[Sharing Chinese experience in obesity prevention and treatment with African countries].

Obesity has become a global public health problem that seriously threatens population health. The Chinese government has attached great importance to prevent and control the negative impacts of obesity on individuals, families and society. China has established a policy system for obesity, and made certain achievements in behavioral intervention, drug treatment, traditional Chinese medicine treatment, and surgical treatment. This study summarizes the prevention and treatment experience of obesity in China in order to provide reference for African countries to better formulate prevention and treatment strategies for obesity in line with their local context.

[The status quo and analysis of quality control of cancer chemotherapy in 76 hospitals in Beijing].

Objective: Investigated the status quo of quality control of cancer chemotherapy in hospitals in Beijing to discover the main problems and provide the improvement measures. Methods: One medical record of cancer chemotherapy was taken every month for examination of quality control, and a total of 10 medical records in each hospital were examined. A total of 756 medical records from 76 hospitals were examined. Results: The results of analysis showed that the overall standardization and quality control of cancer chemotherapy was positively correlated with the grade of hospital. Only 36.8% of the hospitals were equipped with Pharmacy Intravenous Admixture Services (PIVAS). In terms of quality control of chemotherapy and medicine, the department of oncology had better performance than other departments (P<0.01). The scores of quality control of chemotherapy and medicine in the hospitals with clinical specialist pharmacists were 50.6 and 14.5, significantly higher than 47.2 and 12.7 of those without clinical specialist pharmacists (P<0.05). Conclusion: We should focus on the quality control of cancer chemotherapy in secondary hospitals, reinforce the training of oncology specialists, establish the admission system of oncologists, enhance the training of oncology clinical pharmacists and promote the standardization of cancer chemotherapy.

Cytosolic PKM2 stabilizes mutant EGFR protein expression through regulating HSP90-EGFR association.

This corrects the article DOI: 10.1038/onc.2015.397.

Cytosolic PKM2 stabilizes mutant EGFR protein expression through regulating HSP90-EGFR association.

Secondary mutation of epidermal growth factor receptor (EGFR) resulting in drug resistance is one of the most critical issues in lung cancer therapy. Several drugs are being developed to overcome EGFR tyrosine kinase inhibitor (TKI) resistance. Here, we report that pyruvate kinase M2 (PKM2) stabilized mutant EGFR protein by direct interaction and sustained cell survival signaling in lung cancer cells. PKM2 silencing resulted in markedly reduced mutant EGFR expression in TKI-sensitive or -resistant human lung cancer cells, and in inhibition of tumor growth in their xenografts, concomitant with downregulation of EGFR-related signaling. Mechanistically, PKM2 directly interacted with mutant EGFR and heat-shock protein 90 (HSP90), and thus stabilized EGFR by maintaining its binding with HSP90 and co-chaperones. Stabilization of EGFR relied on dimeric PKM2, and the protein half-life of mutant EGFR decreased when PKM2 was forced into its tetramer form. Clinical levels of PKM2 positively correlated with mutant EGFR expression and with patient outcome. These results reveal a previously undescribed non-glycolysis function of PKM2 in the cytoplasm, which contribute to EGFR-dependent tumorigenesis and provide a novel strategy to overcome drug resistance to EGFR TKIs.

Oligomycins A and C, major secondary metabolites isolated from the newly isolated strain Streptomyces diastaticus.

During the screening program for fungicides, one actinomycete strain ECO 00047 was isolated with the potential activity against fungus. According to the morphology and analysis of the nucleotide sequence of the 16S rRNA gene (1500 bp) this isolate was identified as Streptomyces diastaticus. The active compounds were separated by silica gel column chromatography, Sephadex LH-20 gel filtration and then purified by flash chromatography on C18 (20-45 microm). The chemical structure of the bioactive compounds I and II were elucidated, based on the spectroscopic data of MS, IR, UV, 1H-NMR, 13C-NMR and X-ray single crystal diffraction analysis. Compounds I and II were identical with oligomycins A and C, the macrolide antibiotics which have been known to be produced by Streptomyces diastatochromogenes, S. libani and S. avermitilis. The two compounds exhibited a strong activity against Aspergillus niger, Alternaria alternata, Botrytis cinerea and Phytophthora capsici but no activity toward bacteria. Although the two above antibiotics were known, their isolation has so far not been reported from S. diastaticus.

Pharmacokinetics, tissue distribution, and metabolism of novel DNA topoisomerase I inhibitor yuanhuacine in rabbit.

A liquid chromatography/tandem mass spectrometry method was developed and validated for the quantitative determination of yuanhuacine (YHC), a daphne diterpene ortho-ester anticancer agent, and identification of its metabolites. Pharmacokinetic behaviour, tissue distribution, and metabolism were investigated in rabbit. YHC plasma data best fitted to a two-compartment model and were characterized by an elimination half-life t(1/2)(beta) of 11.1 h following intravenous administration. Tissue distribution studies did not identify any tissues having a high affinity for YHC. The main metabolites are proposed to be M392I, M392II, and M390, resulting from the ortho-ester group and aromatic ester bond being cleaved off simultaneously during Phase I metabolism. This investigation contributes to an understanding of the metabolism of daphne diterpene ortho-esters.

