Advances in Studies of Chiglitazar Sodium, a Novel PPAR Pan-Agonist, for the Treatment of Type 2 Diabetes Mellitus.

Chiglitazar sodium is a new peroxisome proliferator-activated receptor (PPAR) pan-agonist with independent intellectual property rights in China. It can treat type 2 diabetes mellitus and regulate metabolism by modestly activating PPARα, PPARγ, and PPARδ to improve insulin sensitivity, regulate blood glucose, and promote fatty acid oxidation and utilization. Chiglitazar sodium has a significant insulin-sensitizing effect and is advantageous in reducing fasting and postprandial blood glucose levels, particularly at the 48 mg dose in patients with concomitant high triglycerides in terms of blood glucose and triglyceride level control.

Clinical comparative investigation of efficacy and toxicity of cisplatin plus gemcitabine or plus Abraxane as first-line chemotherapy for stage III/IV non-small-cell lung cancer.

PURPOSE: The purpose of this study was to observe the clinical efficacy and toxicity of cisplatin in combination with gemcitabine or Abraxane as first-line chemotherapy for stage III/IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 200 patients with advanced NSCLC, which was confirmed by pathology or cytology, were enrolled into our research by reviewing previous complete and retrievable medical records data of our hospital. A total of 100 patients were treated with gemcitabine (1,000 mg/m2, day 1 and day 8) in combination with cisplatin (75 mg/m2, days 1-3; GP group) and another 100 patients were treated with Abraxane (260 mg/m2, day 1) in combination with cisplatin (75 mg/m2, days 1-3; TP group). Twenty-one days were required to complete one cycle; at least two cycles were completed by each group. RESULTS: For the 100 patients in the GP group, the effective response rate (RR) was 27%, the disease control rate (DCR) was 63%, and the median progression-free survival (PFS) time was 8 months. For the 100 patients in the TP group, the RR was 52%, the DCR was 75%, and the median PFS was 20 months. There was significant difference in RR (P<0.001), but no significant difference in DSR and PFS (P>0.05). Common treatment-related adverse events were hematologic toxicity and gastrointestinal reaction. Hematologic toxicity mainly included decreased white blood cells and platelets. The differences between the two groups were statistically significant (P<0.05). Gastrointestinal reaction mainly included nausea and vomiting. There was no statistical significance between them (P=0.805). For the 85 patients with squamous carcinoma in the TP group, the RR was 60%, the DCR was 78%, and the median PFS was 7.5 months. For the 85 patients with squamous carcinoma in the GP group, the RR was 36%, the DCR was 62%, and the median PFS was 18.5 months. There was significant difference in RR (P=0.024), but no significant difference in DSR and PFS (P>0.05). For the 115 patients with adenocarcinoma in the TP group, the RR was 47%, the DCR was 73%, and the median PFS was 8 months. For the 115 patients with adenocarcinoma in the GP group, the RR was 20%, the DCR was 64%, and the median PFS was 20.5 months. There was significant difference in RR (P=0.003), but no significant difference in DCR and PFS (P>0.05). CONCLUSION: The efficacy of cisplatin in combination with Abraxane is better than that with gemcitabine in the treatment of NSCLC, and the treatment has less risk of hematologic toxicity.

Effects of light curing modes and ethanol-wet bonding on dentin bonding properties.

OBJECTIVE: This study explored the effects of different light curing modes and ethanol-wet bonding on dentin bonding strength and durability. METHODS: A total of 54 molars were randomly divided into three groups: Single Bond 2, Gluma Comfort Bond, and N-Bond. Based on the three light-curing modes and presence or absence of ethanol pretreatment, the samples were assigned to six subgroups: high-light mode, ethanol pretreatment+high-light mode, soft-start mode, ethanol pretreatment+soft-start mode, standard mode, and ethanol pretreatment+standard mode. All samples were bonded with resin based on the experimental groups. After 24 h and 6 months of water storage, a universal testing machine was used to measure microtensile bond strength. Scanning electron microscopy (SEM) was applied to observe mixed layer morphology. RESULTS: The 24-h and 6-month microtensile bond strengths of the ethanol pretreatment groups were significantly higher than those of the non-ethanol pretreatment groups at the same light modes (P<0.05). With or without ethanol pretreatment, the microtensile bond strengths of the high-light modes were significantly lower than those of the soft-start modes and standard modes (P<0.05). The microtensile bond strengths of samples from the 6-month water storage group significantly decreased compared with those of samples from the 24-h water storage group (P<0.05). The soft-start groups and standard groups formed better mixed layers than the high-light mode groups, whereas the ethanol pretreatment groups formed more uniform mixed layers than those without ethanol pretreatment. CONCLUSIONS: Ethanol-wet bonding technique, soft-start, and standard modes could improve dentin bonding properties.

Optimal timing of radiotherapy with alternating/sequential radio-chemotherapy for limited-stage small cell lung cancer.

