[Relationship between MTHFR Gene Polymorphism(C677T) and Adverse Reactions of High-Dose Methotrexate in Pediatric Patients with Acute Lymphoblastic Leukemia].

OBJECTIVE: To explore the effects of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism on the adverse reactions of high-dose methotrexate (MTX) in pediatric patients with acute lymphoblastic leukemia (ALL). METHODS: A total of 69 children with ALL admitted to the department of Pediatrics of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from November 2018 to October 2020 were included in this study. The clinical data of the children were collected, leukocytes were isolated from their peripheral blood, and MTHFR genotyping was performed by digital fluorescence molecular hybridization techniques. The adverse reactions and plasma drug concentration of MTX were monitored during the chemotherapy. Moreover, the effect of MTHFR gene polymorphism on MTX adverse reactions and plasma drug concentration were analyzed. RESULTS: Among the middle and high risk children, compared with the wildtype group (CC genotype), patients with MTHFR C677T mutations (CT+TT genotypes) had a higher risk of leukopenia (OR=2.38), neutropenia (OR=2.2), anemia (OR=1.83) and hepatoxicity (OR=1.98). However, no significant difference was found in the MTX plasma concentration between the MTHFR C677T mutantion group and the wildtype group at different timepoints (24 h, 48 h and 72 h). Multivariate analysis revealed that the plasma concentration of MTX (48 h), clinical risk level of ALL and MTHFR C677T gene polymorphism were independent factors for the adverse reactions of high-dose MTX. CONCLUSION: The MTHFR C677T mutations may be associated with myelosuppression and hepatotoxicity in children with ALL after high-dose MTX treatment.

[Clinical effect of digital impression combined with all-ceramic denture on restoration of 60 patients with dental defects].

PURPOSE: To analyze the clinical effect of digital impression combined with all-ceramic denture restoration on patients with dental defects. METHODS: A study was conducted on 120 patients with dental defects admitted to Dongfeng Stomatological Hospital from June 2018 to June 2020. The two groups of patients were randomly divided into digital imprinting modules and silicone rubber imprinting modules using a random number table method. There were 60 cases in each group. The silicone rubber imprint module used traditional silicone impression combined with all-ceramic denture restoration, while the digital imprint module used digital impression combined with all-ceramic denture restoration.The clinical efficacy of the two groups was observed. Gingival index (GI), periodontal index (PI) before dental restoration, during dental restoration and 6 monthes after dental restoration were compared. The adjacent surface contact conditions, occlusion and adverse reactions of the two groups were compared. SPSS 22.0 software package was used for statistical analysis. RESULTS: The two groups of patients selected grade A and grade B for the evaluation of the restoration when the restoration was completed. The number of patients who chose grade A for the digital imprint module was more than that of the silicone rubber imprint module,but there was no significant difference(P＞0.05). Six months after the tooth was worn, GI and PI indexes of the two groups of patients increased. GI and PI indexes of the silicone rubber stamping module were significantly higher than those of the digital stamping module(P＜0.05). When dental restoration was completed and 6 months after the tooth was replaced, the pass rate of contact between the adjacent surfaces of the imprinting module patients was significantly higher than that of the silicone rubber imprinting module(P＜0.05). When dental restoration was completed, the occlusion of the digital imprinting module patients was significantly better than that of the silicone rubber imprinting module(P＜0.05). Six months after wearing the denture, there was no significant difference in occlusion between the two groups of patients(P＞0.05). When dental models of the two groups of patients were taken, the incidence of adverse reactions in patients with digital imprints was significantly lower than that of silicone rubber imprints(P＜0.05). CONCLUSIONS: The use of digital impressions combined with all-ceramic restorations to repair patients with dental defects can effectively improve the treatment effect, improve prognostic GI and PI indexes of the patients, increase the pass rate of the adjacent surface contact and occlusion of the tooth, and reduce the process of dental restoration. The incidence of adverse reactions are minimal, with good prognostic effects. It is worthy of clinical application.

GKK1032B from endophytic Penicillium citrinum induces the apoptosis of human osteosarcoma MG63 cells through caspase pathway activation.

