BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GI...BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GIST(17 male and 2 female,median age 62 years).GC was most often located in the lower third of the stomach.GIST was diagnosed preoperatively in four patients.GIST was most often located in the gastric body(n=8,42%).The most common growth pattern in GIST was extraluminal(n=12,63%).The positive expression rates of CD117 and CD34 in GIST were 100% and 95%,respectively.Most patients with GIST(n=17,89%)were very low or low risk.There was no recurrence of GIST during follow-up.The 3-year cumulative survival rate was 73.9%,and the 5-year cumulative survival rate was 59.2%.The combined analysis of this study and literature reports(47 reports,157 patients)found that GC and GIST were usually located in the lower third(42%)and middle third(51%)of the stomach.GC was usually early(stage I:42%),poorly differentiated(42%)intestinal-type adenocarcinoma(51%).GISTs were primarily small in diameter(median:1.2 cm)and very low or low risk(89%).CONCLUSION Synchronous GC and GIST may not be rare.They have specific clinicopathological characteristics,and may have mutual inhibition in pathogenesis and progression.展开更多
BACKGROUND: Some scholars think that hypertension is the major risk factor to cause Binswanger disease (BD), however, BD is also found in some persons with normal blood pressure, so we presume that some other factors,...BACKGROUND: Some scholars think that hypertension is the major risk factor to cause Binswanger disease (BD), however, BD is also found in some persons with normal blood pressure, so we presume that some other factors, such as diabetes mellitus, hyperlipemia, coronary heart disease and transient ischemic attacks and so on, might participant in the onset of BD. OBJECTIVE: To comparatively observe the difference in accompanying diseases, transcranial doppler (TCD) performance, blood glucose and blood lipid level between BD patients and healthy subjects who received health examination, and between BD patients with different disease condition. DESIGN: Case-control analysis. SETTING: Department of Emergency, Qingdao Municipal Hospital. PARTICIPANTS: Totally 126 patients with BD, 65 male and 61 female, aged from 67 to 85 years old, who hospitalized in the Medical School Hospital of Qingdao University and Qingdao Municipal People’s Hospital, were chosen, serving as BD patients group. All the patients met the clinical diagnostic criteria of BD introduced by Bennett et al. Another 126 persons, 65 male and 61 female, aged ranging from 67 to 80 years, who received health examination in the same hospital, were homeochronously chosen, serving as control group. Informed consents were obtained from all the subjects. METHODS: After being admitted, all the subjects including BD patients and persons who homeochronously received health examination in the same hospital were given examinations of blood pressure, blood lipid, blood glucose, electrocardiogram (ECG) and TCD. Fifty-seven patients with BD were in the stable period and 69 in the progressive period (Stable period: no local or subcortical function disorder found, and no changes in the range of white matter lesion showed by CT and/or MRI in recent 3 months; Progressive period: with local or subcortical function disorder and increase in the range of white matter lesion showed by CT and/or MRI in recent 3 months). According to intimal thickening of carotid artery and vertebral artery preformed by TCD, BD was graded as mild intimal thickening (< 1.1 mm), moderate intimal thickening (1.1 to 1.2 mm) and severe intimal thickening (> 1.2 mm). MAIN OUTCOME MEASURES: Comparison of the ratio of BD patients with accompanied diabetes mellitus, hyperlipemia, coronary heart disease and transient ischemic attacks, TCD performance, blood glucose and blood lipid level between BD patients group and control group, and among BD patients with various disease conditions. RESULTS: Totally 126 BD patients and 126 subjects who received health examination all participated in the result analysis. Intergroup comparison: ①The ratio of BD patients with accompanied hypertension, diabetes mellitus, hyperlipemia, transient ischemic attacks and coronary heart disease was 91.3%, 46.8%, 42.9%, 81.7% and 46.0% respectively in the BD patients group, and that was 36.5%, 17.5%, 15.9%, 34.1% and 34.1%, respectively in the control group. Significant difference existed between two groups (χ2=86.201,24.907,25.660,58.620,9.900, P < 0.01).②Compared with control group, anterior, middle cerebral and vertebrobasilar arteriosclerosis and insufficient cerebral blood supply existed significantly in BD patients with different disease condition(χ2=40.34,7.585,15.429, P < 0.01).③ Compared with control group, the level of blood glucose, total cholesterol and triglyceride of BD patients increased significantly (t=6.939,3.891,3.711,P < 0.01). Comparison among BD patients with different disease condition: ① Compared with stable period, transient ischemic attacks and coronary heart disease were found much in the BD patients at progressive period , with significant difference (χ2=7.196,13.517,P < 0.01).② Mild arteriosclerosis at stable period was found in 17 cases, and significant difference existed compared with progressive period (χ2=6.523,P < 0.05).③ There was no significant difference in the blood glucose and blood lipid level (t=1.755 6,0.583 1,0.824 6, P > 0.05). CONCLUSION: Hypertension, cerebral arteriosclerosis, diabetes mellitus, hyperlipemia, coronary heart disease and transient ischemic attacks have important effects on the onset of BD; Transient ischemic attacks and coronary heart disease can worsen the symptoms of BD patients.展开更多
Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify onco...Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto展开更多
Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study desc...Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells.The GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 model.Immunofluorescence analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the model.Compared with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and genes.Moreover,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three models.In addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude mice.Immunohistochemical evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was higher.This research therefore acts as a foundation for the application of 3DP-7721 models in drug development research.展开更多
