Objective:To systematically evaluate the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) plus surgery versus neoadjuvant chemotherapy (NCT) plus surgery in the treatment of advanced esophageal squamous cell carcinoma.Methods:Clinical controlled trials of comparing the treatment of NCRT plus surgery with NCT plus surgery for esophageal squamous cell carcinoma were electronically searched from the databases including PubMed, The Cochrane Library, EMbase, CBM, CNKI, WanFang and VIP from the inception of databases to January, 2019. Two reviewers independently screened the literatures, extracted data and assessed the risk of bias of the included studies. And then, a meta-analysis was performed by using RevMan 5.3 software.Results:A total of 8 clinical control studies were included, including 995 patients with esophageal squamous cell carcinoma. Meta-analysis results showed that compared with the NCT group, the R 0 resection rate was significantly higher ( OR=2.14, 95% CI: 1.03-4.45, P=0.040) and the pathological complete response (pCR) rate was significantly higher ( OR=4.19, 95% CI: 1.71-10.28, P=0.002) in the NCRT group. The incidence of postoperative complications ( OR=1.37, 95% CI: 0.76-2.48, P=0.300) and the risk of perioperative death ( OR=1.28, 95% CI: 0.58-2.83, P=0.54) were not significantly different between two groups. The long-term survival of patients with esophageal squamous cell carcinoma in the NCRT group was significantly better compared with that in the NCT group ( HR=0.77, 95% CI: 0.64-0.92, P=0.005). Conclusions:Compared with NCT plus surgery for advanced esophageal squamous cell carcinoma, NCRT plus surgery has higher R 0 resection rate and pCR rate, does not significantly increase the risk of perioperative complications or perioperative death, and significantly improves the long-term survival of esophageal squamous cell carcinoma patients.

Animals ; Cisplatin ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; drug effects ; metabolism ; Male ; Proteinuria ; etiology ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVESTo investigate the relationship between the quantity of peripheral dendritic cell (DC) and of serum HBV DNA and the inflammatory level in chronic hepatitis B (CHB).

METHODSThe myeloid DC (DC1) and plasmacytoid DC (DC2) in fresh peripheral blood were enumerated by using three-color flow cytometry in chronic hepatitis B patients and healthy donors. The hepatic inflammatory levels were evaluated by percutaneous liver biopsy. The serum HBV DNA levels were determined by real-time PCR.

RESULTSCHB patients with serum HBV DNA < or = 10(6) copies/ml exhibited a significant increase in the percentage of circulating DC2 in comparison with those of CHB patients with serum HBV DNA > or = 10(6) and with healthy donors (P < 0.05). The two latter groups showed no significant differences between each other. There was also no significant difference in the relative quantity of peripheral blood DC1 among the three groups mentioned above (P = 0.162). No evidence was found to support that the relative quantity of peripheral blood DC2 was associated with the clinical severity of the disease or the inflammatory level in the liver (P > 0.05).

CONCLUSIONThe relative quantity of peripheral blood DC2 is associated with HBV DNA level. It is suggested that DC2 may play a pivotal role in inhibiting HBV replication in CHB patients. There was no relationship found between relative quantities of DCs and the inflammatory level in the liver.

DNA, Viral ; blood ; Dendritic Cells ; cytology ; immunology ; Female ; Hepatitis B virus ; physiology ; Hepatitis B, Chronic ; immunology ; pathology ; virology ; Humans ; Liver ; pathology ; Male ; Virus Replication

Adult ; Female ; Humans ; Influenza A Virus, H5N1 Subtype ; physiology ; Influenza, Human ; diagnostic imaging ; virology ; Male ; Radiography

OBJECTIVETo investigate the expression of manganese superoxide dismutase (MnSOD) and to determine the relationship between MnSOD expression and clinicopathological features, biological behaviors in esophageal carcinoma.

METHODSImmunohistochemistry (SP) and RT-PCR were respectively used to detect the expression of MnSOD in 45 specimens of esophageal carcinoma tissues and normal esophageal mucosa (5 cm distant from the margin of cancer).