Chemical investigation of the culture extract of an endophytic Penicillium citrinum from Dendrobium officinale, afforded nine citrinin derivatives (1-9) and one peptide-polyketide hybrid GKK1032B (10). The structures of these compounds were determined by spectroscopic methods. The absolute configurations of 1 and 2 were determined for the first time by calculation of electronic circular dichroism (ECD) data. Among them, GKK1032B (10) showed significant cytotoxicity against human osteosarcoma cell line MG63 with an IC50 value of 3.49 µmol·L-1, and a primary mechanistic study revealed that it induced the apoptosis of MG63 cellsvia caspase pathway activation.

MiR-873-5p modulates progression of tongue squamous cell carcinoma via targeting SEC11A.

OBJECTIVE: To explore the effect of miR-873-5p on proliferation, apoptosis, migration, and invasion of tongue squamous cell carcinoma (TSCC) by targeting SEC11A. METHODS: Tongue squamous cell carcinoma tissues were collected and performed by qRT-PCR and Western blotting to determine the expression of miR-873-5p and SPC18. SCC9 and CAL-27 cells were transfected and divided into Mock, mimic NC, miR-873-5p mimic, SEC11A, and miR-873-5p mimic + SEC11A groups. Then, a series of experiments including cell count kit 8 (CCK-8), wound healing, Transwell, and flow cytometry were conducted. Besides, Western blotting was used to detect the expression of SPC18 and EGFR pathway-related proteins. RESULTS: MiR-873-5p was downregulated while SPC18 was upregulated in TSCC, and miR-873-5p was negatively correlated with SPC18. Dual luciferase reporter gene assay confirmed SEC11A to be a target of miR-873-5p. Cell proliferation, migration, and invasion of SCC9 and CAL-27 cells in miR-873-5p mimic group were decreased with increased cell apoptosis, presenting with downregulations of SPC18 and EGFR pathway-related proteins, while cells in SEC11A group manifested totally different changes. Moreover, the inhibitory effect of miR-873-5p mimic on TSCC cell growth was abolished by SEC11A overexpression. CONCLUSION: Overexpression of miR-873-5p may suppress cell proliferation, migration, and invasion, but facilitate apoptosis in TSCC via targeting SEC11A.

Autophagy Induced by a Novel Triazol Derivative Promotes Angiogenesis Through Decreasing Interferon-Inducible Protein 10 Level in Vascular Endothelial Cells.

ABSTRACT: Autophagy plays an important role in angiogenesis, whereas the mechanisms of vascular endothelial cell (VEC) autophagy associated with angiogenesis remain unclear. In this study, we identified a novel triazol derivative (JL025) that significantly promoted angiogenesis both in vitro and in vivo. Moreover, JL025 had no effects on cell proliferation but dramatically increased the autophagy level of VEC. The suppression of autophagy inhibited JL025-induced angiogenesis in vitro and in vivo, suggesting that JL025-induced angiogenesis was dependent on the enhanced autophagy. Mechanistic studies indicated that JL025-induced VEC autophagy was related to the Protein Kinase B/mTOR signaling pathway. Meanwhile, JL025 decreased the antiangiogenic chemokine interferon-inducible protein 10 (IP10) protein level in human VECs. Importantly, the suppression of autophagy inhibited JL025-induced decrease of IP10 protein level, indicating that autophagy mediated the degradation of IP10. Taken together, our findings provide new insights into the relationship of VEC autophagy with angiogenesis, and JL025 may have a therapeutic potential in related diseases.

Semaphorin 4A restricts tumor progression by inhibiting angiogenesis of oral squamous cell carcinoma cells.