Global energy structure is experiencing the third transition from fossil energy to non-fossil energy,to solve future energy problems,cope with climate change,and achieve net-zero emissions targets by 2050.Hydrogen is ...Global energy structure is experiencing the third transition from fossil energy to non-fossil energy,to solve future energy problems,cope with climate change,and achieve net-zero emissions targets by 2050.Hydrogen is considered to be the most potential clean energy in this century under the background of carbon neutrality.At present,the industrial methods for producing hydrogen are mainly by steam-hydrocarbon(such as coal and natural gas)reforming and by electrolysis of water,while the exploration and development of natural hydrogen had just started.According to this literature review:(1)Natural hydrogen can be divided into three categories,including free hydrogen,hydrogen in inclusions and dissolved hydrogen;(2)natural hydrogen could be mainly from abiotic origins such as by deep-seated hydrogen generation,water-rock reaction or water radiolysis;(3)natural hydrogen is widely distributed and presents great potential,and the potential natural hydrogen sources excluding deep source of hydrogen is about(254±91)×10^(9) m^(3)/a according to a latest estimate;(4)at present,natural hydrogen has been mined in Mali,and the exploration and development of natural hydrogen has also been carried out in Australia,Brazil,the United States and some European countries,to find many favorable areas and test some technical methods for natural hydrogen exploration.Natural hydrogen is expected to be an important part of hydrogen energy production in the future energy pattern.Based on a thorough literature review,this study introduced the origin,classification,and global discovery of natural hydrogen,as well as summarized the current global status and discussed the possibility of natural hydrogen exploration and development,aiming to provide reference for the future natural hydrogen exploration and development.展开更多
Background: MicroRNA?506(miR?506) has been reported to function in several tumors as a tumor suppressor gene or oncogene. However, the expression and role of miR?506 in pancreatic ductal adenocarcinoma(PDAC) remains u...Background: MicroRNA?506(miR?506) has been reported to function in several tumors as a tumor suppressor gene or oncogene. However, the expression and role of miR?506 in pancreatic ductal adenocarcinoma(PDAC) remains unclear. In this study, we aimed to evaluate the phenotype of miR?506 in PDAC.Methods: Using mi RNA in situ hybridization, we examined the expression of miR?506 in 113 PDACs and 87 paired normal pancreatic tissues. We evaluated mi R?506 expression in PDAC cells, normal pancreatic ducts, and acinus/islands, and we analyzed the associations between miR?506 expression and the clinicopathologic characteristics of PDAC patients.Results: miR?506 expression was higher in PDAC than in matched normal pancreatic ductal cells(P < 0.001). On the other hand, the combined group of well and moderately diferentiated PDACs showed higher levels of mi R?506 than the poorly diferentiated ones(P = 0.023). Moreover, mi R?506 expression was negatively associated with pathologic T category(P = 0.004) and lymph node metastasis(P = 0.033), suggesting that mi R?506 might inhibit the progression of PDAC.Conclusions: Our results suggest that mi R?506 either plays a role as an oncogene in the tumorigenesis and a tumor suppressor in the progression or serves as a house?keeping, tumor?suppressing mi RNA, whose expression can be activated by oncogenic signals in early development to hinder the progression of PDAC.展开更多
AIM:To review the clinicopathological characteristics of concurrent gastrointestinal stromal tumors(GISTs) and gastric adenocarcinoma.METHODS:We retrospectively analyzed eight cases of synchronous adenocarcinoma and G...AIM:To review the clinicopathological characteristics of concurrent gastrointestinal stromal tumors(GISTs) and gastric adenocarcinoma.METHODS:We retrospectively analyzed eight cases of synchronous adenocarcinoma and GIST in the stomach that had been surgically resected with curative intent between March 2003 and December 2008 in Xinhua hospital and Ruijin hospital.The adenocarcinoma was determined to be the primary tumor based on the histological features.The GIST cells were diffusely and strongly positive for CD34 and CD117.RESULTS:The patients were six men and two women aged 47-80 years(average,68.6 years).GIST was preoperatively detected in only one patient.The average sizes of the gastric adenocarcinomas and GISTs were 6.000 ± 2.6186 cm and 1.825 ± 1.4370 cm,respectively.All GISTs were very low-or low-risk lesions that were detected during evaluation,staging,operation or follow-up for gastric adenocarcinoma.CONCLUSION:We hypothesized that the stomach was influenced by the same unknown carcinogen,resulting in a simultaneous proliferation of different cell lines(epithelial and stromal cell).展开更多
Many digestive system malignant tumors are characterized by high incidence and mortality rate.Increasing evidence has revealed that the tumor microenvironment(TME)is involved in cancer initiation and tumor progression...Many digestive system malignant tumors are characterized by high incidence and mortality rate.Increasing evidence has revealed that the tumor microenvironment(TME)is involved in cancer initiation and tumor progression.Tumor-associated macrophages(TAMs)are a predominant constituent of the TME,and participate in the regulation of various biological behaviors and influence the prognosis of digestive system cancer.TAMs can be mainly classified into the antitumor M1 phenotype and protumor M2 phenotype.The latter especially are crucial drivers of tumor invasion,growth,angiogenesis,metastasis,immunosuppression,and resistance to therapy.TAMs are of importance in the occurrence,development,diagnosis,prognosis,and treatment of common digestive system malignant tumors.In this review,we summarize the role of TAMs in common digestive system malignant tumors,including esophageal,gastric,colorectal,pancreatic and liver cancers.How TAMs promote the development of tumors,and how they act as potential therapeutic targets and their clinical applications are also described.展开更多
