Au@SiO2@CuInS2-ZnS/Anti-AFP fluorescent probe improves HCC cell labeling.

BACKGROUND: Clear tumor imaging is essential to the resection of hepatocellular carcinoma (HCC). This study aimed to create a novel biological probe to improve the HCC imaging. METHODS: Au nano-flower particles and CuInS2-ZnS core-shell quantum dots were synthesized by hydrothermal method. Au was coated with porous SiO2 and combined with anti-AFP antibody. HCC cell line HepG2 was used to evaluate the targeting efficacy of the probe, while flow cytometry and MTT assay were used to detect the cytotoxicity and bio-compatibility of the probe. Probes were subcutaneously injected to nude mice to explore light intensity and tissue penetration. RESULTS: The fluorescence stability of the probe was maintained 100% for 24 h, and the brightness value was 4 times stronger than that of the corresponding CuInS2-ZnS quantum dot. In the targeting experiment, the labeled HepG2 emitted yellow fluorescence. In the cytotoxicity experiments, MTT and flow cytometry results showed that the bio-compatibility of the probe was fine, the inhibition rate of HepG2 cell with 60% Cu-QDs/Anti-AFP probe and Au-QDs/Anti-AFP probe solution for 48 h were significantly different (86.3%±7.0% vs. 4.9%±1.3%, t = 19.745, P<0.05), and the apoptosis rates were 83.3%±5.1% vs. 4.4%±0.8% (P<0.001). In the animal experiment, the luminescence of the novel probe can penetrate the abdominal tissues of a mouse, stronger than that of CuInS2-ZnS quantum dot. CONCLUSIONS: The Au@SiO2@CuInS2-ZnS/Anti-AFP probe can targetedly recognize and label HepG2 cells with good bio-compatibility and no toxicity, and the strong tissue penetrability of luminescence may be helpful to surgeons.

Bio-compatibility and cytotoxicity studies of water-soluble CuInS2-ZnS-AFP fluorescence probe in liver cancer cells.

BACKGROUND: The oncogenesis of hepatocellular carcinoma (HCC) is not clear. The current methods of the pertinent studies are not precise and sensitive. The present study was to use liver cancer cell line to explore the bio-compatibility and cytotoxicity of ternary quantum dots (QDs) probe and to evaluate the possible application of QDs in HCC. METHODS: CuInS2-ZnS-AFP fluorescence probe was designed and synthesized to label the liver cancer cell HepG2. The cytotoxicity of CuInS2-ZnS-AFP probe was evaluated by MTT experiments and flow cytometry. RESULTS: The labeling experiments indicated that CuInS2-ZnS QDs conjugated with AFP antibody could enter HepG2 cells effectively and emit intensive yellow fluorescence by ultraviolet excitation without changing cellular morphology. Toxicity tests suggested that the cytotoxicity of CuInS2-ZnS-AFP probe was significantly lower than that of CdTe-ZnS-AFP probe (t test, F=0.8, T=-69.326, P<0.001). For CuInS2-ZnS-AFP probe, time-effect relationship was presented in intermediate concentration (>20%) groups (P<0.05) and dose-effect relationship was presented in almost all of the groups (P<0.05). CONCLUSION: CuInS2-ZnS-AFP QDs probe had better bio-compatibility and lower cytotoxicity compared with CdTe-ZnS-AFP probe, and could be used for imaging the living cells in vitro.

Synthesis and antitumor activity of novel 2-substituted indoline imidazolium salt derivatives.

A series of novel 2-substituted indoline imidazolium salt derivatives has been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the existence of a substituted benzimidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl or 2-naphthylmethyl group were vital for modulating the cytotoxic activity. Compound 25 was found to be the most potent derivative with IC50 values of 0.24-1.18 µM, and exhibited cytotoxic activity selectively against MCF-7, SW480, SMMC-7721 and HL-60 cell lines, while compound 26 showed powerful inhibitory activities selectively against SMMC-7721 and A549 cell lines. Compound 25 can induce G2/M phase cell cycle arrest and apoptosis in SMMC-7721 cells.

Synthesis and cytotoxic activity of novel 1-((indol-3-yl)methyl)-1H-imidazolium salts.

