Objective:To investigate the effect of early protein supplementation on the clinical outcomes of elderly ICU patients with critically ill.Methods:The study was a post-hoc analysis of a multicenter, cluster randomized controlled trial (NEED trial), which aimed to evaluate the impact of feeding protocol on nutritional implementation and outcomes in ICU patients. It was planned to include elderly patients aged ≥70 years from the NEED trial, and patients who had not started nutritional therapy by the Day 3 after enrolment, stayed in the ICU less than 7 days, missing the primary outcome were excluded. The primary outcome of this study was 28-day mortality of enrolment. Patients were categorized into Q1 (<0.6 g/kg/d), Q2 (0.6-0.83 g/kg/d), and Q3 (≥0.83 g/kg/d) groups according to the tertiles of protein supply. The log-rank test was used to compare the Kaplan-Meier survival curves for 28-day mortality. The associations between different protein groups and 28-day mortality were tested by Cox proportional hazards regression models. Subgroup analysis was conducted in patients with high (mNUTRIC score≥5) nutritional risk or patients with baseline acute kidney injury.Results:A total of 789 elderly (≥70 years) patients was included in the study, with a mean protein amount of 0.69 (0.53, 0.91) g/(kg·d) during days 3-7 after ICU admission, and mean protein amounts in the Q1 low-protein group, the Q2 medium-protein group, and the Q3 high-protein group were 0.46 (0.36, 0.53), 0.69 (0.63, 0.76), and 1.03 (0.91, 1.23) g/(kg·d), respectively. The results showed that the medium protein group associated with lower 28-day mortality compared to the high protein group, and the association between the medium protein group and lower 28-day mortality still held after controlling for possible confounders by Cox multivariate regression analysis. In the high-nutritional risk subgroup (mNUTRIC≥5), a significant association was also found between the medium protein group and lower 28-day mortality.Conclusions:Early high protein supply are not beneficial for elderly ICU patients by this large sample size post-hoc analysis, and medium protein supply associate with lower 28-day mortality compared with the high protein group. This study may provide a theoretical basis for the optimal dose of early protein supply in elderly ICU patients, as well as a reference for clinical implementation.

Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.
Epigenetic Repression ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant/genetics* ; Receptors, Androgen/genetics* ; Transcriptional Activation

To investigate the anti-pyretic and anti-endotoxin effect of Chinese herb medicine Jinhuaqingre capsules.Thirty healthy male New Zealand rabbits with lipopolysaccharide-induced fever were divided into 5 groups (6 rabbits in each): animals in model group were given normal saline by gavage, animals in positive control group were given aspirin (0.2 g/kg), and animals in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0 or 1.5 g/kg, respectively. The changes in body temperature of rabbits were observed. Fifty healthy Kunming mice were divided into 5 groups (10 mice in each): mice in model group were given normal saline by gavage, mice in positive control group were given aspirin (0.2 g/kg), and those in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0, 1.5 g/kg, respectively. Matrix coloration method was used to detect the degradation rate of endotoxin in mice.The body temperature in rabbits of high and medium dose Jinhuaqingre capsule groups declined significantly 60 min after drug administration, and the temperature of high-dose group returned to the baseline after 300 min; while the body temperature of low-dose group started to decline at 180 min after drug administration. The endotoxin degradation rates in mice of high, medium and low dose groups was (56.73±3.12)%, (47.23±1.77)% and (21.08±2.30)% at 30 min after drug administration; those were (82.76±1.00)%, (64.75±1.77)% and (38.21±1.57)% at 60 min after drug administration, respectively.Chinese herb medicine Jinhuanigre capsules have anti-pyretic and anti-endotoxin effects, which may provide a new option for the treatment of heat-toxin syndrome.
Animals ; Antitoxins ; pharmacology ; Aspirin ; therapeutic use ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; Fever ; chemically induced ; drug therapy ; Lipopolysaccharides ; antagonists & inhibitors ; Male ; Medicine, Chinese Traditional ; Mice ; Rabbits ; Sodium Chloride ; therapeutic use

Objective To study the anti-inflammatory,antitussive,and analgesia effects of Jinhua qingre capsules.Methods The anti-inflammatory effect was assessed by the methods include xylene-induced mouse auricular swelling and histamine-induced pigment oozing from skin vessel in rats;The antitussive and analgesic effect were assessed by ammonia water induced cough model and acetic acid-induced twisting method.Results In anti-inflammation experiment,the high dose (12 g·kg-1) and moderate (6 g·kg-1) groups of Jinhua qingre capsules showed significant inhibitory effect on auricular swelling and significant difference compared with control group (P ＜ 0.01,P ＜ 0.05.);the high dose (10 g· kg-1) and moderate dose (5 g·kg-1) groups of Jinhua Qingre capsules play a marked inhibitory role in the increase in mouse peritoneal capillary permeability (P ＜ 0.01,P ＜ 0.05).In antitussive experiment,high dose (12 g· kg-1) and moderate dose (6 g· kg-1) groups had significant inhibitory effect on cough caused by ammonia water (P ＜ 0.01,P ＜ 0.05) compared with control group.In analgesic experiment,the high dose (12 g·kg-1),moderate dose (6 g·kg-1),and low dose (3 g·kg-1) groups effectively reduced the writhing frequency of mice (P ＜ 0.01,P ＜ 0.05).Conclusion Jinhua qingre capsules have potential effects on anti-inflammatory,antitussive,and analgesic.