Abstract China used to have great urban rural disparity in socioeconomic development. Since the late 1980s, rapid socioeconomic development and urbanization have been taking place in rural settings. It is epidemiologi...Abstract China used to have great urban rural disparity in socioeconomic development. Since the late 1980s, rapid socioeconomic development and urbanization have been taking place in rural settings. It is epidemiologically established that cancer scale and profile will transit as economy prospers and urbanization develops. However, there are few published studies reporting what changes are undergoing in cancer pattern in Chinese rural settings. Population-based tumor registration data collected by us in urban Shijiazhuang city (available for 2,374,827 people in 2012) and in rural Shexian County (available for 408,995 people since 2000) were used for urban rural comparison of age standardized incidence rate (ASIR) of westernization-related cancers in 2012, and the trend of biennial ASIR of these cancers for 2000-2015 in Shexian County was examined following a decade of rapid socioeconomic development and urbanization. From 1988-2015, the Gross Domestic Product per Capita (GDP) in rural Shexian County increased from 860 to 3000 US$, and urbanization rate from 22.4% to 54.8%. The biennial ASIRs of lung, colorectal, gallbladder cancer and leukemia in both sexes, and that of breast, ovary, thyroid, and kidney cancer in women increased significantly from 2000 - 2015. The increase from 2000-2001 to 2014-2015 in man and women for lung cancer was from 15.9 to 34.7 per 105 (P = 0.05) and 9.6 to 16.7 (P = 0.00), for colorectal cancer from 6.6 to 15.9 (P = 0.00) and 4.0 to 11.7 (P = 0.00), for gallbladder cancer from 0.1 to 2.4 (P = 0.00) and 0.3 to 2.7 (P = 0.00), for leukemia from 2.8 to 7.7 (P = 0.00) and 2.3 to 6.2 (P = 0.00);and in women for cancer of breast from 2.8 to 17.3 (P = 0.00), kidney from 0.2 to 2.4 (P = 0.00), ovary from 0.2 to 4.3 (P = 0.00), and thyroid from 0.2 to 4.2 (P = 0.00). Notwithstanding these increases, their ASIRs in 2012 in Shexian County were still significantly lower than that in Shijiazhuang city. Westernization-related cancer is increasing rapidly in rural China. Comprehensive measures are needed to strengthen prevention to ensure sustainable development.展开更多
Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy ...Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.展开更多
Postoperative adhesion(POA)widely occurs in soft tissues and usually leads to chronic pain,dysfunction of adjacent organs and some acute complications,seriously reducing patients’quality of life and even being life-t...Postoperative adhesion(POA)widely occurs in soft tissues and usually leads to chronic pain,dysfunction of adjacent organs and some acute complications,seriously reducing patients’quality of life and even being life-threatening.Except for adhesiolysis,there are few effective methods to release existing adhesion.However,it requires a second operation and inpatient care and usually triggers recurrent adhesion in a great incidence.Hence,preventing POA formation has been regarded as the most effective clinical strategy.Biomaterials have attracted great attention in preventing POA because they can act as both barriers and drug carriers.Nevertheless,even though much reported research has been demonstrated their efficacy on POA inhibition to a certain extent,thoroughly preventing POA formation is still challenging.Meanwhile,most biomaterials for POA prevention were designed based on limited experiences,not a solid theoretical basis,showing blindness.Hence,we aimed to provide guidance for designing anti-adhesion materials applied in different soft tissues based on the mechanisms of POA occurrence and development.We first classified the postoperative adhesions into four categories according to the different components of diverse adhesion tissues,and named them as“membranous adhesion”,“vascular adhesion”,“adhesive adhesion”and“scarred adhesion”,respectively.Then,the process of the occurrence and development of POA were analyzed,and the main influencing factors in different stages were clarified.Further,we proposed seven strategies for POA prevention by using biomaterials according to these influencing factors.Meanwhile,the relevant practices were summarized according to the corresponding strategies and the future perspectives were analyzed.展开更多
Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been p...Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors(GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and m RNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin(PI3K/AKT/m TOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/m TOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/m TOR pathway and the development of GISTs.展开更多
Objective: To study the value of gastroenterultrasound developer in diagnosis of the stomach tumor. Methods: 38 patients who diagnosed as stomach tumor by gastroscopy were chosen, and their images before and after by ...Objective: To study the value of gastroenterultrasound developer in diagnosis of the stomach tumor. Methods: 38 patients who diagnosed as stomach tumor by gastroscopy were chosen, and their images before and after by using gastroenterultrasound developer were compared. Results: The difference between the detectable rate of stomach tumor before and after by using gastroenterultrasound developer was significant (P < 0.01). Conclusion: Gastroenterultrasound developer has a high diagnostic value in diagnosis of the stomach tumor.展开更多
Due to the aging of the population and despite the enormous scientific effort,Alzheimer's disease remains one of the biggest medical and pharmaceutical challenges in current medicine.Novel insights highlight the i...Due to the aging of the population and despite the enormous scientific effort,Alzheimer's disease remains one of the biggest medical and pharmaceutical challenges in current medicine.Novel insights highlight the importance of neuroinflammation as an undeniable player in the onset and progression of Alzheimer's disease.Tumor necrosis factor is a master inflammatory cytokine that signals via tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2,but that also regulates several brain functions in health and disease.However,clinical trials investigating drugs that interfere with the tumor necrosis factor pathway in Alzheimer's disease led to inconclusive results,partially because not only the pro-inflammatory tumor necrosis factor/tumor necrosis factor receptor 1,but also the beneficial tumor necrosis factor/tumor necrosis factor receptor 2 signaling was antagonized in these trials.We recently found that tumor necrosis factor is the main upregulated cytokine in the choroid plexus of Alzheimer's disease patients,signaling via tumor necrosis factor receptor 1.In agreement with this,choroidal tumor necrosis factor/tumor necrosis factor receptor 1 signaling was also upregulated in different Alzheimer's disease mouse models.Interestingly,both genetic and nanobody-based pharmacological blockage of tumor necrosis factor receptor 1 signaling was accompanied by favorable effects on Alzheimer's disease-associated inflammation,choroidal morphology and cognitive functioning.Here,we briefly summarize the detrimental effects that can be mediated by tumor necrosis factor/tumor necrosis factor receptor 1 signaling in(early) Alzheimer's disease,and the consequences this might have on the disease progression.As the main hypothesis in Alzheimer's disease clinical trials is still based on the amyloid beta-cascade,the importance of Alzheimer's disease-associated neuroinflammation urge the development of novel therapeutic strategies that might be effective in the early stages of Alzheimer's disease and prevent the irreversible neurodegeneration and resulting memory decline.展开更多