A series of novel 1-((indol-3-yl)methyl)-1H-imidazolium salts were prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the 5,6-dimethyl-benzimidazole ring, and substitution of the imidazolyl-3-position with a naphthylacyl or 4-bromophenacyl group, were vital for modulating inhibitory activity of cell growth. In particular, 1-((N-Boc-indol-3-yl)methyl)-3-(2-naphthylacyl)-1H-5,6-dimethyl-benzimidazolium bromide was found to be the most potent derivative and more selective against myeloid liver carcinoma (SMMC-7721), lung carcinoma (A549) and breast carcinoma (MCF-7), with IC50 values 1.9-fold, 1.7-fold and 4.8-fold lower than DDP. This compound can induce significant cell apoptosis in SMMC-7721 cells.

Clinical Application and Synthesis Methods of Deuterated Drugs.

Many drugs have adverse absorption, distribution, metabolism, and excretory (ADME) properties that prevent their widespread use or limit their use in some indications. In addition to preparation techniques and prodrug strategies, deuterium modification is a viable method for improving ADME properties. Deuterated drugs have attracted increasing attention from the pharmaceutical industry in recent years. To date, two deuterated drugs have been approved by the FDA. In 2017, austedo was approved by the FDA as a new drug for Huntington's disease in the United States, the first deuterium drug to be marketed worldwide. Recently (June 9, 2021), donafinil has been listed in China; this result has caused major pharmaceutical companies and the pharmaceutical industry to pay attention to deuterium technology again. In addition, BMS-986165, RT001, ALK-001, HC-1119, AVP-786 and other drugs are in phase III clinical studies, and some solid deuterium compounds have entered phase I and II clinical trials. The deuterium strategy has been widely used in pharmaceutical research and has become a hot spot in pharmaceutical research in recent years. In this paper, the research and development of deuterated drugs are reviewed, and the influence of deuterium modification on drugs, the advantages of deuterium strategies and the synthesis strategies of deuterated drugs are mainly introduced. Hoping to provide references for clinical application, the discovery of new deuterium chemical entities and research and development of new deuterated drugs.

Asymmetric figure-of-eight single-layer suture technique for intestinal anastomosis: A preliminary study.

Background: Anastomotic leakage is a life-threatening complication. Improvement of the anastomosis technique is needed, especially in patients with an inflamed edematous intestine. The aim of our study was to evaluate the safety and efficacy of an asymmetric figure-of-eight single-layer suture technique for intestinal anastomosis in pediatric patients. Methods: A total of 23 patients underwent intestinal anastomosis at the Department of Pediatric Surgery of Binzhou Medical University Hospital. Demographic characteristics, laboratory parameters, anastomosis time, duration of nasogastric tube placement, day of first postoperative bowel movement, complications, and length of hospital stay were statistically analyzed. The follow-up was conducted for 3-6 months after discharge. Results: Patients were divided into two groups: the single-layer asymmetric figure-of-eight suture technique (group 1) and the traditional suture technique (group 2). Body mass index in group 1 was lower than in group 2 (14.43 ± 3.23 vs. 19.38 ± 6.74; P = 0.036). The mean intestine anastomosis time in group 1 (18.83 ± 0.83 min) was less than that in group 2 (22.70 ± 4.11 min; P = 0.005). Patients in group 1 had an earlier first postoperative bowel movement (2.17 ± 0.72 vs. 2.80 ± 0.42; P = 0.023). The duration of nasogastric tube placement in group 1 was shorter than that in group 2 (4.12 ± 1.42 vs. 5.60 ± 1.57; P = 0.043). There was no significant difference in laboratory variables, complication occurrence, and length of hospital stay between the two groups. Conclusion: The asymmetric figure-of-eight single-layer suture technique for intestinal anastomosis was feasible and effective. More studies are needed to compare the novel technique with the traditional single-layer suture.

Research Status, Synthesis and Clinical Application of Recently Marketed and Clinical BCR-ABL Inhibitors.