Risk of betel chewing for oesophageal cancer in Taiwan.

Among 104 cases of squamous-cell oesophageal carcinoma patients and 277 controls in Taiwan, after adjusting for cigarette smoking, alcohol consumption, and other confounders, we found that subjects who chewed from 1 to 495 betel-year and more than 495 betel-years (about 20 betel quid per day for 20 years) had 3.6-fold (95% Cl = 1.3-10.1) and 9.2-fold risk (95% Cl = 1.8-46.7), respectively, of developing oesophageal cancer, compared to those who did not chew betel.

Genetic polymorphisms of XRCC1 and risk of the esophageal cancer.

A variety of environmental factors were identified to be associated with the risk of esophageal cancer. The variation in capacity of DNA repair might influence environmental chemical-associated carcinogenesis. We hypothesized that the polymorphic XRCC1 genes might modify cancer susceptibility of the esophagus. To investigate the effect of XRCC1 genetic polymorphisms on codons 194, 280 and 399, we evaluated data from 105 patients of esophageal squamous cell carcinoma and 264 healthy controls, matching with age (+/-3 years), gender and ethnicity. The distribution of the 3 genotypes were not significantly different among patients and controls. However, among alcohol drinkers, the XRCC1399 Arg/Arg genotype was more frequently found in patients with esophageal cancer. After adjustment with other environmental confounders, the OR for the genotype of XRCC1399 Arg/Arg was 2.78 (95% CI =1.15-6.67) as compared with the XRCC1(399) Arg/Gln and XRCC1(399) Gln/Gln genotypes in the alcohol drinkers. Similar trends were observed among cigarette smokers and areca chewers. However, they did not reach a statistical significance. Our findings suggest that the polymorphic XRCC1 genes might modify the risk of alcohol-associated esophageal cancers.

Proline inhibits aggregation during protein refolding.

The in vitro refolding of hen egg-white lysozyme is studied in the presence of various osmolytes. Proline is found to prevent aggregation during protein refolding. However, other osmolytes used in this study fail to exhibit a similar property. Experimental evidence suggests that proline inhibits protein aggregation by binding to folding intermediate(s) and trapping the folding intermediate(s) into enzymatically inactive, "aggregation-insensitive" state(s). However, elimination of proline from the refolded protein mixture results in significant recovery of the bacteriolytic activity. At higher concentrations (>1.5 M), proline is shown to form loose, higher-order molecular aggregate(s). The supramolecular assembly of proline is found to possess an amphipathic character. Formation of higher-order aggregates is believed to be crucial for proline to function as a protein folding aid. In addition to its role in osmoregulation under water stress conditions, the results of this study hint at the possibility of proline behaving as a protein folding chaperone.

Carbon dioxide laser surgery for snoring: results in 192 patients.

Laser-assisted uvulopalatoplasty has been introduced as an alternative to uvulopalatopharyngoplasty for treatment of snoring and potentially of obstructive sleep apnea syndrome. Between July 1994 and June 1996, 192 patients underwent 227 laser-assisted uvulopalatoplasty procedures. Loud habitual snoring was evaluated in 42 women (21.8%) and 150 men (78.2%), who were then treated with laser-assisted uvulopalatoplasty. Among the 192 patients (227 procedures), with ages from 18 to 81 years (mean 42.6 years), 15.6% (30 patients) had more than one laser-assisted uvulopalatoplasty treatment. In our series, 80 patients (42.1%) had a history of obstructive sleep apnea syndrome in addition to snoring. Laser-assisted uvulopalatoplasty treatment in patients with loud snoring resulted in elimination of snoring in 61%, partial improvement of snoring in 26%, and no improvement in 13%. The overall success rate was 87%. The mean body mass index was significantly higher in the patients with no response after the operation (27.9 kg/m2) compared with that in the patients with a good response (25.9 kg/m2). Obese (body mass index >30 kg/m2) patients were more likely to have no response to laser-assisted uvulopalatoplasty treatment of snoring than patients with an ideal body weight (body mass index <25 kg/m2) (p < 0.01). We conclude that the body mass index may be of significant value in the postoperative success rate of laser-assisted uvulopalatoplasty for the treatment of snoring.

Nasopharyngeal angiofibroma: a reappraisal of clinical features and treatment at National Taiwan University Hospital.