Meningioma in vivo research is hampered by the difficulty of establishing an easy and reproducible orthotopic model able to mimic the characteristics of a human meningioma. Moreover, leptomeningeal dissemination and h...Meningioma in vivo research is hampered by the difficulty of establishing an easy and reproducible orthotopic model able to mimic the characteristics of a human meningioma. Moreover, leptomeningeal dissemination and high mortality are often associated with such orthotopical models, making them useless for clinical translation studies. An optimized method for inducing meningiomas in nude mice at two different sites is described in this paper and the high reproducibility and low mortality of the models are demonstrated. Skull base meningiomas were induced in the auditory meatus and convexity meningiomas were induced on the brain surface of 23 and 24 nude mice, respectively. Both models led to the development of a mass easily observable by imaging methods. Dynamic contrast enhanced MRI was used as a tool to monitor and characterize the pathology onset and progression. At the end of the study, histology was performed to confirm the neoplastic origin of the diseased mass.展开更多
This paper provides an explicit representation of malignant cell division. To put this in perspective, the paper also provides a summary review of cellular division and duplication. Finally, a theory of tumor/cancer i...This paper provides an explicit representation of malignant cell division. To put this in perspective, the paper also provides a summary review of cellular division and duplication. Finally, a theory of tumor/cancer initiation following carcinogenic exposure is presented.展开更多
BACKGROUND Insufficient and contradictory data are available about the relation between directacting antivirals(DAAs)and hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV).AIM To analyze ...BACKGROUND Insufficient and contradictory data are available about the relation between directacting antivirals(DAAs)and hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV).AIM To analyze differences in basic clinical,radiological,and laboratory characteristics in addition to tumor behavior upon HCC diagnosis between patients with and without a previous history of DAAs exposure.METHODS This multicenter case-control study included 497 patients with chronic HCVrelated HCC,allocated into one of two groups according to their history of antiviral treatment for their HCV.RESULTS Group I included 151 HCC patients with a history of DAAs,while 346 patients who had never been treated with DAAs were assigned to group II.A significant difference was observed between both groups regarding basic assessment scores(Child,MELD,and BCLC),which tended to have more advanced liver disease and HCC stage upon diagnosis in group I.However,serum albumin was significantly affected,and serumα-fetoprotein was significantly higher in group II(P<0.001).In addition,group I showed significant HCC multicentricity than group II,while the incidence of portal vein thrombosis was significantly higher in group I(P<0.001).CONCLUSION The basic clinical scores and laboratory characteristics of HCC patients are advanced in patients who are naïve to DAAs treatment;however,HCC behavior is more aggressive in DAA-treated patients.展开更多
Cancer stem cells(CSC) are a rare cell population within a tumor characterized by the ability to form tumors following injection into an immunocompromised host. While the role of CSC has been clearly established in an...Cancer stem cells(CSC) are a rare cell population within a tumor characterized by the ability to form tumors following injection into an immunocompromised host. While the role of CSC has been clearly established in animal models, evidence of their clinical relevance has been harder to demonstrate. A number of markers, or combination thereof, have been used to detect and measure, although non-specifically, CSC in almost all human tumors. Several pathways have been identified as crucial for, but not necessarily unique to, CSC survivaland proliferation, and novel agents have been designed to target such pathways. A number of such agents have entered early phase development. Further, drugs that have long been marketed for non-oncological indications have been redirected to oncology as they appear to affect one or more of such pathways. This article aims to review the available evidence on the clinical relevance of CSC from a drug development standpoint and the results of early phase clinical trials of agents interfering with the above pathways. It also discusses limitations of current clinical trial design and endpoints to demonstrate antiCSC activity as well as possible strategies to overcome these limitations.展开更多
文摘BACKGROUND To evaluate the clinicopathological features and prognosis of gastric cancer(GC)occurring synchronously with gastrointestinal stromal tumor(GIST).CASE SUMMARY We report 19 patients with concurrent GC and GIST(17 male and 2 female,median age 62 years).GC was most often located in the lower third of the stomach.GIST was diagnosed preoperatively in four patients.GIST was most often located in the gastric body(n=8,42%).The most common growth pattern in GIST was extraluminal(n=12,63%).The positive expression rates of CD117 and CD34 in GIST were 100% and 95%,respectively.Most patients with GIST(n=17,89%)were very low or low risk.There was no recurrence of GIST during follow-up.The 3-year cumulative survival rate was 73.9%,and the 5-year cumulative survival rate was 59.2%.The combined analysis of this study and literature reports(47 reports,157 patients)found that GC and GIST were usually located in the lower third(42%)and middle third(51%)of the stomach.GC was usually early(stage I:42%),poorly differentiated(42%)intestinal-type adenocarcinoma(51%).GISTs were primarily small in diameter(median:1.2 cm)and very low or low risk(89%).CONCLUSION Synchronous GC and GIST may not be rare.They have specific clinicopathological characteristics,and may have mutual inhibition in pathogenesis and progression.