Tyrosine kinases expressed by BCR-ABL fusion genes can cause changes in cell proliferation, adhesion, and survival properties, which are the main causes of chronic myelogenous leukemia (CML). Inhibiting the activity of BCR-ABL tyrosine kinase has become one of the effective methods for the treatment of chronic myelogenous leukemia. Initially, imatinib was the first small molecule of BCR-ABL tyrosine kinases inhibitors (TKIs) for the effective treatment of chronic myelogenous leukemia. Later, due to the emergence of various BCR-ABL mutations, especially T315I mutation, imatinib developed strong resistance. The second-generation kinase inhibitors dasatinib and nilotinib were able to overcome most of the mutation resistance but not T315I mutations. Therefore, in order to further overcome the problem of drug resistance, new types of KTIs such as flumatinib and radotinib have been developed, providing more options for clinical treatment. Some new drugs have entered clinical trials. In this review, two new BCRABL inhibitors (flumatinib and radotinib) and five new BCR-ABL inhibitors have been introduced into the clinical market in recent years. We reviewed their research status, synthesis methods, and clinical applications.

The use of carcinoembryonic antigen levels to predict lung nodule malignancy: a meta-analysis.

OBJECTIVES: To assess the diagnostic value of serum carcinoembryonic antigen (CEA) as a diagnostic biomarker that can be used to differentiate between benign and malignant lung nodules (LNs). METHODS: PubMed, Cochrane Library, and Embase were reviewed from January 2000 to April 2020 for eligible studies. Stata v12.0 was used to conduct this meta-analysis. RESULTS: Our initial literature search identified 511 potentially relevant studies, of which 11 were ultimately included in the present meta-analysis. Ten studies were retrospective and only 1 study was prospective. Overall these studies incorporated 2760 patients and 2760 total LNs (1733 malignant, 1027 benign). Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) values for these studies were 0.33 (95% CI: 0.20-0.49), 0.92 (95% CI: 0.85-0.96), 3.96 (95% CI: 2.84-5.54), 0.73 (95% CI: 0.62-0.87), and 5.42 (95% CI: 3.77-7.78), respectively. The area under curve (AUC) value was 0.77, consistent with moderate diagnostic accuracy. We detected significant heterogeneity when calculating pooled sensitivity (I2 = 95.9%, P = 0.00), specificity (I2 = 92.0%, P = 0.00), PLR (I2 = 61.7%, P = 0.00), NLR (I2 = 92.8%, P = 0.00), and DOR (I2 = 93.8%, P = 0.00). No significant evidence of publication bias was detected via Deeks' funnel plot asymmetry test (P = 0.371). Meta-regression analysis revealed different reference standards to be closely associated with both sensitivity and specificity. CONCLUSIONS: Serum CEA can achieve moderate diagnostic performance as a means of differentiating between malignant and benign LNs.

Benign pathologies results from lung nodule percutaneous biopsies: How to differentiate true and false benign?

OBJECTIVES: The objective was to identify predictors of true negatives in lung nodules (LNs) with computed tomography-guided percutaneous biopsy (CTPB)-based benign pathological results. MATERIALS AND METHODS: We included 90 total patients between January 2013 and December 2017 that had CTPB-based nonspecific benign pathologies and used these patients as a training group to accurately identify true-negative predictors. A validation group of 50 patients from January 2018 to June 2019 to confirm predictor reliability. RESULTS: CTPB was conducted on 90 LNs from the training group. True-negative and false-negative CTPB-based pathologies were obtained for 79 and 11 LNs, respectively. CTPB-based benign results had a negative predictive value of 87.8% (79/90). Univariate and multivariate analyses revealed younger age (P = 0.019) and CTPB-based chronic inflammation with fibroplasia (P = 0.010) to be true-negative predictors. A predictive model was made by combining these two prognostic values as follows: score = -7.975 + 0.112 × age -2.883 × CTPB-based chronic inflammation with fibroplasia (0: no present; 1: present). The area under receiver operator characteristic (ROC) curve was 0.854 (P < 0.001). To maximize sensitivity and specificity, we selected a cutoff risk score of -0.1759. The application of this model to the validation group yielded an area under the ROC curve of 0.912 (P < 0.001). CONCLUSIONS: Our predictive model showed good predictive ability for identifying true negatives among CTPB-based benign pathological results.

