Prognostic impact of pERK in advanced hepatocellular carcinoma patients treated with sorafenib.

BACKGROUND: Sorafenib represents the standard of care targeted therapy for patients with advanced hepatocellular carcinoma (HCC). However, biomolecules that predict a patient's response to sorafenib treatment for HCC remain largely unknown. Thus, this study was designed to investigate whether phosphorylated ERK (pERK) and members of the sorafenib target or PI3K/Akt/mTOR signaling pathway predict the efficacy of sorafenib in advanced HCC patients. METHODOLOGY: From December 2008 to October 2011, pathological specimens from 54 advanced HCC patients received sorafenib treatment were obtained. Clinicopathological variables, treatment response, survival and time to progression (TTP) were recorded. Immunophenotypical analysis was carried out using antibodies against pERK, phosphorylated S6K (pS6K), VEGFR2 and PTEN. RESULTS: The median overall survival (OS) and TTP were 14.2 and 3.4 months, respectively, and the disease control rate (DCR) was 59.3%. Better Eastern Cooperative Oncology Group Performance Status (ECOG PS) (95% CI: 3.27-4.93 m vs. 1.15-2.85 m, p = 0.01), Child-Pugh class A score (95% CI: 3.47-4.53 vs. 1.14-2.06 m, p < 0.01), and higher pERK (3.34-6.66 m vs. 1.33-2.67 m, p = 0.03) and VEGFR2 (3.49-6.52 m vs. 2.15-2.73 m, p = 0.04) immunohistochemical staining score were associated with increased TTP by univariate analysis. The ECOG PS (p = 0.022), Child-Pugh class (p = 0.045) and pERK staining score (p = 0.012) were found to be associated with TTP using multivariate analysis. CONCLUSION: Sorafenib treatment outcome is favorable in advanced HCC patients who received tumor resection and who have a good ECOG PS and Child-Pugh class A liver function. The pERK immunohistological staining score, ECOG PS and Child-Pugh class may be helpful in determining patients most likely to benefit from sorafenib therapy.

Advances in the development of functional foods from buckwheat.

Buckwheat originated in North or East Asia and is widely adapted in North America. It has been grown since at least 1000 BC in China. It has very strong adaptability to adverse environments with a very short growing span. Many varieties are growing around the world, but mainly in the north hemisphere. Currently the most common buckwheat spice is Fagopyrum esculentum Moench (common buckwheat or sweet buckwheat), while Fagopyrum tartaricum is also available in some mountainous regions. Many nutraceutical compounds exist in buckwheat seeds and other tissues. Buckwheat has been used and will be better used as an important raw material for functional food production. In this review we focus on works related to the development of functional foods from common buckwheat, Fagopyrum esculentum Moench. A lot of research has be conducted in the functionalities and properties of buckwheat proteins, flavonoids, flavones, phytosterols, thiamin-binding proteins, and other rare compounds in buckwheat seeds. Buckwheat proteins have unique amino acid composition with special biological activities of cholesterol-lowering effects, antihypertensition effects, and improving the constipation and obisity conditions by acting similar as to dietary fiber and interrupting the in vivo metabolisms. The trypsin inhibitors isolated from buckwheat seeds are heat stable and can cause poor digestion if they are not suitably cooked before consumption. The allergenic proteins existing in the buckwheat seeds and their derivatives were reviewed with respect to their chemical and biochemical characteristics as well as the physiological reactions after digestion. Some possible mechanisms involved in these effects are discussed in this review. Experiments, both with animal models and with human beings, revealed that buckwheat flour can improve diabetes, obesity, hypertension, hypercholesterolemia and constipation. Methods to exploit buckwheat seeds and flour to produce highly effective nutraceuticals are also reviewed.

[Separation and purification of an endogenous inhibitor of sodium pump from chansu by thin-layer chromatography and reversed-phase high performance liquid chromatography].