文摘BACKGROUND: Some scholars think that hypertension is the major risk factor to cause Binswanger disease (BD), however, BD is also found in some persons with normal blood pressure, so we presume that some other factors, such as diabetes mellitus, hyperlipemia, coronary heart disease and transient ischemic attacks and so on, might participant in the onset of BD. OBJECTIVE: To comparatively observe the difference in accompanying diseases, transcranial doppler (TCD) performance, blood glucose and blood lipid level between BD patients and healthy subjects who received health examination, and between BD patients with different disease condition. DESIGN: Case-control analysis. SETTING: Department of Emergency, Qingdao Municipal Hospital. PARTICIPANTS: Totally 126 patients with BD, 65 male and 61 female, aged from 67 to 85 years old, who hospitalized in the Medical School Hospital of Qingdao University and Qingdao Municipal People’s Hospital, were chosen, serving as BD patients group. All the patients met the clinical diagnostic criteria of BD introduced by Bennett et al. Another 126 persons, 65 male and 61 female, aged ranging from 67 to 80 years, who received health examination in the same hospital, were homeochronously chosen, serving as control group. Informed consents were obtained from all the subjects. METHODS: After being admitted, all the subjects including BD patients and persons who homeochronously received health examination in the same hospital were given examinations of blood pressure, blood lipid, blood glucose, electrocardiogram (ECG) and TCD. Fifty-seven patients with BD were in the stable period and 69 in the progressive period (Stable period: no local or subcortical function disorder found, and no changes in the range of white matter lesion showed by CT and/or MRI in recent 3 months; Progressive period: with local or subcortical function disorder and increase in the range of white matter lesion showed by CT and/or MRI in recent 3 months). According to intimal thickening of carotid artery and vertebral artery preformed by TCD, BD was graded as mild intimal thickening (< 1.1 mm), moderate intimal thickening (1.1 to 1.2 mm) and severe intimal thickening (> 1.2 mm). MAIN OUTCOME MEASURES: Comparison of the ratio of BD patients with accompanied diabetes mellitus, hyperlipemia, coronary heart disease and transient ischemic attacks, TCD performance, blood glucose and blood lipid level between BD patients group and control group, and among BD patients with various disease conditions. RESULTS: Totally 126 BD patients and 126 subjects who received health examination all participated in the result analysis. Intergroup comparison: ①The ratio of BD patients with accompanied hypertension, diabetes mellitus, hyperlipemia, transient ischemic attacks and coronary heart disease was 91.3%, 46.8%, 42.9%, 81.7% and 46.0% respectively in the BD patients group, and that was 36.5%, 17.5%, 15.9%, 34.1% and 34.1%, respectively in the control group. Significant difference existed between two groups (χ2=86.201,24.907,25.660,58.620,9.900, P < 0.01).②Compared with control group, anterior, middle cerebral and vertebrobasilar arteriosclerosis and insufficient cerebral blood supply existed significantly in BD patients with different disease condition(χ2=40.34,7.585,15.429, P < 0.01).③ Compared with control group, the level of blood glucose, total cholesterol and triglyceride of BD patients increased significantly (t=6.939,3.891,3.711,P < 0.01). Comparison among BD patients with different disease condition: ① Compared with stable period, transient ischemic attacks and coronary heart disease were found much in the BD patients at progressive period , with significant difference (χ2=7.196,13.517,P < 0.01).② Mild arteriosclerosis at stable period was found in 17 cases, and significant difference existed compared with progressive period (χ2=6.523,P < 0.05).③ There was no significant difference in the blood glucose and blood lipid level (t=1.755 6,0.583 1,0.824 6, P > 0.05). CONCLUSION: Hypertension, cerebral arteriosclerosis, diabetes mellitus, hyperlipemia, coronary heart disease and transient ischemic attacks have important effects on the onset of BD; Transient ischemic attacks and coronary heart disease can worsen the symptoms of BD patients.
