group had a better prognosis.Additional analysis indicated that the MUC16 mutations appear to activate the DNA repair and p53 pathways to act as an anti-tumor agent.We also identified a key gene,NPY1R(neuropeptide Y receptor Y1),which was significantly more highly expressed in the MUC16 mutations group than in the MUC16 wild-type group.The high expression of NPY1R predicted a poorer prognosis,which was also confirmed in a separate Gene Expression Omnibus cohort.Further susceptibility analysis revealed that NPY1R might be a potential drug target for gastric cancer.Furthermore,in the analysis of the tumor microenvironment,we found that immune cells in the mutation group exhibited higher anti-tumor effects.In addition,the tumor mutation burden and cancer stem cells index were also higher in the mutation group than in the wild-type group.CONCLUSION We speculated that the MUC16 mutations might activate the p53 pathway and DNA repair pathway:alternatively,the tumor microenvironment may be involved.

Kyphoplasty versus vertebroplasty for the treatment of malignant vertebral compression fractures caused by metastases： a retrospective study

Background There are few comparative studies regarding kyphoplasty （KP） and vertebroplasty （VP） for the treatment of painful vertebral compression fractures （VCF） in patients with cancer. The purpose of this study is to retrospectively compare KP with VP in pain improvement, cement leakage incidence, and the cost of treatment of malignant VCE Methods We performed a retrospective study of clinical data for 80 patients with multiple spinal metastases, treated with KP in 42 cases and VP in 38. Visual analog scale （VAS） scores were collected pre-operatively, post-operatively, at 1 month, 6 months, and 1 year after treatment. Cement leakage was identified using fluoroscopy and CT scan. Total cost per patient was also collected. Results There was a significant difference between the pre- and post-operative VAS scores （7.4＋2.0 to 3.8＋1.6, P 〈0.001 in the KP group; 6.7＋2.4 to 3.7＋1.4, P 〈0.001 in the VP group）, and was maintained at 1-year follow-up （3.2＋1.4 in the KP group, 3.1＋1.3 in the VP group）. However, the difference in VAS score between these two groups was insignificant at baseline and every follow-up assessment post-operatively （P 〉0.05）. The incidence of cement leakage in the KP group was lower than that of the VP group （16.9% （14/83） vs 30.3% （23/76）, P 〈0.05）. However, none of the patients developed any symptoms. The length of postoperative hospital stay in the VP group was shorter than that of the KP group （（2.4＋1.3） vs （5.3＋1.9） days, P 〈0.05）. Total hospital cost in the KP group was much higher than that of the VP group （RMB Yuan 8 492_＋3 332 vs RMB Yuan 3 173~1 341, P〈0.01）. Conclusions VP and KP are both effective in providing pain relief for patients with cancer-related VCF. KP provides no greater degree of pain improvement. KP is associated with a lower rate of cement leakage compared with VP. VP is associated with lower cost and shorter postoperative hospital stay in China.

TLR9 agonist enhances radiofrequency ablation-induced CTL responses, leading to the potent inhibition of primary tumor growth and lung metastasis

Radiofrequency ablation(RFA)is the most common approach to thermal ablation for cancer therapy.Unfortunately,its efficacy is limited by incomplete ablation,and further optimization of RFA is required.Here,we demonstrate that incubation at 65°C triggers more EG7 tumor cell death by necrosis than treatment at 45°C,and the 65°C-treated cells are more effective at inducing antigen-specific CD8^(+)cytotoxic T lymphocyte(CTL)responses after injection in mice than the 45°C-treated ones.Dendritic cells(DCs)that phagocytose 65°C-treated EG7 cells become mature with upregulated MHCII and CD80 expression and are capable of efficiently inducing effector CTLs in mouse tumor models.RFA(65°C)therapy of EG7 tumors induces large areas of tumor necrosis and stimulates CTL responses.This leads to complete regression of small(~100 mm^(3))tumors but fails to suppress the growth of larger(~350 mm^(3))tumors.The administration of the Toll-like receptor-9(TLR9)agonist unmethylated cytosine-phosphorothioate-guanine oligonucleotide(CpG)to DCs phagocytosing 65°C-treated EG7 cells enhances the expression of MHCII and CD40 on DCs as well as DC-induced stimulation of CTL responses.Importantly,the intratumoral administration of CpG following RFA also increases the frequencies of tumor-associated immunogenic CD11b−CD11c^(+)CD103^(+)DC2 and CD11b+F4/80+MHCII+M1 macrophages and increases CD4^(+)and CD8^(+)T-cell tumor infiltration,leading to enhanced CD4^(+)T cell-dependent CTL responses and potent inhibition of primary RFA-treated or distant untreated tumor growth as well as tumor lung metastasis in mice bearing larger tumors.Overall,our data indicate that CpG administration,which enhances RFA-induced CTL responses and ultimately potentiates the inhibition of primary tumor growth and lung metastasis,is a promising strategy for improving RFA treatment,which may assist in optimizing this important cancer therapy.

IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitis in vitro

AIM To investigate the role of interferon regulatory factor 5(IRF5) in reversing polarization of lung macrophages during severe acute pancreatitis(SAP) in vitro.METHODS A mouse SAP model was established by intraperitoneal(ip) injections of 20 μg/kg body weight caerulein. Pathological changes in the lung were observed by hematoxylin and eosin staining. Lung macrophages were isolated from bronchoalveolar lavage fluid. The quantity and purity of lung macrophages were detectedby fluorescence-activated cell sorting and evaluated by real-time polymerase chain reaction(RT-PCR). They were treated with IL-4/IRF5 specific siR NA(IRF5 siR NA) to reverse their polarization and were evaluated by detecting markers expression of M1/M2 using RTPCR.RESULTS SAP associated acute lung injury(ALI) was induced successfully by ip injections of caerulein, which was confirmed by histopathology. Lung macrophages expressed high levels of IRF5 as M1 phenotype during the early acute pancreatitis stages. Reduction of IRF5 expression by IRF5 siR NA reversed the action of macrophages from M1 to M2 phenotype in vitro. The expressions of M1 markers, including IRF5(S + IRF5 siR NA vs S + PBS, 0.013 ± 0.01 vs 0.054 ± 0.047, P < 0.01), TNF-α(S + IRF5 siR NA vs S + PBS, 0.0003 ± 0.0002 vs 0.019 ± 0.018, P < 0.001), iN OS(S + IRF5 siR NA vs S + PBS, 0.0003 ± 0.0002 vs 0.026 ± 0.018, P < 0.001) and IL-12(S + IRF5 si RNA vs S + PBS, 0.000005 ± 0.00004 vs 0.024 ± 0.016, P < 0.001), were decreased. In contrast, the expressions of M2 markers, including IL-10(S + IRF5 siR NA vs S + PBS, 0.060 ± 0.055 vs 0.0230 ± 0.018, P < 0.01) and Arg-1(S + IRF5 siR NA vs S + PBS, 0.910 ± 0.788 vs 0.0036 ± 0.0025, P < 0.001), were increased. IRF5 si RNA could reverse the lung macrophage polarization more effectively than IL-4.CONCLUSION Treatment with IRF5 siR NA can reverse the pancreatitisinduced activation of lung macrophages from M1 phenotype to M2 phenotype in SAP associated with ALI.

Enhanced anti-tumor immunity ex vivo induced by GM-CSF gene transducted dendritic cell vaccine

学习的目的是调查是否的目的树枝状的房间(DC ) 先锋，由 chemokine ligand 的注射招募了 3 (CCL3 ) ，在 granulocyte 巨噬细胞殖民地刺激以后导致提高的反肿瘤免疫在老鼠前 vivo 的因素(GM-CSF ) transfection。615 只老鼠经由尾巴静脉与 CCL3 被注射的方法。刚孤立的 B220-CD11c+ 房间与 cytokines 是有教养的。为 adenoviral (广告) 调停的基因 transduction， DC 是在感染(MOI ) 的复合的不同比率的转移 AdGM-CSF 基因决定最佳的基因 transfection 条件，并且在 transfection 以后检测 GM-CSF 的表示。GM-CSF 修改基因的 DC 的变化被词法观察，显型分析，和混合淋巴细胞反应(MLR ) 分析。DC 被装载，胃的癌症抗原由冻结并且融化的方法获得了。刺激 DC 种痘导致了 T 淋巴细胞，和 T 房间的杀死的效果到胃的癌症房间是由 MTT 的 assayed。INF- 生产与 INF- ELISA 工具包被决定。结果 B220-CD11c+ 房间数字在 CCL3 注射以后增加了。ELISA 结果证明在 GM-CSF 基因修正以后， DC 能生产 GM-CSF 的高水平。DC 是什么时候，在等于 1:100 的 MOI 转移了 AdGM-CSF 基因，在文化上层清液的 GM-CSF 水平到达了浸透[(130.00 ???????????????? ″ ? 匠牵楶楶? 僚 ??? 吗？？

Hemobilia with acute pancreatitis secondary to biliary tract infection

Hemobilia is a rare medical condition with variety of etiologies.Among them,two in thirds are iatrogenic.Hemobilia combined with acute pancreatitis is unusual.Herein we reported a case of hemobilia with acute pancreatitis secondary to biliary tract infection.A 76-year-old male patient had intermittent abdominal pain for 2 days,which was aggravated for 1 day.He was admitted to the Emergency Department on August 29,2017.The patient developed paroxysmal abdominal pain after consuming greasy foods,accompanied by nausea.The physical examination revealed the following:temperature 37.0°C,pulse 76 bpm,respiratory rate 19 per minute,blood pressure 164/77 mmHg;no jaundice;abdominal distention;and mild total abdominal tenderness,mainly located in the left upper abdomen.Murphy’s sign was positive.Urgent abdominal ultrasound showed postprandial gallbladder emptying,gallbladder stones,unclear gallbladder cavity,and focal hepatic lesions.Hemangioma was suggested.The intrahepatic bile duct was mildly dilated,and the abdominal and pelvic cavity showed no obvious accumulation of fluid.The laboratory findings were as follows:serum amylase 922.1 U/L,white blood cell count 18.2×109/L(neutrophils,83.4%),and hemoglobin 13.8 g/dL.

P53和Bcl-2家族蛋白在胰腺癌中的表达与细胞凋亡的关系(英文)

目的探讨胰腺癌组织(pancreatic carcinoma,PC)中p53和Bcl-2家族(Bcl-2,Bax,BclxL,Bcl-xS)蛋白表达及与细胞凋亡的关系。方法免疫组化法检测35例PC中P53的蛋白表达,将PC分为p53阴性表达组(第1组,n=18)和p53阳性表达组(第2组,n=17);Western blot检测两组PC中P53、Bcl-2,Bax,Bcl-xL和Bcl-xS蛋白表达,TUNEL法检测第1组中凋亡指数(AI)。结果 Bcl-2蛋白在P53阳性PC表达上调,而在P53阴性PC表达下调(P=0.047);Bax和Bcl-xL蛋白在两组PC中表达都明显上调(P=0.274,0.334);Bcl-xS在p53阳性表达PC明显下调,在p53阴性表达组明显上调(P=0.01);在P53阴性和阳性表达PC,AI分别为12.1±2.47和9.1±1.48(P=0.023);Bcl-2家族各成员表达与AI无相关性,而Bcl-2/Bax比率与AI有明显的相关性(P<0.01)。结论 Bcl-2是依赖p53调节的抗凋亡蛋白,Bcl-xS是依赖P53调节的促凋亡蛋白,而P53主要通过调节Bcl-2/Bax比率发挥凋亡调节作用。

Metachronous pulmonary and pancreatic metastases arising from sigmoid colon cancer:A case report

BACKGROUND Metachronous pulmonary and pancreatic metastases from colorectal cancer are rare.The diagnosis of pancreatic metastases is difficult and predominantly relies on computed tomography,pathology and immunohistochemistry.Here,we describe the use of next-generation sequencing(NGS)for determination of the origin of metastasis and prognostic prediction of colorectal cancer.CASE SUMMARY A 59-year-old man was diagnosed with sigmoid adenocarcinoma stage IIA(T3N0M0)and underwent surgery in April 2014,followed by XELOX adjuvant chemotherapy.The patient developed pulmonary metastasis in the right upper lung and underwent surgery in May 2016 without further adjuvant chemotherapy.In May 2018,pancreatic metastasis was found and he underwent pancreaticoduodenectomy.After surgery,he was treated with adjuvant S-1 chemotherapy from June 2018 to March 2019.Histopathological review of the specimens from all three lesions indicated consistent patterns characteristic of colon cancer.Concordant gene mutation profiles were observed across the three lesions that included oncogenic driver mutations most frequently seen in colon cancer(e.g.,APC,TP53,KRAS and FBXW7).Blood circulating tumor(ct)DNA before adjuvant chemotherapy was undetectable with NGS,suggesting a favorable response to chemotherapy.The patient was alive and well at the latest follow-up visit,achieving a disease-free survival of 17 mo.CONCLUSION The genetic profiles of primary tumor,metastases and ctDNA may have clinical value in auxiliary diagnosis,prognosis and therapeutic decision-making.

Dendritic Cell as Therapeutic Vaccines against Tumors and Its Role in Therapy for Hepatocellular Carcinoma

Dendritic cells （DCs） are the most potent professional antigen-presenting cells, and capable of stimulating naive T cells and driving primary immune responses. DCs are poised to capture antigen, migrate to draining lymphoid organs, and after a process of maturation, select antigen-specific lymphocytes to which they present the processed antigen, thereby inducing immune responses. The development of protocols for the ex vivo generation of DCs may provide a rationale for designing and developing DC-based vaccination for the treatment of tumors. There are now several strategies being applied to upload antigens to DCs and manipulate DC vaccines. DC vaccines are able to induce therapeutic and protective antitumor immunity. Numerous studies indicated that hepatocellular carcinoma （HCC） immunotherapies utilizing DC-presenting tumor-associated antigens could stimulate an antitumour T cell response leading to clinical benefit without any significant toxicity. DC-based tumor vaccines have become a novel immunoadjuvant therapy for HCC. Cellular ＆ Molecular Immunology. 2006;3（3）：197-203.

Collagen membrane alleviates peritendinous adhesion in the rat Achilles tendon injury model

Background Tendon adhesion is one of the most common causes of disability following tendon surgery. Therefore, prevention of peritendinous adhesion after surgical repair of tendon is a major challenge. The aim of this study was to explore the possible application of a collagen membrane for the prevention or attenuation of peritendinous adhesions. Methods Sprague-Dawley （SD） rat Achilles tendon was cut and sutured by a modified Kessler＇s technique with or without the collagen membrane wrapped. Macroscopic, morphological and biomechanical evaluations were applied to examine the recovery of the injured tendon at 4 and 8 weeks after surgery. Results The surgery group wrapped by collagen membranes had a better outcome than the group with surgery repair only. In the collagen membrane-treated group, less adhesion appeared, stronger tensile strength was detected, and more tendon fibers and collagen I expression were observed morphologically. Conclusion Wrapping the tendon with a collagen membrane may be an efficient approach for tendon repair and preventing tendon adhesion after its ruptures.