An endogenous inhibitor of the sodium pump from the Chinese medication Chansu was purified. The dry substance Chansu was extracted with methanol. The dry residue dissolved in water and filtered subsequently through membrane filters with the exclusion size of 1000 Da, 3000 Da and 10000 Da in a Filtron Pro Vario-3-System and applied to thin-layer chromatographic plate made of Silica gel 60 F254 + 366 developed with a mixture of CHCl3-MeOH-H2O(75:20:5, volume ratio). The fractions with Rf 0.55 inhibiting the sodium pump were purified on an HPLC C18-RP column using a linear H2O-methanol gradient with 220 nm and 300 nm DAD detection. The bioactivity was measured by 86Rb-uptake into human red blood cells. The results showed that a low molecular weight, water soluble compound, which inhibited the sodium pump activity in the red blood cells and had a maximum absorbance at 250 nm was isolated from the Chinese medication Chansu. Several mg of the compound in pure state could be obtained from 1 kg Chansu. It was different from ouabain and proscillaridin A in chemical structure, because ouabain and proscillaridin A show a UV maximum absorption at 220 nm and 300 nm, while the new inhibitor at 250 nm.

[Clinical study on effect of gushukang granule in preventing and treating primary osteoporosis].

OBJECTIVE: To investigate the effect and mechanism of Gushukang granule (GSKG), a Chinese herbal preparation, in preventing and treating primary osteoporosis. METHODS: The total of 197 patients of osteoporosis, whose bone mineral density (BMD) was below 1 standard deviation of the peak bone mass of same sex, with no complications and had not been treated were selected. Among them, 176 were menopausal females for over 1 year and 21 males aged over 70. The females were voluntarily divided into three groups, the 101 cases in the observed group were treated with GSKG 12 g, three times a day and calcium carbonate 300 mg, twice a day, orally taken for 6 months; the 23 cases in the positive control group were treated with equal volume of calcium preparation alone and the 52 cases in the blank control group were untreated. All the males were treated in the same way as that in the observed group of female. The BMD level of lumbar vertebrae 2-4 and other related to indexes of bone were determined before and 6 months after treatment. RESULTS: BMD level in the two control groups lowered by 1.8% after 6 months. While in the observed group, BMD lowered slowly or even increased, after 6 months the average BMD increased by 3.1% in females and by 3.9% in males. The effective rate was 91.1% in females and 95.2% in males. After treatment, the levels of tartrate-resistant acid phosphate decreased, estradiol, testosterone and high density lipoprotein increased in the female observed group, while the obove-mentioned indexes unchanged in the control groups. CONCLUSION: GSKG has the effects in increasing sex hormones (both estrogen and androgen), inhibiting bone absorption, slowing down bone mass loss and elevating BMD, it could prevent and treat osteoporosis effectively. Besides, it could increase the level of high density lipoprotein so as to benefit prevention and treatment of cardiovascular diseases.

[Clinical observation on the treatment of ischemic heart disease with Astragalus membranaceus].

92 patients suffering from ischemic heart disease was successfully treated with Astragalus membranaceus (AM). The effect of the treatment was compared with that of Nifedipine and Tab. Salviae miltiorrhizae. The clinical practice showed that the group treated with AM yielded better results. After having administered the drug, the patients were markedly relieved from angina pectoris (heart stroke). Meanwhile the improvement of clinical objective index such as electrocardiogram (EKG) and impedance cardiogram can also be observed. The effective rate of EKG improvement was 82.6%. The treatment of ischemic heart disease with AM was significantly more effective in comparing with control group (P < 0.05).

[Prophylactic effects of zhuling and BCG on postoperative recurrence of bladder cancer].

The prophylactic effects of Chinese herbal medicine Zhuling (Grifola umbellata pilat) and BCG on bladder cancer after TURBT and partial cystectomy were evaluated. 146 patients with bladder cancer were divided into 3 groups, Zhuling, BCG, and control group. Follow-up for 48-124 months (average 70.8 months) showed that the tumor recurrence rate was 33.3%, 34.3% and 65.1%, respectively. Compared to the control group, the recurrence rate of Zhuling group and BCG group was significantly decreased (P < 0.01). The effect of Zhuling was similar to that intravesical BCG. Zhuling was cheaper and convenient in usage, and no side effects.

[Mutual influence of aminophyllin and cefotaxime in the treatment of pulmonary heart disease].