文摘Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto
基金supported by the National Natural Science Foundation of China(Nos.51975400 and 62031022)Shanxi Provincial Key Medical Scientific Research Project(Nos.2020XM06 and 2021XM12)+3 种基金Fundamental Research Program of Shanxi Province(No.202103021224081)Shanxi Provincial Basic Research Project(Nos.202103021221006 and 202103021223040)Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2021L044)Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-TD026).
文摘Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells.The GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 model.Immunofluorescence analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the model.Compared with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and genes.Moreover,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three models.In addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude mice.Immunohistochemical evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was higher.This research therefore acts as a foundation for the application of 3DP-7721 models in drug development research.
基金funded by the projects initiated by the China Geological Survey(DD20221794 and DD20190414).
文摘Global energy structure is experiencing the third transition from fossil energy to non-fossil energy,to solve future energy problems,cope with climate change,and achieve net-zero emissions targets by 2050.Hydrogen is considered to be the most potential clean energy in this century under the background of carbon neutrality.At present,the industrial methods for producing hydrogen are mainly by steam-hydrocarbon(such as coal and natural gas)reforming and by electrolysis of water,while the exploration and development of natural hydrogen had just started.According to this literature review:(1)Natural hydrogen can be divided into three categories,including free hydrogen,hydrogen in inclusions and dissolved hydrogen;(2)natural hydrogen could be mainly from abiotic origins such as by deep-seated hydrogen generation,water-rock reaction or water radiolysis;(3)natural hydrogen is widely distributed and presents great potential,and the potential natural hydrogen sources excluding deep source of hydrogen is about(254±91)×10^(9) m^(3)/a according to a latest estimate;(4)at present,natural hydrogen has been mined in Mali,and the exploration and development of natural hydrogen has also been carried out in Australia,Brazil,the United States and some European countries,to find many favorable areas and test some technical methods for natural hydrogen exploration.Natural hydrogen is expected to be an important part of hydrogen energy production in the future energy pattern.Based on a thorough literature review,this study introduced the origin,classification,and global discovery of natural hydrogen,as well as summarized the current global status and discussed the possibility of natural hydrogen exploration and development,aiming to provide reference for the future natural hydrogen exploration and development.
基金supported by the National Natural Science Foundation of China (Nos.81472263 and 81201651)supported by the National Natural Science Foundation of China (No.81472264)+2 种基金a Grant from the Tianjin Municipal Science and Technology Commission (No.14JCYBJC27500)a Grant from the Tianjin Municipal Science and Technology Commission (No.13JCYBJC37400)the National Key Clinical Specialist Construction Programs of China (No.2013?544)
文摘Background: MicroRNA?506(miR?506) has been reported to function in several tumors as a tumor suppressor gene or oncogene. However, the expression and role of miR?506 in pancreatic ductal adenocarcinoma(PDAC) remains unclear. In this study, we aimed to evaluate the phenotype of miR?506 in PDAC.Methods: Using mi RNA in situ hybridization, we examined the expression of miR?506 in 113 PDACs and 87 paired normal pancreatic tissues. We evaluated mi R?506 expression in PDAC cells, normal pancreatic ducts, and acinus/islands, and we analyzed the associations between miR?506 expression and the clinicopathologic characteristics of PDAC patients.Results: miR?506 expression was higher in PDAC than in matched normal pancreatic ductal cells(P < 0.001). On the other hand, the combined group of well and moderately diferentiated PDACs showed higher levels of mi R?506 than the poorly diferentiated ones(P = 0.023). Moreover, mi R?506 expression was negatively associated with pathologic T category(P = 0.004) and lymph node metastasis(P = 0.033), suggesting that mi R?506 might inhibit the progression of PDAC.Conclusions: Our results suggest that mi R?506 either plays a role as an oncogene in the tumorigenesis and a tumor suppressor in the progression or serves as a house?keeping, tumor?suppressing mi RNA, whose expression can be activated by oncogenic signals in early development to hinder the progression of PDAC.
基金Supported by Shanghai Jiaotong University Medical School for Scientific Research,No.09XJ21013Shanghai Health Bureau for Scientific Research,No.2010029Shanghai Science and Technology Commission for Scientific Research,No.124119a0300
文摘AIM:To review the clinicopathological characteristics of concurrent gastrointestinal stromal tumors(GISTs) and gastric adenocarcinoma.METHODS:We retrospectively analyzed eight cases of synchronous adenocarcinoma and GIST in the stomach that had been surgically resected with curative intent between March 2003 and December 2008 in Xinhua hospital and Ruijin hospital.The adenocarcinoma was determined to be the primary tumor based on the histological features.The GIST cells were diffusely and strongly positive for CD34 and CD117.RESULTS:The patients were six men and two women aged 47-80 years(average,68.6 years).GIST was preoperatively detected in only one patient.The average sizes of the gastric adenocarcinomas and GISTs were 6.000 ± 2.6186 cm and 1.825 ± 1.4370 cm,respectively.All GISTs were very low-or low-risk lesions that were detected during evaluation,staging,operation or follow-up for gastric adenocarcinoma.CONCLUSION:We hypothesized that the stomach was influenced by the same unknown carcinogen,resulting in a simultaneous proliferation of different cell lines(epithelial and stromal cell).
基金Supported by National Natural Science Foundation of China,No.82272396Suzhou Medical and Health Science and Technology Innovation Project,No.SKY2022057The Youth Medical Talent of Jiangsu Province,No.QNRC2016475.