OBJECTIVE: To investigate the optimal timing of radiotherapy with alternating/sequential radio-chemotherapy for limited-stage small cell lung cancer (LS-SCLC). METHODS: 91 patients with LS-SCLC were retrospectively analyzed and divided into two groups according to the number of chemotherapy cycles before radiotherapy. If the patient received radiotherapy after 3 cycles or fewer cycles of chemotherapy, classification was into the early group, if not, into the late group. All patients received 6 cycles of standard chemotherapy (EP/EC) and conventional radiotherapy (56 gy~ 60 gy/28 f ~30 f). RESULTS: The response rate (RR) of the early and late groups were 85.7% and 81.6%, respectively, with no significant difference (p>0.05). In contrast, the progression-free survival (PFS) in the early group was better than that in the late group (11.8 months vs 9.86 months), and the difference was significant (p<0.05). There was no significant difference between two groups in adverse reactions, which gastrointestinal irritation and bone marrow suppression being the most common (p>0.05). CONCLUSIONS: Radiotherapy after 3 cycles or fewer cycles of chemotherapy does not bring significant benefits for RR of patients with LS-SCLC, but it could significantly prolong their PFS without increase in adverse reactions.

[Preparation and physiochemical properties of curcumin-loaded lipid cubic liquid crystalline nanoparticles].

OBJECTIVE: To prepare curcumin-loaded lipid cubic liquid crystalline nanoparticles and evaluate its physiochemical properties. METHODS: The nanoparticles were prepared using hot and high-pressure homogenization. The prescription and preparation process were optimized by uniform design with drug loading and entrapment efficiency as indexes. RESULTS: The nanoparticles were spherical under transmission electron microscope (TEM) with average particle size of 176.1 nm, zeta potential of -25.19 mV, average drug loading of (1.5 +/- 0.2)% and entrapment efficiency of (95 +/- 1.8)%. The release equation: In (1-Q) = -0.0251t-0.0075. The cumulative release percentage was 60% at 36 h in vitro. CONCLUSION: The obtained curcumin-loaded lipid cubic liquid crystalline nanoparticles shows high entrapment efficiency and good sustain release property.

Hofmeister effects on activity and stability of alkaline phosphatase.

We have studied the effects on alkaline phosphatase of adding high concentrations (normally 1.0 M) of simple salts. It is necessary to allow for significant effects of salts on the extinction coefficient of the reaction product, and on the apparent pH of the buffer. Both activity and stability of the enzyme correlate well with the Hofmeister series in terms of the salt's kosmotropic/chaotropic properties, which are assessed by the Jones-Dole viscosity B coefficients (B(+) for cations and B(-) for anions). The catalytic activity or V(max)/K(m) of the enzyme showed a bell-shaped relationship with the (B(-)-B(+)) values of the salts present, being optimal with salts (such as NaCl, KCl, and KNO(3)) where the anion and cation have similar kosmotropic/chaotropic properties. This effect is believed to be enzyme-specific and relates to the impact of both cations and anions on the enzyme's surface pH, active site, and catalytic mechanism. Anions play a more predominant role than cations in affecting enzyme stability. The rate of irreversible thermal inactivation is strongly reduced by addition of kosmotropic anions like SO(4)(2-) (half-life increased from 8 to 580 min at 60 degrees C). This effect is general and the mechanism probably involves the ability of the ions to affect the water solvation layer around the enzyme molecule and to interact with both the surface and internal structure of the enzyme.

[Down-regulation of TopI by RNA interference reduces the drug-sensitivity of small cell lung cancer cell lines to topotecan].

OBJECTIVE: To investigate the expressions of TopI gene in small cell lung cancer cell line H446, and explore the influence of TopI on the chemosensitivity of the cell line to topotecan (TPT). METHODS: Western blot was performed to detect the TopI expression in H446 cells. Lipofectamine 2000 was used for the transient transfection of H446 cells by siRNA, and the transfection efficacy was detected. TopI mRNA was analyzed by quantitative RT-PCR and TopI protein was detected by Western blot to selected effective siRNA. The drug-sensitivity to topotecan (TPT) was evaluated by MTT assay. RESULTS: TopI gene was expressed in H446 cells. Lipofectamine 2000 mediated the siRNA effectively (88.67%). Compared with its parental cells, RT-PCR results showed that TopI mRNAs in transfected cells were reduced by (95.7 +/- 1.6)%, (90.8 +/- 1.6)%, (96.1 +/- 2.7)% and (96.3 +/- 1.8)%, respectively, and decreased significantly at protein level. By MTT assay, the inhibition rate of TPT to H446 cells transfected by siRNA was lower than that of control group at same concentrations (P < 0.01). CONCLUSION: siRNAs can silence the expression of TopI and decrease the drug-sensitivity of H446 cells to TPT.

[Expression and significance of DNA topoisomerase I (topo I) in small cell lung cancer].

OBJECTIVE: To investigate the expression and its significance of DNA topoisomerase I (Topo I) in small cell lung cancer (SCLC). METHODS: Topo I expression was detected by immunohistochemical S-P technique on 50 cases of SCLC and 12 cases of normal lung tissues. RESULTS: The total positive rate of Topo I in normal lung tissue was 25.0% (3/12) and 78.0% (39/50) in SCLC. The expression of Topo I does not correlate with age, gender, smoking, tumor size and tumor site (P > 0.05), but significantly correlated with lymph node metastasis and clinical stage (P <0.05). CONCLUSION: High Topo I expression is a rationale indication of Topo I inhibitor treatment of malignancies. It should be possible to predict anti-tumor drug sensitivity by assessment of Topo I expression and help to improve the therapeutic efficacy for cancer patients.