Objective To investigate effects of preoperative application of parecoxib on postoperative analgesia and coagulation function in neurosurgical patients.Methods A total of 90 patients (38 males and 52 females,ASA physical status Ⅰ or Ⅱ) undergoing crainotomy were randomly divided into two groups(n=45): parecoxib group (group P) and control group (group C).At 30 min before operation,group P received intravenous injection of parecoxib 40 mg (5 ml),group C intravenous injection of saline 5 ml.Postoperative patient-controlled intravenous analgesia (PCIA) was performed in all patients.PCIA formula of sufentanil 2 μg/kg+tropisetron 0.2 mg/kg,were diluted with normal saline to 120 ml.The visual analogue scale (VAS),the total and effective PCIA pump compressions,Ramsay sedation scale of 2,4,16,24,48 h after operation were recorded.Coagulation function was measured before and 2 h,48 h after parecoxib administration.Meanwhile,adverse reactions were recorded.Results Comparion of VAS between the two groups was made within 48 h after surgery,the total and effective PCIA pump compressions,were much more in group C than in group P (P<0.05).Ramsay sedation scale of group C was higher than that in group P at 2 h after operation.There were no significant differences in coagulation function.And the percentage of patients′ adverse effects in group P was lower than that in group C (P<0.05).Conclusion Parecoxib,as an analgesic,can enhance analgesic effect of sufentanil PCIA.Not only does it reduce the amount of sufentanil and incidence of adverse reactions,but also it has no significant effect on blood coagulation function.

To verify the reliability of targeted detecting HER2 positive cancer cells and clinical pathological tissue specimens with a recombinant anti HER2 single chain antibody in single chain Fv fragment (scFv) format, we have constructed the fusion variable regions of the ScFv specific for HER2/neu. labeled a green-fluorescent protein(GFP). The humanized recombinant Anti HER2 ScFv-GFP gene was inserted into pFast Bac HT A, and expressed in insect cells sf9. Then the recombinant fusion protein Anti HER2 ScFv-GFP was properly purified with Ni2+-NTA affinity chromatography from the infected sf9 cells used to test the specificity of the fusion antibody for HER2 positive cancer cells. Firstly, the purified antibody incubated with HER2 positive breast cancer cells SKBR3, BT474 and HER2 negative breast cancer cells MCF7 for 12 h/24 h/48 h at 37 degrees C, in order to confirm targeted detecting HER2 positive breast cancer cells by Laser Confocal Microscopy. Furthermore, the same clinical pathological tissue samples were assessed by immunohistochemistry (IHC) and the fusion antibody Anti HER2 ScFv-GFP in the meanwhile. The data obtained indicated that the recombinant eukaryotic expression plasmid pFast Bac HT A/Anti HER2 ScFv-GFP was constructed successfully In addition, obvious green fluorescent was observed in insect cells sf9. When the purified fusion antibody was incubated with different cancer cells, much more green fluorescent was observed on the surface of the HER2 positive cancer cells SKBR3 and BT474. In contrast, no green fluorescent on the surface of the HER2 negative cancer cells MCF7 was detected. The concentration of the purified fusion antibody was 115.5 microg/mL, of which protein relative molecular weight was 60 kDa. The analysis showed the purity was about 97% and the titer was about 1:64. The detection results of IHC and fusion antibody testing indicated the conformity. In summary, the study showed that the new fusion antibody Anti HER2 ScFv-GFP can test HER2 positive cancer cells, indicating a potential candidate method for clinical HER2 positive specimens detection.
Animals ; Breast Neoplasms ; diagnosis ; pathology ; Female ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; Humans ; MCF-7 Cells ; Receptor, ErbB-2 ; analysis ; Recombinant Fusion Proteins ; genetics ; Sf9 Cells ; Single-Chain Antibodies ; genetics