文摘Many digestive system malignant tumors are characterized by high incidence and mortality rate.Increasing evidence has revealed that the tumor microenvironment(TME)is involved in cancer initiation and tumor progression.Tumor-associated macrophages(TAMs)are a predominant constituent of the TME,and participate in the regulation of various biological behaviors and influence the prognosis of digestive system cancer.TAMs can be mainly classified into the antitumor M1 phenotype and protumor M2 phenotype.The latter especially are crucial drivers of tumor invasion,growth,angiogenesis,metastasis,immunosuppression,and resistance to therapy.TAMs are of importance in the occurrence,development,diagnosis,prognosis,and treatment of common digestive system malignant tumors.In this review,we summarize the role of TAMs in common digestive system malignant tumors,including esophageal,gastric,colorectal,pancreatic and liver cancers.How TAMs promote the development of tumors,and how they act as potential therapeutic targets and their clinical applications are also described.
文摘Abstract China used to have great urban rural disparity in socioeconomic development. Since the late 1980s, rapid socioeconomic development and urbanization have been taking place in rural settings. It is epidemiologically established that cancer scale and profile will transit as economy prospers and urbanization develops. However, there are few published studies reporting what changes are undergoing in cancer pattern in Chinese rural settings. Population-based tumor registration data collected by us in urban Shijiazhuang city (available for 2,374,827 people in 2012) and in rural Shexian County (available for 408,995 people since 2000) were used for urban rural comparison of age standardized incidence rate (ASIR) of westernization-related cancers in 2012, and the trend of biennial ASIR of these cancers for 2000-2015 in Shexian County was examined following a decade of rapid socioeconomic development and urbanization. From 1988-2015, the Gross Domestic Product per Capita (GDP) in rural Shexian County increased from 860 to 3000 US$, and urbanization rate from 22.4% to 54.8%. The biennial ASIRs of lung, colorectal, gallbladder cancer and leukemia in both sexes, and that of breast, ovary, thyroid, and kidney cancer in women increased significantly from 2000 - 2015. The increase from 2000-2001 to 2014-2015 in man and women for lung cancer was from 15.9 to 34.7 per 105 (P = 0.05) and 9.6 to 16.7 (P = 0.00), for colorectal cancer from 6.6 to 15.9 (P = 0.00) and 4.0 to 11.7 (P = 0.00), for gallbladder cancer from 0.1 to 2.4 (P = 0.00) and 0.3 to 2.7 (P = 0.00), for leukemia from 2.8 to 7.7 (P = 0.00) and 2.3 to 6.2 (P = 0.00);and in women for cancer of breast from 2.8 to 17.3 (P = 0.00), kidney from 0.2 to 2.4 (P = 0.00), ovary from 0.2 to 4.3 (P = 0.00), and thyroid from 0.2 to 4.2 (P = 0.00). Notwithstanding these increases, their ASIRs in 2012 in Shexian County were still significantly lower than that in Shijiazhuang city. Westernization-related cancer is increasing rapidly in rural China. Comprehensive measures are needed to strengthen prevention to ensure sustainable development.
文摘Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.
基金financial support from the National Natural Science Foundation of China(Nos.32171345,T2288101,U20A20390,and 11827803)Fok Ying Tung Education Foundation(No.141039)+1 种基金International Joint Research Center of Aerospace Biotechnology and Medical Engineering,Ministry of Science and Technology of China,the 111 Project(No.B13003)the Academic Excellence Foundation of BUAA for PhD Students.
文摘Postoperative adhesion(POA)widely occurs in soft tissues and usually leads to chronic pain,dysfunction of adjacent organs and some acute complications,seriously reducing patients’quality of life and even being life-threatening.Except for adhesiolysis,there are few effective methods to release existing adhesion.However,it requires a second operation and inpatient care and usually triggers recurrent adhesion in a great incidence.Hence,preventing POA formation has been regarded as the most effective clinical strategy.Biomaterials have attracted great attention in preventing POA because they can act as both barriers and drug carriers.Nevertheless,even though much reported research has been demonstrated their efficacy on POA inhibition to a certain extent,thoroughly preventing POA formation is still challenging.Meanwhile,most biomaterials for POA prevention were designed based on limited experiences,not a solid theoretical basis,showing blindness.Hence,we aimed to provide guidance for designing anti-adhesion materials applied in different soft tissues based on the mechanisms of POA occurrence and development.We first classified the postoperative adhesions into four categories according to the different components of diverse adhesion tissues,and named them as“membranous adhesion”,“vascular adhesion”,“adhesive adhesion”and“scarred adhesion”,respectively.Then,the process of the occurrence and development of POA were analyzed,and the main influencing factors in different stages were clarified.Further,we proposed seven strategies for POA prevention by using biomaterials according to these influencing factors.Meanwhile,the relevant practices were summarized according to the corresponding strategies and the future perspectives were analyzed.
基金Supported by the Capital Health research and Development of Special fund,No.2014-3-4014
文摘Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors(GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and m RNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin(PI3K/AKT/m TOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/m TOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/m TOR pathway and the development of GISTs.