RESULTSThe positive rate of MnSOD protein expression was 31.1% in esophageal carcinoma tissues, significantly lower than 86.7% in the normal tissues (P < 0.05). The expressions of MnSOD mRNA and protein were significantly correlated with the lesion length, depths of invasion and histological grade (P < 0.05), but not with lymph node metastasis, lesion site and gross type of the tumor (P > 0.05). The relative content of MnSOD mRNA was (0.310 ± 0.036) and (0.482 ± 0.053) in the cancer and normal tissues, respectively, with a significant difference between the two groups (P < 0.05). The relative content of MnSOD mRNA was significantly related to lesion length, depths of invasion and histological grade (P < 0.05), but not correlated with lymph node status, lesion site and gross type of the tumor (P > 0.05).

CONCLUSIONThe expression of MnSOD protein and mRNA is decreased in esophageal carcinoma, suggesting that MnSOD gene may be closely associated with the carcinogenesis and the degree of malignancy. Detection of MnSOD expression may be useful in diagnosis, treatment and prognosis of esophageal carcinoma.

Adult ; Aged ; Carcinoma, Squamous Cell ; enzymology ; pathology ; Esophageal Neoplasms ; enzymology ; pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Superoxide Dismutase ; genetics ; metabolism

Cardiac troponin T (cTnT) serves as a structural protein of myocardial fiber, and participates in heart excitation-contraction coupling process. Here, we generated tnnt2a (cTnT-coding gene) deletion mutant zebrafish via CRISPR/Cas9 technique, and performed phenotypic analysis of the identified tnnt2a mutants. We observed that there was no significant difference between heterozygous mutant and wild type zebrafish, and the homozygous mutants displayed significant malformations in heart, including cardiac arrest, atrium and ventricle enlargement, pericardium effusion, and the individuals usually died before 7 day post fertilization (dpf). We further analyzed the expression alternations of heart sarcomere genes (tnnt2a, actc1a, tpm4a, myl7, vmhc) at transcriptional level in tnnt2a(Δ2) zebrafish by performing real time RT-PCR, and found that the RNA expression level of tnnt2a in tnnt2azebrafish decreased constantly at each time point of developmental stages, and actc1a, tpm4a, myl7 and vmhc all showed higher expressions at early developmental stages and lower expressions at late developmental stages, in comparison with those of wild type zebrafish. Lastly, electron microscopy on cardiac tissues suggested that there were significant changes of the thick or thin filament structures in tnnt2a(Δ2) zebrafish, which was further confirmed by F-actin and Tpm4 immunofluorescence staining. The tnnt2azebrafish generated by CRISPR/Cas9 bears the most common symptoms of patients with dilated cardiomyopathy, and therefore can be used as a tool to study TNNT2-deficiency related cardiomyopathy.
Animals ; CRISPR-Cas Systems ; Disease Models, Animal ; Gene Knockout Techniques ; Myocardium ; pathology ; Sequence Deletion ; Troponin T ; genetics ; Zebrafish ; Zebrafish Proteins ; genetics

BACKGROUNDA five-year follow-up study of intensive multifactorial intervention was undertaken to assess the changes of circulating serum amyloid A (SAA) levels and the incidence of atherosclerosis (AS) in patients with short-duration type 2 diabetes mellitus (T2DM) without macroangiopathy, and whether intensive multifactorial intervention could prevent or at least postpone the occurrence of macroangiopathy.

METHODSAmong 150 patients with short-duration T2DM, 75 were assigned to receive conventional outpatient treatment (conventional group) and the others underwent intensive multifactorial integrated therapy targeting hyperglycemia, hypertension, dyslipidemia and received aspirin simultaneously (intensive group).

RESULTSPlasma SAA levels were higher in diabetic patients than those in healthy control subjects, and decreased obviously after intensive multifactorial intervention. The levels of SAA were positively correlated with body mass index (BMI), waist hip ratio (WHR), triglyceride (TG), high sensitive C-reactive protein (hs-CRP) and common carotid intima-media thickness (CC-IMT). The standard-reaching rates of glycemia, blood pressure and lipidemia were significantly higher in intensive group than those of conventional group. The incidence of macroangiopathy decreased by 58.96% in intensive group compared with conventional group.

