Animals ; Diestrus ; drug effects ; Female ; Hyperprolactinemia ; physiopathology ; Panax ; Prolactin ; blood ; Rats ; Rats, Wistar ; Saponins ; pharmacology

Objective To evaluate the clinical significance of CK20 mRNA expression in the blood of gastric cancer patients. Methods Expression of CK20 mRNA was detected by FQ-PCR in preoperative peripheral blood, tumour drainage blood and postoperative peripheral blood in 55 gastric patients and 60 blood donors.Results There was no positive expression of CK20 mRNA of peripheral blood in 60 healthy blood donors.The expression rate of CK20 mRNA was 45.45% in preoperative peripheral blood.The expression rate was higher in stage Ⅲ Ⅳ than stage ⅠⅡ patients ( P

Purpose To study the malignant transformation after treating rat oval cell line ( WB-F344 ) with chemical carcinogen N-methyl-N′-nitro-N-nitrosoguanidine ( MNNG) . Methods WB-F344 cells were cultured with MNNG for severe times. The biological characteristics of induced cells were detected through the following methods:to check proliferation activity by flow cytometry analysis, to examine malignant transformation degree of induced cells by soft agar assay and tumor formation in NOD/SCID mice, and to investi-gate the transcriptional and protein levels of hepatocellular carcinoma marker GGT, GST-P by real time-PCR. Results Oval cells in-duced by MNNG showed changes in biological characteristics and malignant molecular markers. Conclusion Hepatic oval cells model is successfully established, which can be confirmed by tumor formation in NOD/SCID mice.

Objective To discuss The Clinical Significance of Eosinophil (EOS) in urosepsis. Methods A total of 99 patients of urosepsis in Department of Urology,Guangdong Provincial TCM Hospital from Mar. 2013 to Jul. 2016 were selected as research objects by retrospective analysis. The patients were classified into groupEOS= 0 andgroup EOS > 0,group PCT(procalcitonin)≥ 2 ng/mL andgroup PCT < 2 ng/mL,the differences of PCT concentration and percentage of EOS in two groups were analyzed comparatively. 99 patients of urosepsiswere also compared the difference of the percentage of EOS with another group including 100 patients of urinary tract infection (UTI) without Sepsis. Results The percentage of EOS was significantly decreased in 86.9%(86/99)of patients of urosepsis. The paired student t test show the percentage of EOS in two days after treatment,four days after treatment, before hospital discharge were higher than that before the treatment, the difference wassignificant (P < 0.05). The Independent-Sample Test show that the PCTconcentration in EOS = 0 group were higher than EOS > 0 group,the percentage of EOS in PCT≥2 ng/mL groupwere lower than PCT<2 ng/mL group,difference were significant(P<0.05). And The Independent-Sample Testalso showed that the percentage of EOS of the Urosepsis group was definitely lower than the UTI group without Sepsis. Difference was statistically significant. Concusions The percentage of EOS could be applied to assess the severity of urosepsis, monitor the disease progression and evaluate the infection control. The cost was lower than PCT in therapeuticprocess ofurosepsis.

Objective To analyze the prognostic factors and their influences on breast cancer patients with local-regional recurrence.Methods From Jan.1st,1998 to Dec.30th,2007,66 breast cancer patients with local-regional recurrence were treated at Breast Center of Peking University People's Hospital.The overall survival of the patients was analyzed using Kaplan Meier survival analysis and the prognostic factors such as primary tumor status,initial treatment,location of recurrence and treatment strategy after local recurrence were analyzed using Cox regression model.Results The median follow-up was 111 months.The median survival for the 66 patients with recurrence was 99 months,ranging from 3 to 188 months and 5-year survival rate was 60％.Kaplan-Meier analysis revealed statistically significant better survival for patients with unifocal primary tumor,undergoing initial breast conservation surgery,with local recurrence only and undergoing radical local treatment after local recurrence (P =0.003,P =0.017,P =0.050,and P =0.000 respectively).COX regression analysis showed that age at initial diagnosis and radical local treatment after recurrence had influences on post-recurrence survival of patients without distant metastasis (P =O.004 and 0.000 respectively).Conclusion The clinical and pathological features of primary tumor,initial surgery,site of recurrence and treatment strategy after recurrence have influences on prognosis of breast cancer patients with local-regional recurrence.

With high selectivity and potency, target protein degradation technology has recently emerged as a strategy for drug discovery and design. Proteolysis-targeting chimeras (PROTAC) function as inducers for the degradation of target proteins and are a research focus in drug development. Current research on PROTAC mainly revolves around the rational design of PROTAC molecules, the discovery of new E3 ubiquitin ligase ligands and improvement in drug targeting. In this review, we focus on the PROTAC linker and its effects on the generation of the E3 enzyme-PROTAC-target protein ternary complex from three standpoints: length, binding site and chemical properties. We discuss the influences of the linker on the efficacy and the selectivity of PROTAC molecules.

OBJECTIVETo investigate the accumulation of advanced glycation end products (AGE) and the inflammatory response of skin and wound in diabetic patients, and to analyze their relationship in vitro.