SPP1 and FN1 are significant gene biomarkers of tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumor types in the oral and maxillofacial region. The etiology and pathogenesis behind TSCC is complicated. In the present study, three gene expression profiles, namely GSE31056, GSE13601 and GSE78060, were downloaded from the Gene Expression Omnibus (GEO). The GEO2R online tool was utilized to identify differentially expressed genes (DEGs) between TSCC and normal tissue samples. Furthermore, a protein-protein interaction (PPI) network was constructed and hub genes were validated and analyzed. A total of 83 common DEGs were obtained in three datasets, including 48 upregulated and 35 downregulated genes. Pathway enrichment analysis indicated that DEGs were primarily enriched in cell adhesion, extracellular matrix (ECM) organization, and proteolysis. A total of 63 nodes and 218 edges were included in the PPI network. The top 11 candidate hub genes were acquired, namely plasminogen activator urokinase (PLAU), signal transducer and activator of transcription 1, C-X-C motif chemokine ligand 12, matrix metallopeptidase (MMP) 13, secreted phosphoprotein 1 (SPP1), periostin, MMP1, MMP3, fibronectin 1 (FN1), serpin family E member 1 and snail family transcriptional repressor 2. Overall, 83 DEGs and 11 hub genes were screened from TSCC and normal individuals using bioinformatics and microarray technology. These genes may be used as diagnostic and therapeutic biomarkers for TSCC. In addition, SPP1 and FNl were identified as potential biomarkers for the progression of TSCC.

Measurement and prediction on thermal conductivity of fused quartz.

Thermal conductivity of soil is a basic physical property related to heat conduction, and also is one of parameters widely applied in geotechnical engineering. The effect of gradation on the thermal conductivity of fused quartz was analyzed by thermal needle tests. The different particle size with the same uniformity coefficient (Cu = 3.2) and different uniformity coefficient for the same particle size (0.10~1.00 mm) were considered in this study. It shows that the thermal conductivity of fused quartz decreases with the decreasing of the mean particle size and with the increasing of the porosity. Simple modified methods to estimate the value of thermal conductivity are proposed, and had been demonstrated successfully by conducting fused quartz, carbonate sand and Ottawa sand.

Alternative technique to save ischemic bowel segment in management of neonatal short bowel syndrome: A case report.

BACKGROUND: Congenital short bowel syndrome (SBS) associated with malrotation, gut volvulus and jejuno-ileal atresia is a very rare condition. It is a severe challenge for surgeons to preserve residual ischemic bowel segment in the management of short bowel syndrome,especially in neonates. CASE SUMMARY: We report a newborn baby with gut malrotation associated with jejuno-ileal atresia, congenital SBS and jejunal volvulus. Hematemesis and abdominal distention were noted. At laparotomy, malrotation associated with jejuno-ileal atresia, congenital SBS and jenunal volvulus was confirmed. The total length of the small bowel was 63 cm with proximal jejunal bowel segment measuring 38 cm, including 18 cm necrotic segment below the Treitz's ligament and 20 cm severe ischemic segment. The distal part of the small bowel was 25 cm in length and only about 0.8 cm in diameter. Ladd's procedure, necrotic segment resection and end-to-back duodeno-ileal anastomosis were performed. The residual severe ischemic jejunum was preserved with single proximal stoma and distal end closure. Three months later, to restore the continuity of the isolated gut segment, end-to-end duodeno-jejunal and jejuno-ileal anastomosis was performed. The entire functional small bowel length increased to 80 cm. Intravenous fluid therapy and parenteral nutrition were discontinued on the 10th day postoperatively. Twelve months later, her body weight was 9.5 kg. CONCLUSION: Isolation of severe ischemic bowel segment and staged anastomosis to restore the gut continuity for infants with SBS are safe and feasible.

Raman analysis of CdSe/CdS core-shell quantum dots with different CdS shell thickness.

We report the first-order and high-order Raman scattering from core-shell CdSe/CdS nanocrystals and investigate the evolution of the longitudinal mode of CdSe (LO1) and CdS (LO2), and the surface mode of CdSe (SO1) and CdS (SO2) with increasing shell thickness (0-5.5 ML (monolayer)). We find that the shift of the LO2 peak from 268 to 291 cm(-1) agrees well with the theoretical values based on the phonon confinement model. The variation of the dielectric environment of the CdSe core with increasing CdS shell thickness is modified according to the shift of SO1 from 198 to 185 cm(-1). The SO2 modes at 267 and 275 cm(-1), corresponding to the shell thickness 3.5 and 5.5 ML in CdSe/CdS nanocrystals, respectively, are also obtained for the first time in our experiment. Moreover, they agree well with the theoretical values of the dielectric corresponding function model. Besides, a new Raman peak at 482 cm(-1) is observed, and it remains at that value with shell growth, the new peak is supposed to be caused by the alloying at the core-shell interface. Therefore, Raman spectroscopy can be used to determine the shell thickness and other surface and interface parameters of CdSe/CdS core-shell nanocrystals.