CONCLUSIONSIntensive multifactorial intervention may significantly reduce the SAA levels and prevent the occurrence of AS in short-duration patients with T2DM. SAA might be one of the risk factors of T2DM combined with AS.

Adult ; Aged ; Antihypertensive Agents ; pharmacology ; therapeutic use ; Blood Glucose ; metabolism ; C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; metabolism ; Diabetic Angiopathies ; etiology ; Female ; Humans ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Hypolipidemic Agents ; pharmacology ; therapeutic use ; Male ; Middle Aged ; Multivariate Analysis ; Serum Amyloid A Protein ; metabolism ; Triglycerides ; blood ; Tunica Media ; drug effects

Background A five-year follow-up study of intensive multifactorial intervention was undertaken to assess the changes of circulating serum amyloid A(SAA)levels and the incidence of atherosclerosis(AS)in patients with short-duration type 2 diabetes mellitus(T2DM)without maoroangiopathy,and whether intensive multifactorial intervention could prevent or at least postpone the occurence of macroangiopathy.Methods Among 150 patients with short-duration T2DM,75 were assigned to receive conventional outpatient treatment (conventional group)and the others underwent intensive multifactorial integrated therapy targeting hyperglycemia,hypertension,dyslipidemia and received aspirin simultaneously(intensive group).Results Plasma SAA levels were higher in diabetic patients than those in healthy control subjects,and decreased obviously after intensive multifactorial intervention.The levels of SAA were positively correlated with body mass index(BMI),waist hip ratio(WHR),triglyceride(TG),high sensitive C-reactive protein(hs-CRP)and common carotid intima-media thickness(CC-IMT).The standard-reaching rates of glycemia,blood pressure and lipidemia were significantly higher in intensive group than those of conventional group.The incidence of macroangiopathy decreased by 58.96% in intensive group compared with conventional group.Conclusions Intensive multifactorial intervention may significantly reduce the SAA levels and prevent the occurrence of AS in short-duration patients with T2DM.SAA might be one of the risk factors of T2DM combined with AS.

Objective:From a new perspective，to explore therapeutic effect of Huidouba (HDB) on alleviating kidney oxidative damage in rats with diabetic nephropathy (DN) and provide a scientific basis for developing HDB as a potential Tibetan medicine for treatment of DN. Method:Rats were fed with high-fat diet (HFD) and injected with streptozocin (STZ, 65 mg·kg^-1) intraperitoneally to induce DN model, while rats in Blank group were injected with an equal volume of vehicle and fed with normal chow. The successfully modeling DN rats were randomly divided into three groups, 8 rats per group, DN model group (10 mL·kg^-1·d^-1), Metformin group (0.045 g·kg^-1·d^-1) and HDB group (0.18 g·kg^-1·d^-1). Monitor body weight (BW) and fasting blood glucose (FBG) weekly, and collect 24 hours urine before and after medication to examine microalbuminuria (mAlb). Calculate kidney index (KI) after sacrificing, analyze mAlb, serum creatinine (SCr) and blood urea nitrogen (BUN) with a fully automatic biochemical analyzer. Histopathology of kidney was observed by Masson staining. Lipid peroxidation malondialdehyde (MDA) assay kit was used to examine MDA content in kidney tissue. Nox4, as a subtype of triphosphopyridine nucleotide (NADPH) oxidase family was determined by Western blot and immunofluorescence assay of kidney tissue. Result:Compared with blank group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in DN model group were increased (P<0.01), tissue damage was obvious and Nox4 expression in glumeruli was increased significantly (P<0.01). Compared with DN model group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in drug administration groups were decreased (P<0.01), kidney injury was alleviated and Nox4 expression was down-regulated（P<0.01）. Conclusion:HDB as a Yiqiyangyin Tibetan medicine, could ease oxidative stress injury of kidney and reduce proteinuria in DN rats, thus prevent the development of DN. Its mechanism is closely related to down-regulating Nox4 expression of kidney tissue in DN rats.