The serum Aminophyllin (TP) and Cefotaxime (CTX) concentration of the patients of pulmonary heart disease during alute attack were measured by HLPC at 2 h and 6 h after infusion. (1) TP and CTX alone were used (2) TP and CTX were used simultaneously. The result showed that the concentrations of TP were much higher, but CTX were much lower when use CTX and TP simultaneously, at 2 h and 6 h (P < 0.01, P < 0.05). The concentration of TP of pulmonary heart disease with heart failure was higher than without heart failure at 6 h when alone were used or simultaneous were used (P < 0.01), CTX wasn't correlated with heart failure. The concentrations of TP and CTX did not correlate with PaO2 and PaCO2. It showed that TP and CTX would not be used simultaneously.

Induction of tolerance to vascularised skin allografts using cyclosporin A--an experimental study on rats.

This study investigates the induction of tolerance to vascularised skin allografts in a low responder rodent strain combination. Pedicle skin grafts based on the epigastric vessels were grafted between Dark Agouti (DA) and Piebald Virol Glaxo (PVG) rats (n = 24). An extended treatment protocol of high dose cyclosporin A (CyA) (25 mg/kg) spanning nine weeks was used. The mean survival time of epigastric skin grafts in the no treatment control group was 7.6 days (n = 10). With high dose CyA (25 mg/kg), 5/14 animals died during CyA treatment with intact skin grafts. The remaining nine animals enjoyed prolonged graft survival throughout the treatment period. Between one and four weeks following cessation of CyA, rejection occurred in six of nine animals which could not be reversed by pulse CyA treatment. Long term graft survival greater than 200 days was achieved in three animals, but two animals went on to reject their grafts at 231 and 238 days post transplant. Only one animal became tolerant, as confirmed by the retention of a fresh donor-specific free skin graft, without the need for further CyA. This study confirms the difficulty of tolerance induction to vascularised skin grafts, despite using a dose schedule of CyA far in excess of that required to achieve tolerance to other solid organ grafts such as hearts.

The no-scalpel vasectomy.

A refined method of delivering the vas deferens for vasectomy has been developed and used in China since 1974. This method eliminates the scalpel, results in fewer hematomas and infections, and leaves a smaller wound than conventional techniques. An extracutaneous fixation ring clamp encircles and firmly secures the vas without penetrating the skin. A sharp curved hemostat punctures and dilates the scrotal skin and vas sheath. The vas is delivered, cleaned and occluded by the surgeon's preferred technique. The contralateral vas is delivered through the same opening. The puncture wound contracts to about 2 mm., is not visible to the man and requires no sutures for closure. The reported incidence of hematoma in 179,741 men followed in China was 0.09%. No hematomas or infections were identified in the first 273 procedures performed by a surgeon in the United States. The operating time in China and for the last 50 United States procedures has ranged from 5 to 11 minutes. The disadvantage of the technique is the hand-on training and number of cases necessary to gain proficiency. However, the advantages for surgeons and patients should enhance the popularity of vasectomy.

The use of isolated rat hepatocyte in prescreening of hepatotoxicants: observation on toxic effects of 14 compounds.

Fourteen compounds, differing in structure, mechanism of action, and primary target organs, were tested for cytotoxic responses in isolated hepatocyte suspensions prepared by a nonperfusion method from male Sprague-Dawley rats. The trypan blue exclusion test, measurement of enzyme activities in supernatants, and enzyme histochemistry were taken as indexes of cytotoxicity. All 14 compounds inhibited enzyme activities in hepatocytes. However, the activities of GOT and LDH in supernatants increased after exposure to the three haloalkanes, but decreased after exposure to the other chemicals (Na2CrO4, etc.). The number of dyed cells increased after exposure to six haloalkanes and the order of their relative toxicities in vitro was roughly in concordance with that of their in vivo hepatoxicities. These results indicate that isolated hepatocytes are useful for prescreening of potential hepatotoxicants; the so-called "enzyme leakage" should be replaced by "enzyme in supernatant" to reflect toxicities of different kinds of compounds; enzyme histochemistry is also a sensitive index in toxicological tests with isolated rat hepatocytes.