Objective To investigate the clinical significance of DNA haploid analysis for malignant degree and prognosis assessment of breast carcinoma. Methods Highclarity Colourful Pathological Analysis System-1000( HPIAS-1000) was used to analyze the DNA haploid of 120 breast carcinoma patients who had been followed up for more than 5 years. All patients were divided into three groups according to histology. 48 advanced differentiation cases, 44 middle differentiation cases and 28 low differentiation cases. Then DNA haploid analysis was made,that is diploid(2C) ,3 - 4C,aneuploid(AN). Results Except for 3 -4C,there were significant differences betweenⅠandⅡgrade ,ⅡandⅢgrade,ⅠandⅢgrade( P

Molecular target-based cancer therapy is playing a more and more important role in cancer therapy because of its high specificity, good tolerance and so on. There are different kinds of molecular targeted drugs such as monoclonal antibodies and small molecular kinase inhibitors, and more than 50 drugs have been approved since 1997. When the first monoclonal antibody, rituximab, was on the market. The development of molecular target-based cancer therapeutics has become the main approach. Based on this, we summarized the drugs approved by FDA and introduced their mechanism of actions and clinical applications. In order to incorporate most molecular targeted drugs and describe clearly various characteristics, we divided them into four categories: drugs related to EGFR, drugs related to antiangiogenesis, drugs related to specific antigen and other targeted drugs. The purpose of this review is to provide a current status of this field and discover the main problems in the molecular targeted therapy.
Angiogenesis Inhibitors ; Antibodies, Monoclonal ; Drug Delivery Systems ; Humans ; Molecular Targeted Therapy ; Neoplasms ; drug therapy ; Protein Kinase Inhibitors ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors

Objective To estimate the biological effects of leptin on human HaCaT keratinocytes and explore their molecular mechanisms.Methods Cell counting kit-8 (CCK-8) was used to evaluate the proliferation of cultured HaCaT cells treated with different concentrations of leptin for 24 and 48 hours.Some HaCaT cells were classified into four groups to remain untreated,be treated with leptin (100 μg/L) and piceatannol (a specific inhibitor of STAT3 phosphorylation) alone or in combination for 24 hours,respectively,followed by the evaluation of cell proliferation using CCK-8 kit.Flow cytometry was performed to assess cell cycle of HaCaT cells treated with leptin of 100 μg/L,Western blot to determine the phosphorylation level of Erk1/2 and STAT3 in HaCaT cells treated with leptin of 100 μg/L for different durations.Statistical analysis was done by Student's t-test for unpaired data using GraphPad Prism 5 software.Results The proliferation of HaCaT cells was accelerated to different degrees after treatment with leptin of 50 and 100 μg/L for 24 and 48 hours,and the accelerating effect was in a dose-dependent manner within 24 hours (r =0.9989,P ＜ 0.05).Piceatannol apparently inhibited the promotive effect of leptin on the proliferation of HaCaT cells.There was an obvious elevation in the percentage of cells at S phase ((57.70 ± 5.88)％ vs.(42.50 ± 7.55)％,P ＞ 0.05),but a significant decrease in that at G0/G1 phase ((39.70 ± 1.57)％ vs.(45.20 ± 1.44)％,P ＜ 0.05),with a significant increase in proliferation index (0.603 ±0.0157 vs.0.564 ± 0.0144,P ＜ 0.05) in HaCaT cells treated with leptin of 100 μg/L for 24 hours compared with the untreated controls.Western blot showed that leptin of 100 μg/L markedly enhanced the phosphorylation level of STAT3 in HaCaT cells.Conclusion Leptin may upregulate the proliferation of HaCaT cells through activation of STAT3 pathway.

Objective To investigate the efficacy of acupuncture and rehabilitation therapy on lower limb motor function, and to explore a cortical mechanism using functional near infrared spectroscopy (fNIRS). Methods From December, 2020 to July, 2021, 24 stroke patients with lower limb motor dysfunction in our hospital were randomly divided into rehabilitation group (n = 12) and acupuncture-rehabilitation group (n = 12), and received routine rehabilitation training and acupuncture-rehabilitation intervention for four weeks, respectively. The control group included ten healthy subjects matched the patients. Before and after intervention, the lower limb motor function of the patients was assessed with Fugl-Meyer Assessment-Lower Extremities (FMA-LE), and all the subjects accepted fNIRS examination. The functional intensity and lateralization index (LI) of supplementary motor area (SMA), premotor cortex (PMC) and sensory motor cortex (SMC) were calculated based on oxygenated hemoglobin (HbO2). Results There was no significant difference in FMA-LE score between the rehabilitation group and the acupuncture-rehabilitation group before the intervention (P > 0.05). After four weeks of intervention, FMA-LE scores improved in both groups (t > 3.770, P < 0.001), and improved more in the acupuncture-rehabilitation group than in the rehabilitation group (t = 2.252, P < 0.05). Before intervention, the average functional connection was more intensitive in the control group than in the two patients groups (P < 0.05), and there was no significant difference between the later two groups (t = 0.458, P > 0.05). After intervention, the average functional connection increased in both groups (t > 2.178, P < 0.05), and the functional connection of the affected PMC of acupuncture-rehabilitation group increased (P < 0.05). The LI in SMC increased in the acupuncture-rehabilitation group (P < 0.05). There was a significant positive correlation between the change of functional connection of the affected PMC and the change of FMA-LE scores in the acupuncture-rehabilitation group (r = 0.579, P < 0.05). Conclusion Acupuncture with rehabilitation therapy can significantly improve the lower limb motor function and asymmetrical activation of SMC in stroke patients. The recovery of lower limb motor function may be related to the enhanced activation of affected PMC.