OBJECTIVE: To investigate the effects of Semaphorin 4A (Sema4A) on the angiogenesis, migration and invasion of oral squamous cell carcinoma (OSCC) cells. METHODS: Sema4A expression in OSCC patients was detected by Immunohistochemistry, and its relationship with clinicopathological features and prognosis of patients was analyzed. The mRNA and protein expression of Sema4A in primary human oral keratinocytes (HOKs) and OSCC cells (SCC-25, HSC-3, CAL-27) were determined by Western blotting and qRT-PCR. After HOKs, HSC-3 cells and SCC-25 cells transfected with Control/Sema4A CRISPR activation plasmid, the migration and invasion abilities were detected by Wound healing and Transwell invasion. Tube formation assay was also performed on endothelial cells and the contents of VEGF and bFGF were quantified using qRT-PCR and ELISA. RESULTS: Cytoplasmic Sema4A expression was related to T classification, clinical stage and nodal metastasis of OSCC patients. Patients with low cytoplasmic Sema4A expression showed the higher microvessel density (MVD) and the poorer prognosis in OSCC. Compared with HOK, OSCC cells (SCC-25, HSC-3, CAL-27) declined apparently in Sema4A expression, which was much more significant in metastatic HSC-3 and SCC-25 cells. After HOKs, HSC-3 cells and SCC-25 cells transfected with Sema4A over-expression plasmid, the invasion and migration abilities were decreased. Besides, overexpression of Sema4A could significantly inhibit the tube formation of HUVEC induced by OSCC cells with reductions of angiogenic factors (VEGF and bFGF). CONCLUSION: Over-expression of Sema4A could restrict tumor progression through inhibiting the angiogenesis, invasion and migration of OSCC cells.

Hyperleukocytosis predicts inferior clinical outcome in pediatric acute myeloid leukemia.

OBJECTIVES: Hyperleukocytosis (HL) is a laboratory abnormality commonly presented in patients with acute myeloid leukemia (AML). However, large cohort studies on the clinical significance of HL in pediatric AML are paucity. Moreover, the effect of stem cell transplantation in HL patients remains unknown. METHODS: The clinical profiles of 885 pediatric patients with AML were downloaded from the TARGET dataset. HL was defined as an initial peripheral WBC count of ≥ 100 ×109/L. We analyzed the prevalence, clinical profile and prognosis of HL in these patients. RESULTS: The frequency of HL among all the pediatric AML was 22.6%. FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutation and gene fusion of NUP98/NSD1 occurred with higher incidence in HL patients. Overall, HL was associated with a low induction complete remission rate, and high risk of induction death. Moreover, HL predicted a significantly inferior 5-year event-free survival (EFS) (P < 0.001) and a trend of inferior 5-year overall survival (OS) (P = 0.059). However, compared with chemotherapy, stem cell transplantation had no significant effect on the survival of HL patients in terms of 5-year leukemia-free survival (P = 0.449) or OS (P = 0.447). Multivariate analysis revealed that HL was an independent prognosis factor for EFS (Hazard ratio:1.352, P = 0.013) but not for OS (Hazard ratio:1.225, P = 0.170) in pediatric AML. CONCLUSION: HL might predict inferior clinical outcome in pediatric AML. SCT is an effective therapy for AML, but it may have no better effect on the survival of patients with HL, compared to chemotherapy.

Three new spirostanol glycosides from Helleborus thibetanus.

An ongoing chemical investigation on n-BuOH extract of roots and rhizomes of Helleborus thibetanus afforded three new spirostanol glycosides (1-3). Their structures were elucidated by extensive analysis of 1 D, 2 D NMR spectra, together with IR and MS methods and acid hydrolysis. This is the first report of the isolation of spirostanol glycoside with xylose at C-24 of the aglycone in Helleborus.

Germacrane-type sesquiterpenoids with cytotoxic activity from Sigesbeckia orientalis.

Eleven new highly oxygenated germacrane-type sesquiterpenoids (1-11) and 16 known analogues (12-27) were isolated from the aerial parts of Sigesbeckia orientalis. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially NMR and ECD analyses. Compounds 13, 21 and 23 possessing an 8-methacryloxy group showed stronger in vitro cytotoxicity against human A549 and MDA-MB-231 cancer cell lines than other co-metabolites, with IC50 values ranging from 6.02 to 10.77 µM comparable to the positive control adriamycin.

The Depressive Symptoms, Resourcefulness, and Self-Harm Behaviors of Adolescents.