文摘Objective: To study the value of gastroenterultrasound developer in diagnosis of the stomach tumor. Methods: 38 patients who diagnosed as stomach tumor by gastroscopy were chosen, and their images before and after by using gastroenterultrasound developer were compared. Results: The difference between the detectable rate of stomach tumor before and after by using gastroenterultrasound developer was significant (P < 0.01). Conclusion: Gastroenterultrasound developer has a high diagnostic value in diagnosis of the stomach tumor.
基金supported by the Research Foundation Flanders(FWO)The Foundation for Alzheimer’s Research Belgium(SAO-FRA)+1 种基金European Union Cost action MouseAge(BM1402)the Baillet Latour Fund(all to SS and REV)
文摘Due to the aging of the population and despite the enormous scientific effort,Alzheimer's disease remains one of the biggest medical and pharmaceutical challenges in current medicine.Novel insights highlight the importance of neuroinflammation as an undeniable player in the onset and progression of Alzheimer's disease.Tumor necrosis factor is a master inflammatory cytokine that signals via tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2,but that also regulates several brain functions in health and disease.However,clinical trials investigating drugs that interfere with the tumor necrosis factor pathway in Alzheimer's disease led to inconclusive results,partially because not only the pro-inflammatory tumor necrosis factor/tumor necrosis factor receptor 1,but also the beneficial tumor necrosis factor/tumor necrosis factor receptor 2 signaling was antagonized in these trials.We recently found that tumor necrosis factor is the main upregulated cytokine in the choroid plexus of Alzheimer's disease patients,signaling via tumor necrosis factor receptor 1.In agreement with this,choroidal tumor necrosis factor/tumor necrosis factor receptor 1 signaling was also upregulated in different Alzheimer's disease mouse models.Interestingly,both genetic and nanobody-based pharmacological blockage of tumor necrosis factor receptor 1 signaling was accompanied by favorable effects on Alzheimer's disease-associated inflammation,choroidal morphology and cognitive functioning.Here,we briefly summarize the detrimental effects that can be mediated by tumor necrosis factor/tumor necrosis factor receptor 1 signaling in(early) Alzheimer's disease,and the consequences this might have on the disease progression.As the main hypothesis in Alzheimer's disease clinical trials is still based on the amyloid beta-cascade,the importance of Alzheimer's disease-associated neuroinflammation urge the development of novel therapeutic strategies that might be effective in the early stages of Alzheimer's disease and prevent the irreversible neurodegeneration and resulting memory decline.
文摘Meningioma in vivo research is hampered by the difficulty of establishing an easy and reproducible orthotopic model able to mimic the characteristics of a human meningioma. Moreover, leptomeningeal dissemination and high mortality are often associated with such orthotopical models, making them useless for clinical translation studies. An optimized method for inducing meningiomas in nude mice at two different sites is described in this paper and the high reproducibility and low mortality of the models are demonstrated. Skull base meningiomas were induced in the auditory meatus and convexity meningiomas were induced on the brain surface of 23 and 24 nude mice, respectively. Both models led to the development of a mass easily observable by imaging methods. Dynamic contrast enhanced MRI was used as a tool to monitor and characterize the pathology onset and progression. At the end of the study, histology was performed to confirm the neoplastic origin of the diseased mass.
文摘This paper provides an explicit representation of malignant cell division. To put this in perspective, the paper also provides a summary review of cellular division and duplication. Finally, a theory of tumor/cancer initiation following carcinogenic exposure is presented.
文摘BACKGROUND Insufficient and contradictory data are available about the relation between directacting antivirals(DAAs)and hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV).AIM To analyze differences in basic clinical,radiological,and laboratory characteristics in addition to tumor behavior upon HCC diagnosis between patients with and without a previous history of DAAs exposure.METHODS This multicenter case-control study included 497 patients with chronic HCVrelated HCC,allocated into one of two groups according to their history of antiviral treatment for their HCV.RESULTS Group I included 151 HCC patients with a history of DAAs,while 346 patients who had never been treated with DAAs were assigned to group II.A significant difference was observed between both groups regarding basic assessment scores(Child,MELD,and BCLC),which tended to have more advanced liver disease and HCC stage upon diagnosis in group I.However,serum albumin was significantly affected,and serumα-fetoprotein was significantly higher in group II(P<0.001).In addition,group I showed significant HCC multicentricity than group II,while the incidence of portal vein thrombosis was significantly higher in group I(P<0.001).CONCLUSION The basic clinical scores and laboratory characteristics of HCC patients are advanced in patients who are naïve to DAAs treatment;however,HCC behavior is more aggressive in DAA-treated patients.
文摘Cancer stem cells(CSC) are a rare cell population within a tumor characterized by the ability to form tumors following injection into an immunocompromised host. While the role of CSC has been clearly established in animal models, evidence of their clinical relevance has been harder to demonstrate. A number of markers, or combination thereof, have been used to detect and measure, although non-specifically, CSC in almost all human tumors. Several pathways have been identified as crucial for, but not necessarily unique to, CSC survivaland proliferation, and novel agents have been designed to target such pathways. A number of such agents have entered early phase development. Further, drugs that have long been marketed for non-oncological indications have been redirected to oncology as they appear to affect one or more of such pathways. This article aims to review the available evidence on the clinical relevance of CSC from a drug development standpoint and the results of early phase clinical trials of agents interfering with the above pathways. It also discusses limitations of current clinical trial design and endpoints to demonstrate antiCSC activity as well as possible strategies to overcome these limitations.