Purpose:To study the activity of toremifene and its synergistic effect with anti-tumor drugs on human lung adenocarcinoma cell line A549,which might be expected to provide a new mode of therapy for the clinical management of lung cancer.Methods:The cytotoxic effects of these agents on human lung cancer cell line A549 were measured by a tet- razolium-based volorimetric assay (MTT assay).Results:Toremifene can inhibit the growth of A549 cell directly.The A value of the low dose toremifene combined with anti-tumor drugs were lower than that of anti-tumor drugs alone.Toremifene combined with VCR,ADM,DDP and VP-16 showed better effects.Conclusions:Toremifene combined with chemotherapy drugs shows significant synergistic anti-tumor effect on A549 cell.This might provide experimental evidence for lung cancer therapy.

Compared with normal tissues and cells, the tumor microenvironment has significant differences. For example, glutathione-related metabolic enzymes and reactive oxygen species are highly expressed in different subcellular structures, resulting in an unbalanced redox state. Aiming at the specific redox state in tumor tissues and cells, a series of small molecule prodrug self-assembled nanoparticles can be designed and connected by intelligent response linkers including disulfide bonds, sulfide bonds, and selenium bonds, thioketal bonds, etc. The in vitro and in vivo efficiency and metabolic mode of these nanoparticles are related to the type of linker. This review will summarize the tumor redox microenvironment, the design of intelligent responsive small molecule prodrug nanoparticles, and the metabolic pathways of small molecule prodrug nanoparticles with different connecting linkers and their relationship with drug efficacy.

AIMTo investigate the absorption and distribution of recombinant hirudin-2 (rHV2) in the GI tract in rats after oral administration.

METHODSUsing HPLC, fluorescence spectrophotometry and confocal laser scanning microscopy to measure the amount of intact rHV2 absorbed into gastrointestinal mucosa and blood.

RESULTSHPLC spectrum showed that there were intact rHV2 molecules in plasma after 1 h of oral administration. After oral administration for 3 h, 1.2%-26.8% of fluorescence was found in the GI tract in rats. Chromatographic analysis showed that 2.27%-38.75% of fluorescence recovered from the GI tract luminal contents and mucosa was eluted at the void volume of a Sephadex G-25 column. Microscopic examination showed that FITC-rHV2 was taken up throughout the whole small intestine but the ileum appeared to be a preferred site for FITC-rHV2 transport in rats.

CONCLUSIONrHV2 may partially survive in the GI lumen and subsequently absorbed in active form by gastrointestinal tract.

Administration, Oral ; Animals ; Digestive System ; metabolism ; Fibrinolytic Agents ; administration & dosage ; pharmacokinetics ; Fluorescein-5-isothiocyanate ; Hirudins ; administration & dosage ; pharmacokinetics ; Ileum ; metabolism ; ultrastructure ; Intestinal Absorption ; Intestinal Mucosa ; metabolism ; ultrastructure ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; administration & dosage ; pharmacokinetics ; Tissue Distribution

To systematically evaluate the efficacy and safety of tripterygium glycosides (TG) combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV. The computer retrievals were made in Cochrane Libarary, PubMed, Embase, SCI, Sinnomed, CNKI, Chinainfo and VIP, and hand retrievals were conducted for meeting and academic papers (updated to December 30, 2014), in order to collect randomized controlled trials and quasi-randomized control trials for TG combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV and set the literature inclusion and elimination standards. Eligible literatures were included and evaluated according to standards in Cochrane Handbook. RevMan 5.3 and Stata 12.0 were used for a Meta-analysis. A total of 13 randomized controlled trials and quasi-randomized control trials involving 1119 patients with diabetic nephropathy were included. The Meta analysis result showed that compared with the control group, the combination group showed better effects in reducing the 24-hour urinary protein [MD = -0.84, 95% CI (-1.02, -0.66)], raising albumin [SMD = 0.98, 95% CI (0.81, 1.16)], the total efficiency [OR = 4.23, 95% CI (2.77, 6.46)] and the significant efficiency [OR = 5.35, 95% CI (2.70, 10.60)], with no statistical difference in Serum Creatinine between Both groups [MD = -0.82, 95% CI (-4.30, 2.66), P = 0.64]. However, the risk of adverse reactions increased by 7% [RD = 0.07, 95% CI (0.03, 0.12)]. The Egger's test showed no publication bias. Tripterygium Glycosides combined with ACEI/ARB in treating diabetic nephropathy stage IV is supper than the single administration of ACEI/ARB, with a good prospect in clinical application. Nevertheless, due to the small-size and low-quality samples in this study, more high-quality and large sample-size randomized controlled trials shall be conducted to verify the findings.
Angiotensin Receptor Antagonists ; administration & dosage ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; Diabetic Nephropathies ; drug therapy ; Drug Therapy, Combination ; Glycosides ; administration & dosage ; Humans ; Tripterygium ; chemistry