Construction of eukaryotic expression plasmid containing HCV NS3 segment and protein expression in human HL-7702 hepatocytes.

AIM: To construct the eukaryotic expression plasmid containing HCV NS3 segment and to analyze the expression of NS3 protein in normal human hepatocyte HL-7702. METHODS: We amplified HCV NS3 fragment from plasmid pBRTM/HCV 1-3011 containing the whole length of HCV genome, recombined it with expression vector pcDNA3.1(-) to form the eukaryotic expression vector pcDNA3.1(-)/NS3, and transfected human HL-7702 hepatocytes with the recombined plasmid by cationic polymers. The expressed HCV NS3 protein was detected and analyzed by immunohistochemical method and Western blot. RESULTS: The amplified NS3 fragments had correct molecule weight and sequence. The successfully constructed eukaryotic expression plasmids were transfected to HL-7702 cells. The expressed NS3 proteins had correct molecular weight 70000. CONCLUSION: Eukaryotic expression vector pcDNA3.1 (-)/NS3 containing NS3 segment of HCV can be constructed, the sequence of NS3 fragments is consistent with the template. Normal human HL-7702 hepatocytes can efficiently express specific HCV NS3 protein in vitro.

Association of IL12B Gene Polymorphisms with Rheumatoid Arthritis: A Meta-analysis.

BACKGROUND AND AIMS: Currently published papers regarding the relationship between interleukin (IL)-12B gene polymorphisms and rheumatoid arthritis (RA) are contradictory. The aim of this meta-analysis was to evaluate the associations between the IL-12B gene polymorphisms (rs3122227 and rs6887695) and RA risk. METHODS: We searched PubMed, Embase, the Cochrane Library and the China Knowledge Resource Integrated Database. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess associations between IL12B gene polymorphisms and RA. RESULTS: A total of eight publications (4,409 cases and 5,591 controls) were included in this meta-analysis. The results demonstrated that rs3122227 and rs6887695 were not associated with RA risk based on current included studies. However, stratification analyses indicated rs6887695 was associated with RA in Asian patients. Rs3122227 was not related with RA in Asian or Caucasian patients. CONCLUSIONS: Our data indicated that IL-12B gene polymorphisms were not related with RA. However, rs6887695 was associated with RA in Asian patients. Further larger-scale studies are urgently needed to identify the association between IL-12B gene polymorphisms and RA in Asian populations.

The associations between MDM4 gene polymorphisms and cancer risk.

Considerable studies have investigated the associations between MDM4 gene polymorphisms and cancer risk recently, but with contradictory results. The aim of this meta-analysis was to evaluate the associations between MDM4 gene polymorphisms and cancer risk. Relevant studies were identified by a systematic search of PubMed, Embase, and CNKI databases. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of the associations. Fifty-six studies published in 11 publications involving 18,910 cases and 51,609 controls were included in this meta-analysis. Five MDM4 gene polymorphisms were evaluated: rs4245739, rs1563828, rs11801299, rs10900598, and rs1380576. Our analyses suggested that the rs4245739 polymorphism was significantly associated with overall cancer risk. Furthermore, stratification analyses of ethnicity indicated that rs4245739 decreased the risk of cancer among the Asian population, and stratification analyses of smoking status indicated that rs4245739 decreased the risk of cancer among nonsmokers. However, stratification analyses of cancer type and sex suggested that rs4245739 was not related to cancer risk. There were no associations of rs1563828, rs11801299, rs10900598, or rs1380576 with overall cancer risk. In conclusion, our analyses indicated that rs4245739 polymorphism in the MDM4 gene may play an important role in the etiology of cancer.

MYO9B gene polymorphisms are associated with the risk of inflammatory bowel diseases.