BACKGROUND: A report published by the World Health Organization indicates that depression typically first manifests during youth. However, adolescents usually lack the capacity for self-help or to seek help proactively from health professionals or other related resources to relieve their emotional distress. Failing to manage depression appropriately places adolescents at risk for self-harm and suicide. PURPOSE: This study explored the correlations among the depressivesymptoms, resourcefulness, and self-harm behaviors of adolescents. In addition, the impact of depressive symptoms and resourcefulness on the self-harm behaviors of adolescents was examined. METHODS: A cross-sectional and correlational design was used. One hundred forty secondary school (junior and senior high school) students in southern Taiwan were recruited for data collection using three questionnaires that measured, respectively, their depressivesymptoms, resourcefulness, and self-harm behaviors. RESULTS: Depressive symptoms and self-harm behaviors correlated significantly and positively (r = .79, p < .001). Resourcefulness correlated significantly and negatively with both depressive symptoms (r = -.35, p < .001) and self-harm behaviors (r = -.29, p < .001). Finally, depressive symptoms significantly predicted self-harm behaviors. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study provides new findings regarding the significant relationship between resourcefulness and self-harm behaviors in adolescents. Future research is suggested to explore the effect of interventions about resourcefulness training on the mental health of adolescents.

New minor spirostanol glycosides from Helleborus thibetanus.

Phytochemical reinvestigation of the dried roots and rhizomes of Helleborus thibetanus afforded four new minor spirostanol glycosides (1-4) and four known spirostanol glycosides (5-8). Their structures were determined on the basis of spectroscopic analyses, including 1D and 2D NMR experiments, together with HR-ESI-MS and IR measurements and the results of acid hydrolysis.

Three new steroidal saponins from Helleborus thibetanus.

Three new steroidal saponins including two spirostanol glycosides (1-2) and one furostanol glycoside 1-sulphate (3) were isolated from the dried roots and rhizomes of Helleborus thibetanus. Structures of the compounds were determined on the basis of extensive use of 1-D and 2-D NMR experiments, together with HR-ESI-MS and IR measurements, as well as the results of acid hydrolysis. Compounds 1-2 represented steroidal saponins with an unusual substitution pattern, which possessed a double bond at C-25 and were glycosylated at 1-OH.

Broadband focusing and demultiplexing of surface plasmon polaritons on metal surface by holographic groove patterns.

Manipulation of surface plasmon polaritons (SPPs) on metal surfaces is important for constructing ultracompact integrated micro/nano optical devices and systems. We employ the method of surface electromagnetic wave holography (SWH) to design holographic groove patterns for managing the transport of broadband SPPs on metal surface. Several sets of groove patterns corresponding to different wavelengths are etched on the same region on metal surface to form a broadband SPP hologram. The incident SPPs are scattered by the composite hologram and interfere with each other to focus at different or the same positions for SPPs of different wavelengths. Finite-difference time-domain simulations show that broadband demultiplexing of SPPs is realized by the designed plasmonic holographic structures. In addition, the broadband SPPs can be focused to a pre-designated spot by a designed plasmonic hologram and as a result focusing of an ultrashort plasmonic pulse can be achieved. The results show that the SWH can successfully handle design of plasmonic holographic structures for SPPs wavelength management on metal surface.

The use of zein and Shuanghuangbu for periodontal tissue engineering.

AIM: Tissue engineering is a promising area with a broad range of applications in the fields of regenerative medicine and human health. The emergence of periodontal tissue engineering for clinical treatment of periodontal disease has opened a new therapeutic avenue. The choice of scaffold is crucial. This study was conducted to prepare zein scaffold and explore the suitability of zein and Shuanghuangbu for periodontal tissue engineering. METHODOLOGY: A zein scaffold was made using the solvent casting/particulate leaching method with sodium chloride (NaCl) particles as the porogen. The physical properties of the zein scaffold were evaluated by observing its shape and determining its pore structure and porosity. Cytotoxicity testing of the scaffold was carried out via in vitro cell culture experiments, including a liquid extraction experiment and the direct contact assay. Also, the Chinese medicine Shuanghuangbu, as a growth factor, was diluted by scaffold extract into different concentrations. This Shuanghuangbu-scaffold extract was then added to periodontal ligament cells (PDLCs) in order to determine its effect on cell proliferation. RESULTS: The zein scaffold displayed a sponge-like structure with a high porosity and sufficient thickness. The porosity and pore size of the zein scaffold can be controlled by changing the porogen particles dosage and size. The porosity was up to 64.1%-78.0%. The pores were well-distributed, interconnected, and porous. The toxicity of the zein scaffold was graded as 0-1. Furthermore, PDLCs displayed full stretching and vigorous growth under scanning electronic microscope (SEM). Shuanghuangbu-scaffold extract could reinforce proliferation activity of PDLCs compared to the control group, especially at 100 microg x mL(-1) (P < 0.01). CONCLUSION: A zein scaffold with high porosity, open pore wall structure, and good biocompatibility is conducive to the growth of PDLCs. Zein could be used as scaffold to repair periodontal tissue defects. Also, Shuanghuangbu-scaffold extract can enhance the proliferation activity of PDLCs. Altogether, these findings provide the basis for in vivo testing on animals.