Nasopharyngeal angiofibroma (NAF), occurring mostly in young men, is a histologically benign tumor with aggressive clinical behavior that includes repeated epistaxis and intractable nasal obstruction. This paper reviews our recent experience at National Taiwan University Hospital (NTUH), and compares the results with those of a previous study (1955-1980) at NTUH to highlight the developments in the treatment of NAF. Fifteen patients with a diagnosis of NAF from 1984 to 1997 were included, and their clinical presentations, radiographic studies, treatments, and outcomes were retrospectively analyzed. The results showed that the clinical and demographic features were similar in the two studies. The average number of patients decreased from 2.1 patients in the previous study to 1.1 patients in this study. The duration of symptoms in the current study (8 months) was shorter than that of the previous study (16 months). Previously, the treatment consisted of radiation followed by surgery if there was residual tumor. The current treatment modality is preoperative transarterial embolization followed by surgery. The estimated intraoperative blood loss was reduced from 750 mL in the first study to 400 mL in this study. The recurrence rate decreased from 11% to 7% and the absolute relapse-free rate rose from 56% to 73%. Owing to the development of modern imaging techniques, the advent of preoperative arterial embolization, and advances in surgical techniques, successful removal of highly vascular tumors has become more feasible. Preoperative selective embolization followed by excision is an effective treatment modality. This strategy, an alternative to radiotherapy, not only avoids the long-term complications induced by radiation, but also reduces the tumor recurrence rate.

Comparison of the hemolytic activity and solution structures of two snake venom cardiotoxin analogues which only differ in their N-terminal amino acid.

Cardiotoxin analogues IV (CTX IV) and II (CTX II) isolated from the venom of Taiwan Cobra (Naja naja atra) differ in their amino acid sequence by a single amino acid at the N-terminal end. Leucine at the N-terminal end in CTX II is replaced by arginine in CTX IV. CTX IV is an unique snake venom cardiotoxin as it is the only cardiotoxin isoform known so far which possesses a positively charged residue at the N-terminal amino acid. All other cardiotoxins have a hydrophobic amino acid (leucine or isoleucine) at their N-terminal end. The aim of the present study is to understand the effect(s) of the presence of a cationic residue on the structure and functional properties of cardiotoxin(s). Comparison of the hemolytic activities of CTX IV and CTX II shows that lytic activity of the former is at least twice as that shown by the latter. Comparison of the solution structures of CTX IV and CTX II using two-dimensional NMR spectroscopy and dynamical simulated annealing technique reveals that the backbone fold of both the toxin isoforms is almost similar. The secondary structural elements in these two cardiotoxin isoforms consist of long, triple-stranded, as well as short, double-stranded, antiparallel beta-sheets. Thermal denaturation experiments showed that the structure of CTX IV is more stable than that of CTX II. Critical analysis of the three-dimensional structures of CTX IV and CTX II reveals the presence of a "cationic" cluster comprising of positively charged residues on the concave side of the CTX IV molecule. Similar clusters consisting of positively charged residues are not found in CTX II. The differential erythrocyte lytic activities of these two cardiotoxins are attributed to the difference(s) in the distribution of the positively charged residues in their three-dimensional structures.

Proline is a protein solubilizing solute.

The effect of proline on the prevention of trichloroacetic acid (TCA)-induced protein precipitation is studied. It is found that proline at high concentrations (> 4.0 M) completely prevents TCA-induced precipitation of hen egg white lysozyme. Other osmolytes such as ethylene glycol, glycerol and sucrose fail to prevent the TCA-induced precipitation of lysozyme. Viscosity and 1-anilino-8-naphthalene sulphonic acid binding experiments suggest that proline at high concentration forms an ordered supramolecular assembly. Proline is shown to increase the solubility of protein due to formation of such higher order assemblies. A model of the supra-molecular assembly of proline is proposed and a possible in vivo role of the increased levels of proline under water stress is discussed.

Effect of organic acids in the prevention of aggregation on rapid refolding of proteins.

The effect of organic acids on the aggregation of protein(s) during rapid refolding is studied. Using egg white lysozyme, it is observed that acetic acid not only prevents aggregation, but also aids the protein to refold back to its native, biologically active state. In contrast, formic acid, propionic acid and butyric acid fail to exhibit this property. Using circular dichroism spectroscopy it has been found that an 'aggregation-insensitive' partially folded intermediate state is induced in 0.35M acetic acid.

Cloning, direct expression, and purification of a snake venom cardiotoxin in Escherichia coli.

The cardiotoxin analogue III (CTX III), isolated from the Taiwan cobra (Naja naja atra) venom, is a sixty-amino acid, all beta-sheet protein. We report the direct expression of CTX III from its synthetic gene as inclusion bodies in Escherichia coli. The yield of the expressed protein is about 40 mg/liter of the culture. CTX III trapped as inclusion bodies is dissolved and refolded by the slow refolding technique. The refolded protein is purified by reverse phase high performance liquid chromatography. The purified and refolded CTX III sample is further characterized by SDS-PAGE, circular dichroism, two-dimensional NMR spectroscopy and haemolytic activity. To our knowledge, this is the first report of the direct expression and purification of snake venom cardiotoxins.