Myosin IXB (MYO9B) gene polymorphisms have been extensively investigated in terms of their associations with inflammatory bowel disease (IBD), with contradictory results. The aim of this meta-analysis was to evaluate associations between MY09B gene polymorphisms and the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Eligible studies from PubMed, Embase, and CNKI databases were identified. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Ten studies published in eight papers reporting 8,975 cases and 9,482 controls were included in this meta-analysis. Five MY09B gene polymorphisms were evaluated: rs1545620, rs962917, rs1457092, rs2305764, and rs2305767. Our data suggested that the rs1545620 polymorphism was associated with a decreased risk of IBD. A similar result was found for rs2305767 and UC. The rs962917 single nucleotide polymorphism (SNP) increased the risk of IBD, CD and UC. Moreover, rs1457092 increased the risk of IBD and UC. Rs2305764 was also associated with an increased risk of IBD. Furthermore, stratification analyses indicated that rs1545620 decreased the risk of IBD, while rs962917 increased the risk of IBD, CD and UC in Caucasian populations. To sum up, our data indicate that these five SNPs in MY09B are significantly associated with the risk of IBD.

Ectopic bone formation of human bone morphogenetic protein-2 gene transfected goat bone marrow-derived mesenchymal stem cells in nude mice.

OBJECTIVE: To evaluate the osteogenic potential of bone morphogenetic protein (BMP)-2 gene transfected goat bone marrow-derived mesenchymal stem cells (MSCs). METHODS: Goat bone marrow-derived MSCs were transfected by Adv-human bone morphogenetic protein (hBMP)-2 gene (Group 1), Adv-beta gal transfected MSCs (Group 2) and uninfected MSCs (Group 3). Western blot analysis, alkaline phosphatase staining, Von Kossa staining and transmission electron microscopy were adopted to determine the phenotype of MSCs. Then the cells were injected into thigh muscles of the nude mice. Radiographical and histological evaluations were performed at different intervals. RESULTS: Only Adv-hBMP-2 transfected MSCs produced hBMP-2. These cells were positive for alkaline phosphatase staining at the 12th day and were positive for Von Kossa staining at the 16th day after gene transfer. Electron microscopic observation showed that there were more rough endoplasmic reticulum, mitochondria and lysosomes in Adv-hBMP-2 transfected MSCs compared to MSCs of other two groups. At the 3rd and 6th weeks after cell injection, ectopic bones were observed in muscles of nude mice of Group 1. Only fibrous tissue or a little bone was found in other two groups. CONCLUSIONS: BMP-2 gene transfected MSCs can differentiate into osteoblasts in vitro and induce bone formation in vivo.

An alternative subspace approach to EEG dipole source localization.

In the present study, we investigate a new approach to electroencephalography (EEG) three-dimensional (3D) dipole source localization by using a non-recursive subspace algorithm called FINES. In estimating source dipole locations, the present approach employs projections onto a subspace spanned by a small set of particular vectors (FINES vector set) in the estimated noise-only subspace instead of the entire estimated noise-only subspace in the case of classic MUSIC. The subspace spanned by this vector set is, in the sense of principal angle, closest to the subspace spanned by the array manifold associated with a particular brain region. By incorporating knowledge of the array manifold in identifying FINES vector sets in the estimated noise-only subspace for different brain regions, the present approach is able to estimate sources with enhanced accuracy and spatial resolution, thus enhancing the capability of resolving closely spaced sources and reducing estimation errors. The present computer simulations show, in EEG 3D dipole source localization, that compared to classic MUSIC, FINES has (1) better resolvability of two closely spaced dipolar sources and (2) better estimation accuracy of source locations. In comparison with RAP-MUSIC, FINES' performance is also better for the cases studied when the noise level is high and/or correlations among dipole sources exist.

A UML profile for framework modeling.

The current standard Unified Modeling Language(UML) could not model framework flexibility and extendability adequately due to lack of appropriate constructs to distinguish framework hot-spots from kernel elements. A new UML profile that may customize UML for framework modeling was presented using the extension mechanisms of UML, providing a group of UML extensions to meet the needs of framework modeling. In this profile, the extended class diagrams and sequence diagrams were defined to straightforwardly identify the hot-spots and describe their instantiation restrictions. A transformation model based on design patterns was also put forward, such that the profile based framework design diagrams could be automatically mapped to the corresponding implementation diagrams. It was proved that the presented profile makes framework modeling more straightforwardly and therefore easier to understand and instantiate.