The potential of herbal drugs to treat heart failure:The roles of Sirt1/AMPK

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

Analysis of Lymph Node Metastases of 1,526 Cases with Thoracic Esophageal and Cardiac Carcinomas: A Random Sampling Report froni the Fourth Hospital of Hebei Medical University from 1996 to 2004

OBJECTIVE To summarize the regular pattern and state oflymph node metastasis of patients with esophageal and cardiaccarcinomas,so as to analyze factors influencing lymph nodemetastasis.METHODS Clinical data collected from 1,526 thoracicesophageal and cardiac carcinoma patients who were admitted inthe Fourth Hospital of Hebei Medical University during a periodfrom January 1996 to December 2004,were randomly selectedand an Access Database of the patient's information was set up.Eight clinico-pathologic factors,including the patient's age,tumorlocation and size,pathological classification,the depth of tumorinvasion,vascular tumor embolus (VTE),the state of surroundingorgan encroachment and the status of tumor residues,wereidentified.A correlation between these factors and metastases wasstatistically analyzed using SPSS13.0 software.RESULTS Lymph node metastatic sites from esophagealcarcinomas included the thoracic and abdominal cavity.Lymphnode metastasis from the superior esophageal carcinomasmainly occurred in the neck and thoracic cavity.There was atwo-way lymph node metastasis in the patients with the middleesophageal carcinoma.The inferior esophageal carcinomas mainlymetastasized to the paraesophageal,paragastric cardia,and leftgastric artery lymph nodes.The rate and degree of the metastasisfrom the inferior esophageal carcinomas were significantly highercompared to those of the superior and the middle esophagealcarcinomas (P<0.0125).The degree of abdominal lymph node metastasis fromcarcinomas of the gastric cardia was significantly higher comparedwith that of esophageal carcinomas.In the group with carcinomaof the gastric cardia,the rate and degree of the lymph nodemetastases in the paragastric cardia and left gastric artery weresignificantly higher compared to the group with esophagealcarcinoma (P<0.05).Paraesophageal lymph node metastasis fromcarcinomas of the gastric cardia in the thoracic cavity frequentlyoccurred,too,and the degree of the metastasis was similar to thatof esophageal carcinoma.There was no significant difference inthe rate and degree of the paraesophageal lymph-node metastasisbetween the group with carcinoma of the gastric cardia comparedto those with esophageal carcinoma (P>0.05).Multifactoriallogistic regression analysis showed that the tumor size,depth oftumor encroachment,VTE,and tumor residues could all bringabout obvious impact on lymph-node metastases (P<0.05).CONCLUSION Lymph node metastasis from superioresophageal carcinomas mainly occurs in the neck and thoraciccavity.The middle esophageal carcinomas presented a two-waylymph-node metastasis (both the upwards and the downwards),and the lymph node metastasis from inferior esophagealcarcinomas mainly occurred in the thoracic and abdominal cavities.The metastases of carcinoma of the gastriccardia were most commonly found in the abdominalcavity,with frequent paraesophageal lymph-nodemetastasis.The sufficient attention should be paidto neck lymph node clearance in cases of esophagealcarcinoma.What is of the greatest concern is theclearance of the left gastric artery lymph nodes,andalso in cases of gastric cardia carcinoma,clearance,the paraesophageal lymph nodes.With an increasein the tumor size and depth of tumor encroachment,and occurrence of VTE and tumor residual cells,therisk of lymph node metastasis is significantly raised (P<0.05).

Analysis of Prognostic Factors of Esophageal and Gastric Cardiac Carcinoma Patients after Radical Surgery Using Cox Proportional Hazard Model-A Random Sampling Study from the Fourth Hospital of Hebei Medical University during the Period of 1996-2004

OBJECTIVE To retrospectively analyze clinical data of patientsfrom our hospital who underwent radical surgery for esophagealcarcinoma and for adenocarcinoma of the gastric cardia,as well asto investigate prognostic factors affecting the long-term survival ofthe patients.METHODS Data from the patients eligible for our study,admitted to the 4th Hospital of Hebei Medical University fromJanuary 1996 to December 2004,were randomized,and 12distinctive clinicopathologic factors influencing the survival rateof those who underwent radical surgery for esophageal carcinomaor carcinoma of the gastric cardia were collected.Univariate andmultivariate analysis of these individual variables were performedusing the Cox proportional hazard model.RESULTS It was shown by univariate analysis that age,tumorsize,pathologic type,lymph node status,TNM staging,depthof infiltration and encroachment into local organs,etc.,were thefactors that markedly influenced the prognosis of patients(P<0.01).Multivariate analysis showed that pathologic type,numberof the lymph node metastases,involvement of local organs,andTNM staging were independent prognostic factors(P<0.05).CONCLUSION The independent factors influencing theprognosis of patients with esophageal cancer and carcinoma ofthe gastric cardia include pathologic type,number of lymph nodemetastases,involvement of local organs and TNM staging.Themain prognostic factors affecting the patient's survival are patientage,tumor size and depth of infiltration.In addition,patients withinvolvement of the local organs have a worse prognosis,and theyshould be closely followed up.