Role of the Chinese herbal medicine xianhuayin on the reversal of premalignant mucosal lesions in the golden hamster buccal pouch.

AIM: To investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene (DMBA)-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters. METHODOLOGY: The animals were randomly divided into a non-diseased control group (n=5) and an experimental group including 50 animals in which the buccal mucosa had been painted with DMBA (0.5% in acetone) to generate an oral mucosa premalignant lesion. Animals in the experimental group were further divided into Xianhuayin-treated group (n=30), untreated premalignant lesion group (n=10) and normal saline (NS)-treated group (n=10). The cheek (buccal) pouch mucosa of the golden hamsters in each group was observed with light and electron microscopy eight weeks after intragastric administration with NS or Xianhuayin. RESULTS: In the non-diseased control group, the buccal mucosa was keratinized and stratified squamous epithelium under a light microscope. In the untreated premalignant lesion group, variable degrees of epithelial dysplasia was observed. The irregular epithelial mucosa gradually became distinct in the Xianhuayin-treated group. Scanning electronic microscopic (SEM) analysis showed that surface of the cells exhibited honeycomb structures in the hamster of untreated-group. The cells were morphologically irregular, overlapped and loosened in the untreated premalignant lesion group. Most of the cell surface exhibited honeycomb structure in the Xianhuayin-treated group. Transmission electronic microscopic (TEM) analysis showed that buccal mucosal epithelial cells were morphologically regular in the non-diseased control group. Desmosomes and tonofibrils were reduced and the nucleus was morphologically irregular in the untreated premalignant lesion group. In the Xianhuayin-treated group, the widening intercellular gap was gradually reduced, desmosomes and the cells becoming morphologically regular. No significant difference was observed between the hamsters in NS-treated group and those in the untreated premalignant lesion group. Significant therapeutic efficacy was observed in the group receiving Xianhuayin. CONCLUSION: Xianhuayin is effective in the reversal of DMBA-induced premalignant lesions in the buccal pouch of golden hamsters.

[Features of insulin secretion and insulin resistance in newly diagnosed type 2 diabetes of different body mass indices].

OBJECTIVE: To investigate insulin secretion function and insulin resistance in Chinese newly diagnosed type 2 diabetes (obese and non-obese patients) in order to provide evidence for clinical treatment. METHODS: 408 newly diagnosed type 2 diabetes and 40 normal controls were recruited. Height, weight were measured, insulin and glucose of 0 min, 30 min, 60 min, 120 min during oral glucose tolerance test were examined. The patients with fasting glucose level greater than 8.3mmol/L were treatment with Gliclazide for 1 - 3 months. After normalization of the plasma glucose levels for more than 2 weeks, and withdraw this medication for 48 hours, then OGTT were repeated to assess IR and IS. RESULTS: The patients were divided into four groups based on fasting plasma glucose (DM1: FPG < 6.9mmol/L; DM2: 6.9 mmol/L < or = FPG < 8.3 mmol/L; DM3: 8.3 mmol/L < or = FPG < 9.7 mmol/L; DM4: FPG > or = 9.7 mmol/L). Every groups were further stratified to subgroups by cut point of BMI = 24 kg/m(2). Their insulin sensitivity and insulin secretion function compared between subgroups. (1) True insulin level in BMI > or = 24 (FPG < 6.9 mmol/L) subgroups were higher than control's (3.5 +/- 0.5 vs 3.2 +/- 0.6 natural logarithm) (P < 0.05). (2) In BMI > or = 24 subgroups, their insulin sensitivity were even worse than BMI < 24 groups', but their insulin secretion function were better at the same FPG level. (3) After intervention, the change of insulin sensitivity in BMI < 24 group was better than BMI > or = 24 group's (-4.7 +/- 0.9 vs -5.5 +/- 1.4 natural logarithm) (P < 0.05); but the change of insulin secretion function in BMI < 24 group was worse. CONCLUSION: (1) In newly diagnostic type 2 diabetes, insulin sensitivity and insulin secretion function were decreased with the increase of FPG, but they were different between obese and non-obese group. (2) Insulin secretion function was recovered better in obese group when eliminated glucose toxicity.