Under indoors simulating natural growing condition, the 4th-instar Mythimna separata larvae were fed by using poi- son leaf disk method. The effect of total ginsenosides on the protective enzymes (PPO, T-SOD, CAT and POD) of M. separata larvae was studied. The total ginsenosides could influence the protective enzymes of 4th-instar M. separata larvae significantly. After treated by total ginsenosides, the PPO activities increased firstly then decreased, and tended to equilibrium, and reached the maximum after 48 h. Furthermore, the total ginsenosides disturbed the dynamic balance of SOD, CAT and POD of M. separata larvae, and the yield of O2-* speeded. The results suggest that the total ginsenosides influence the protective enzymes of 4th-instar M. separata larvae, and disturb the original dynamic balance of protective enzymes. Consequently the insect suffers from the harm of O2-*.
Animals ; Enzymes ; metabolism ; Ginsenosides ; metabolism ; Larva ; metabolism ; Lepidoptera ; metabolism ; Oxygen ; metabolism

Objective To explore the treatment methods and prognostic factors of metachronous liver metastases from gastric cancer.Methods The clinicopathological data of 102 patients with metachronous liver metastases from gastric cancer who were admitted to the Cancer Hospital of Tianjin Medical University from January 1996 to December 2008 were retrospectively analyzed.Sixty-four patients received systemic chemotherapy,19 received systemic chemotherapy + transcatheter arterial chemoembolization (TACE),and 19 received systemic chemotherapy + radical resection of the metachronous liver cancer.Patients were re-examined every 3 months within the first 3 years after operation,and every 6 months after postoperative year 3,and every 1 year after postoperative year 5.Physical examination,laboratory test and imaging examination were done during the follow-up.The followup was ended in October 2013.The cumulative survival rates of the patients were calculated and compared using the Kaplan-Meier method and the Log-rank test,respectively.The prognostic factors were analyzed using the COX regression model.Results The disease was alleviated in 15 patients,progressed in 27 patients,and the condition was stable in 22 patients after systemic chemotherapy.The disease was alleviated in 6 patients,progressed in 4 patients and the condition was stable in 9 patients after systemic chemotherapy + TACE.Of the 19 patients received systemic chemotherapy + radical resection of the metachronous liver cancer,1 was complicated with incisional infection,and no patient died perioperatively.Sixteen patients died of gastric cancer recurrence including 10 patients with local recurrence and 6 patients with multiple lesions recurrence.Eight patients missed the follow-up,the others were followed up for 9-149 months.The overall median survival time was 8 months (range,2-70 months),and the 1-,3-,5-year survival rates were 40.2％,17.7％ and 6.8％,respectively.The median survival time of the 64 patients who received systemic chemotherapy was 5 months (range,2-37 months),and the 1-,3-,5-year survival rates were 15.6％,3.5％ and 0,respectively.The median survival time of the 19 patients who received systemic chemotherapy +TACE was 6 months (range,3-36 months),and the 1-,3-,5-year survival rates were 26.1％,6.5％ and 0,respectively.The median survival time of the 19 patients who received systemic chemotherapy + radical resection of the metachronous liver cancer was 15 months (range,5-70 months),and the 1-,3-,5-year survival rates were 63.2％,31.6％ and 16.8％,respectively.The prognosis of patients who received systemic chemotherapy + radical resection of the metachronous liver cancer was superior to those who received systemic chemotherapy or systemic chemotherapy + TACE (x2=23.900,P ＜ 0.05).The results of univariate analysis showed that diameter and differentiation of primary tumor,extra-hepatic metastasis,type and number of liver metastases and treatment regimen were correlated with the prognosis of patients with metachronous liver metastases from gastric cancer (x2=6.307,7.908,4.375,45.188,18.234,23.900,P ＜ 0.05).The results of multivariate analysis showed that type and number of liver metastases were independent factors influencing the prognosis of patients with metachronous liver metastases from gastric cancer (OR=5.217,3.292,95％CI:1.428-2.882,1.054-2.514,P＜0.05).Conclusions Surgical resection of the metachronous liver cancer is important to improve the survival of patients.The type and number of liver metastases are important factors in deciding the treatment methods.