Clinical Analysis of 15 Patients with Adult-Type Pulmonary Blastoma

OBJECTIVE To study the clinical and histopathological characteristics of pulmonary blastoma(PB),and to review the diagnostic criterion and treatment methods.METHODS Clinical and histopathological data from 15 cases of PB in this hospital,from 1990 to 2006,were retrospectively analyzed.RESULTS Surgical procedures were conducted in all 15 patients,including pulmonary lobectomy in 9,lobectomy of the 2 right pulmonary lobes in 2,excision of pulmonary segments in 1,lobectomy and bronchoplasty in 1,lobectomy and angioplasty in 1,and excision of the whole left lung in 1.Of the 15 cases,11 were misdiagnosed as lung cancer,2 were doubted to be a benign tumor before surgery,1 was suspected to be a malignant mesenchymoma,and only 1 was diagnosed as a PB.CONCLUSION Preoperative final diagnosis of PB is very difficult,since the clinical symptoms of the disease are nonspecific.To confirm the diagnosis,comprehensive consideration of the factors,such as the clinical manifestations,morphological characteristics and immunohistochemical tumor markers,should be taken.Surgery is the treatment of choice for PB,and a thorough removal is the key to a cure.PB has a high malignancy and o en recurs and metastasizes,usually with a poor prognosis.

Analysis of Clinicopathologic Features of Esophageal Carcinoma Patients Undergoing Surgery-a Report of 4,329 Cases

OBJECTIVE To investigate the clinicopathological features of esophageal carcinoma （EC） patients, and to analyze epidemiologic characteristics and the current situation of esophageal cancioma in the southern area of Hebei Province. METHODS A total of 4329 patients with esophageal cancinoma, undergoing surgery in the Fourth Hospital of Hebei Medical University during a period from January 1996 to December 2005, were selected. Collection and statistical analysis of the pathologic data were performed using a SAS 6.0 software package. RESULTS Over the past ten years, there has been a tendency for an increase in the mean age of EC onset （P 〈 0.05）, a downtrend in the percentage of squamous cancer （SqCa） （P 〈 0.05） and an uptrend in the frequency of small cell carcinoma （P 〈 0.05）. In clinical stages, there was a drop in the percentage of Stage-Ⅱ squamous EC patients （P 〈 0.05）, and an increase in that of Stage-Ⅳ patients （P 〈 0.05）. There were statistical differences in sex, age, pathologic types, depth of infiltration, ratio of stages and lymph node metastasis, etc. among the superior, middle and inferior segments of the EC diseased region （P 〈 0.05）. CONCLUSION It was relatively late for the EC patients from this area to see a doctor, resulting in a drop in the ratio of SqCa and an ascensus in that of small cell cancer. However, due to a low incidence of adenocarcinoma, no obvious ascending tendency was found in the frequency of this carcinoma over the past ten years.

Tumor-homing peptide-based NIR-II probes for targeted spontaneous breast tumor imaging

Fluorescence imaging in the second near-infrared window(NIR-Ⅱ,1000-1700 nm)is a promising modality for real-time imaging of cancer and image-guided surgery with superior in vivo optical properties.So far,very few NIR-Ⅱfluorophores have been reported for in vivo biomedical imaging of chemically-induced spontaneous breast carcinoma.Herein,a NIR-Ⅱfluorescent probe CH1055-F3 with the nucleolin-targeted tumor-homing peptide F3 was demonstrated to prefe rentially accumulate in 4 T1 tumors.More importantly,CH1055-F3 exhibited specific NIR-Ⅱsignals with high spatial and temporal resolution,strong tumor uptake,and remarkable NIR-Ⅱimage-guided surgery in dimethylbenzanthracene(DMBA)-induced spontaneous breast tumor rats.This report presents the first tumor-homing peptide-based NIR-Ⅱprobe to diagnose transplantable and spontaneous breast tumors by the active targeting.

Small-Molecule Fluorophores for Near-Infrared IIb Imaging and ImageGuided Therapy of Vascular Diseases

Accurate and dynamic visualization of vascular diseases can contribute to restraining further deterioration from diseases in a timely manner.However,visualization is still unable to precisely determine whether and to what extent blood vessels or brain tissues are damaged.Here,we report novel benzobis(1,2,5-thiadiazole)-based second near-infrared region(NIR-II)fluorophores HY1-HY4 with highly twisted structures(55°at the S_(0) state),extremely strong aggregation-induced emission(AIE)characteristics(I/I_(0)>13),and remarkably high fluorescence quantum yields(QYs)(up to 14.45%)in the NIR-II region(>1000 nm)and∼0.27%in the nearinfrared IIb window(NIR-IIb,>1500 nm)in aqueous solution.Using NIR-IIb AIE HY4 dots,high-resolution NIR-IIb fluorescence imaging of revascularization and thrombolysis,and real-time feedback of the therapeutic efficacy of Chinese medicine Dengzhan Xixin injection(DXI)on ischemic stroke,were achieved for the first time.In addition,results showed that DXI conferred neuroprotection against cerebral ischemia injury mediated via the angiogenesis pathway.These attractive results provide a new perspective for designing ultrabright NIR-IIb probes for vascular-related phenomena,disease assessment,and precise intraoperative imageguided therapy with a deeper tissue penetration depth and higher resolution.

A novel small-molecule near-infrared II fluorescence probe for orthotopic osteosarcoma imaging

Osteosarcoma is the most common primary malignant tumor of bone,particularly among children and adolescents.Advances in imaging,surgical techniques,and implants have dramatically reduced the need for amputation in the past three decades.Recently,in vivo fluorescence imaging in the second near-infrared window(NIR-II,1,000–1,700 nm)shows impressive advantages of deeper tissue penetration and higher spatial resolution,which makes it a promising tool for the early diagnosis and post-operative observation of Osteosarcoma.To the best of our knowledge,this paper is the first time to develop a novel NIR-II fluorescence probe conjugated with an osteosarcoma targeted oligopeptide for molecular tumor imaging in a xenograft orthotopic osteosarcoma mouse model.