[Changes of the content of Se and the levels of several cytokines in the serum of patients with Kaschin-Beck disease].

AIM: To investigate the levels of selenium (Se) and several cytokines (TNF-alpha, VEGF and IL-1beta) in the serum of patients with Kaschin-Beck disease (KBD). METHODS: 90 subjects were selected, from KBD areas and non-KBD areas of Lhasa, Tibet. Then they were divided into 3 groups: the group with KBD (30), the control in KBD areas (30), and the control in non-KBD areas (30). There was no obvious difference in sex and age in the three groups. The content of Se in the serum was detected by atomic fluorescent spectrometer and the level of cytokines (TNF-alpha, VEGF and IL-1beta) in the serum were detected by ELISA. RESULTS: The content of Se in the serum of persons living in the KBD-disease areas were lower than that of persons living in non-KBD disease areas. The levels of TNF-alpha, VEGF and IL-beta in KBD group were higher than those in normal control group (P<0.05). The content of Se had negative correlation with the levels of TNF-alpha and IL-beta in serum. CONCLUSION: The decrease of Se content and increase of the levels of TNF-alpha, VEGF and IL-1beta may play a role in pathogenesis of KBD.

[Effects of sibutramine on blood glucose and lipids, body fat mass and insulin resistance in obese patients: a multi-center clinical trial].

OBJECTIVE: To evaluate the effects of sibutramine on body weight, body fat mass, metabolism of plasma glucose and serum lipids, and insulin resistance (IR) in primary obesity patients. METHODS: A double-blind, double-placebo, randomized controlled, multi-center clinical trial was conducted. 359 voluntary obese subjects, whose body mass index (BMI) > or = 27 kg/m(2), without hypertension and diabetes, were enrolled. They were randomly divided into group A, B and C respectively. Sibutramine tablets or capsules were administered 10-20 mg/day for 24 weeks to the test groups and placebo to a control group. CT scan was used to measure the intra or subcutaneous-abdominal fat areas (IAFA, SAFA) at L(4)-L(5) level. Dual energy X-ray absorptiometry (DEXA) was used to measure total body fat mass (TBFM). RESULTS: 315 subjects continued to be followed for 24 weeks. After opening the blind, it was shown that group A received sibutramine tablet (n = 107), group B placebo (n = 104) and group C was capsule (n = 104). In group A and C body weight loss was 4.86 kg (6.42%) and 4.68 kg (6.38%), TBFM reduction was 4.07 kg (13.94%) and 4.09 kg (15.02%), SAFA decreased 7.30% and 7.45%, IAFA decreased 19.21% and 16. 98% respectively. Fasting plasma glucose decreased from 5.69 to 4.83 mmol/L and from 5.38 to 4.69 mmol/L in group A and C respectively. Fasting serum insulin decreased from 20.98 to 14.75 mU/L and from 21.11 to 14.68 mU/L, 2 h insulin decreased from 70.91 to 44.11 mU/L and from 73.13 to 41.93 mU/L in group A and C respectively. Serum triglyceride decreased from 1.98 to 1.73 mmol/L and 1.84 to 1.67 mmol/L, total cholesterol decreased from 5.08 to 4.75 mmol/L and from 5.06 to 4.46 mmol/L, high-density lipoprotein cholesterol increased from 1.13 to 1.28 mmol/L and 1.10 to 1.31 mmol/L in group A and C respectively, HOMA-IR index decreased from 5.32 to 3.32, and from 5.09 to 3.12 respectively in group A and C. Adverse drug reaction was 32.41%, 13.47% and 31.20% in group A, B and C. CONCLUSIONS: Sibutramine tablet or capsule decreases comparably body weight and TBFM, especially IAFA regulates plasma glucose and serum lipid metabolism and also decreases IR. Sibutramine is well tolerated in most of the subjects.