Objective: To study relative risk factors for diabetic nephropathy (DN). Methods: A total of 238 patients diagnosed as type 2 diabetes mellitus (DM) were enrolled in the study. According to urine microalbuminuria to urine creatinine ratio (UACR), patients were divided into pure DM group (group DM1, n=90), early diabetic nephropathy group (group DM2 , n=73) and clinical diabetic nephropathy group (group DM3 ,n=75). Clinic data of all patients were collected; Fasting blood glucose (FBG), 2h postprandial blood glucose (2hPB), blood lipids, uric acid (UA), fibrinogen (Fg) and glycosylated haemoglobin (HbA1c) were measured in all patients, and their correlations with DN were analyzed. Results: Compared with group DM1, the course of disease in DM [(7.25±6.29) years vs. (10.25±7.67) years vs. (13.53±7.82) years], levels of FBG [(8.46±2.52) mmol/L vs. (9.52±3.38) mmol/L vs. (10.82±3.30) mmol/L], 2hPB [(18.40±5.64) mmol/L vs. (20.27±5.94) mmol/L vs. (22.59±6.14) mmol/L], HbA1c [(7.96±1.65) % vs. (8.60±1.76) % vs. (9.55±2.09) %], triglyceride [TG, (1.72±0.86) mmol/L vs. (2.34±1.87) mmol/L vs. (3.16±1.85) mmol/L], Fg [(3.49±0.93) g/L vs. (3.88±1.21) g/L vs. (4.99±2.10) g/L] and UA [(295.42±52.34) μmol/L vs. (324.18±96.29) μmol/L vs. (351.23±56.88) μmol/L] significantly increased in group DM2 and group DM3 in order (P<0.01~0.001). Logistic gradual regression analysis indicated that course of DM, HbA1c, TG, Fg and UA were risk factors for DN (OR=1.008~1.910, P<0.01~0.001). Conclusion: The course of DM, blood glucose, blood lipid, uric acid and fibrinogen are risk factors of diabetic nephropathy; increased UACR reflects progress of patient’ condition in DM patients, its detection is used for diabetic prognosis and treatment.

Objective To compare the efficacy of insulin aspart and human soluble insulin on postprandial glucose control and blood glucose excursion in type 2 diabetic patients managed with insulin pump therapy. Methods All of 345 hospitalized type 2 diabetic patients were randomized divided into two groups. One group underwent insulin pump therapy with insulin aspart (aspart group, 173 cases),another group with human soluble insulin (humulin R group, 172 cases). Capillary glucose concentrations were measured at 9 time points,including preprandial,2 hours postprandial,bedtime (22:00),midnight(0:00) and 3:00 every day during the treatment. The change of blood glucose at each time point and the variation of postprandial blood glucose excursion was compared between the two groups. The frequency of hypoglycemia was also evaluated. Results After treatment, fasting blood glucose and post breakfast and post dinner blood glucose levels were decreased more significantly in the aspart group than those in the humulin R group. And a significantly smaller postprandial blood glucose excursion was shown in the aspart group compared with that in the humulin R group (P< 0.05). The time to achieve good glycemic control in the aspart group was (4.40 ± 2.16) d, significantly shorter than that in the humulin R group[(5.68 ± 2.29) d](P< 0.05). The incidence of hypoglycemia was significantly lower in the aspart group (P <0.05). Conclusion Insulin aspart results in better control of blood glucose and less glycemic variability compare with human soluble insulin in type 2 diabetic patients during delivery by continuous subcutaneous insulin infusion.

cuses tumors. Survivin seems to be a promising marker for analyzing clinical stages and predicting the prognosis of TCC.

Objective To observe the therapeutic effect of glycosaminoglycans(GAGs)on diabetes mellitus with early nephropathy in order to find a new therapeutic approach to diabetic nephropathy. Methods 60 cases of type 2 diabetic nephropathy(albuminuria:30 to 300mg/24h,male/female:38/22,ages:43-70 years old, course of disease:1-30 years)without hypertension were selected. Some indexes were analyzed before and after administration of regular therapy in routine group or glycosaminoglycans group. The elderly group and non elderly group of diabetes nephropathy were compared. When the metabolism is stable, the levels of endothelin (ET), Netricoxide (NO)and urinary albumin excretion rate(UAER)were measured. Results After three months treatment, the levels of UAER were decreased significantly in both GAGs group and routine group(P＜0.01).After three months, UAER was decreased step by step, and there was no difference between the two groups. The levels of UAER had no change in regular group and there was significant difference between this group and the other two groups. In GAGs group, the levels of whole blood viscosity of medium shear rate 1,whole blood viscosity of medium sheer rate 2,whole blood viscosity of low shear rate were declined and serum NO increased significantly; that of plasma viscosity, whole blood reduced viscosity, ET were all decreased to some degree. Conclusion GAGs has the therapeutic effect on type 2 diabetic nephropathy patients with microalbuminuria because of decreasing UAER and reversing the development of DN. The benefit was positively correlated with the time of taking glycosaminoglycans.