METHODSHistological staining and immunohistochemical staining was respectively performed on skin and wound tissue specimens collected from 10 patients with Type II diabetes mellitus (diabetes group) and 12 non-diabetic patients with skin injury (control group) to observe the arrangement of collagen and the distribution of inflammatory cells, and to determine the expression levels of AGE and its receptor (RAGE). Malondialdehyde (MDA) levels in skin and wound tissue homogenates were assayed by enzyme-linked immunosorbent assay. In vitro, human neutrophils were isolated and treated with RPMI-1640 culture medium or that containing AGE-human serum albumin in the concentration of 0.315, 0.625, 1.250 mg/mL, and they were identified as normal control (NC) group, low concentration (L) group, moderate concentration (M) group, and high concentration (H) group. Cell viability in each group was determined by MTT colorimetric assay, and the reactive oxygen species (ROS) in cell was measured with 2', 7'-dichlorofluorescein-diacetate. Data were processed with t test.

RESULTSCompared with those of skin in control group, collagens of skin tissues in diabetes group atrophied and disorderly arranged. Inflammatory cells in wounds in diabetes group were dispersed, in which collagens arranged loosely and irregularly, as compared with those of wounds in control group. Expression levels of AGE and RAGE of skin in diabetes group were higher than those in control group. In diabetes and control groups, especially in diabetes group, the numbers of RAGE-positive cells in wound tissue were more than those in skin tissue. Large amount of inflammatory cells with positive expression of RAGE were observed in diabetes group. MDA level of skin and wound tissue in diabetes group was respectively (6.3 ± 1.0), (7.1 ± 2.4) nmol per milligram protein, which were obviously higher than those in control group [(2.9 ± 1.0), (3.6 ± 1.4) nmol per milligram protein, with t value respectively 8.017, 4.349, P < 0.05 or P < 0.01]. Cell viability and ROS levels in neutrophils were increased in L, M, and H groups [(59 ± 8)%, (77 ± 5)%, (67 ± 6)% and 1.67 ± 0.14, 2.13 ± 0.17, 3.48 ± 0.48] as compared with those in NC group [(34 ± 5)% and 0.58 ± 0.06, with t value respectively 7.195, 14.890, 11.130 and 20.195, 24.905, 16.864, P < 0.05 or P < 0.01].

CONCLUSIONSAbnormal oxidative stress in diabetic skin leads to an atypical origin of wound repair. AGE-RAGE effect is a critical mediator for oxidative stress in diabetic wound tissue during wound healing.

Aged ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; metabolism ; pathology ; Female ; Glycation End Products, Advanced ; metabolism ; Humans ; Male ; Middle Aged ; Oxidative Stress ; Reactive Oxygen Species ; metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism ; Serum Albumin ; metabolism ; Serum Albumin, Human ; Skin ; metabolism ; pathology ; Wound Healing

OBJECTIVETo investigate the therapeutic efficacy of interferon (IFN) therapy and risk of long-term administration for chronic hepatitis C (CHC) patients who cannot tolerate the standard treatment.

METHODSForty-six CHC patients who had proven intolerant to standard treatments were treated with low-dose IFN (non-pegylated IFN: 60 to 300MIU QOD, or pegylated IFN: 50 to 90 mug/w) plus ribavirin (RBV; 0.6g to 0.9 g/d) for 72 weeks.

RESULTSForty-three (93.5%) of the patients were able to tolerate the long-term treatment with low-dose IFN plus RBV. Only three patients experienced severe side effects (low white blood cell and platelet counts) that required treatment withdrawal. The virology response rates over treatment time were: rapid virologic response (RVR): 10.9%; early virus response (EVR): 30.4%; 24 week virologic response: 45.7%; and, 48 week virologic response: 47.8%. B-sonographic imaging revealed that three patients experienced improved liver morphology through the treatment course. The patients who achieved RVR, EVR, or 24 weeks virologic response also attained higher 48 week virologic response. The 24 week virologic response had the strongest predictive value of good prognosis.

CONCLUSIONSOur study demonstrated that long-term treatment with low-dose interferon plus ribavirin is effective for patients who are otherwise intolerant to standard treatment. In these patients, low-dose IFN plus RBV can obtain a high virologic response rate at 48 week. Furthermore, the 24 week virologic response is sufficiently predictive of treatment success. As with any treatment regimen, it is important for healthcare workers to monitor the disease status and potential side effects throughout the course of therapy.

Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; Female ; Hepacivirus ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferons ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVETo explore the influence of verbal working memory load on associative neural networks.

METHODSTwenty-one subjects were required to complete a verbal delayed matching-to-sample task under the condition of low (3 items) or high (5 items) working memory load (WML). The 19-channels event-related potentials (ERP) were analyzed with statistical parametric mapping.

RESULTSA significant difference in working memory capacity (WMC) was found between low WML and high WML groups [2.48∓0.30 vs 3.30∓0.76; t(20)=5.950, P=0.000]. Statistical parametric mapping revealed that during the encoding stage, the effects of WML appeared in succession in the right ventral attention network (rVAN), the dorsal attention network, and the language areas in the left hemisprere. During the maintenance stage, the effects WML occured in the rVAN acompanied by either DAN or left frontal-temporal regions. CONCLUSIONS;onclusions When the WML is beyond the WMC, the rVAN may participate in the prevention of interference among items and in the activation of long-term memory.

Attention ; Evoked Potentials ; Frontal Lobe ; physiology ; Humans ; Memory, Short-Term ; Spatio-Temporal Analysis

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests