Identification of Human Serum Protein Targets of Qianggu Decoction(强骨饮) in Primary Type Ⅰ Osteoporosis Based on Tandem Mass Tag Labeling and Liquid Chromatography-Tandem Mass Spectrometry Technology

Objective： To investigate the serum protein targets of Qianggu Decoction（强骨饮, QGD） on treating osteoporosis by the proteomics analysis using tandem mass tag（TMT） and liquid chromatographytandem mass spectrometry（LC-MS/MS）. Methods： Twenty serum protein samples were recruited（10 patients with primary type Ⅰ osteoporosis before and after QGD treatment） and the high abundance ratios protein was removed, two serum samples were extracted and labeled with TMT reagent. Then, mass spectrometric detection, identification of differentially expressed proteins and bioinformatics analysis of differentially expressed proteins were carried out. Results： A total of 60 proteins were identified, within a 99% confidence interval, to be differentially regulated of which, 34 proteins were up-regulated and 26 proteins were down-regulated. Differentially expressed proteins analyzed by Gene Ontology（GO） annotation mainly get involved in 12 different biological processes, 7 types of cellular components, and 6 kinds of molecular functions. Angiotensinogen（AGT）, stromelysin-1（MMP3）, heparanase（HPSE） and glyceraldehyde-3-phosphate dehydrogenase（GAPDH） were screened as candidate protein targets of QGD treatment, which were related to metabolic mechanism of bone remodeling and/or bone collagen of osteoporosis. By the utilization of the protein-protein interaction network analysis tool named STRING10.0, it showed that AGT, MMP3, HPSE and GAPDH were located in the key node of the protein-protein interactions network. Furthermore, AGT, MMP3, HPSE and GAPDH were found to be directly related to BMP, MAPK, Wnt, SMAD and tumor necrosis factor ligand superfamily member 11（TNFSF11） families. Conclusions： The proteomics analysis by using TMT combined with LC-MS/MS was a feasible method for screening the potential therapeutic targets associated with QGD treatment. It suggests that AGT, MMP3, HPSE and GAPDH may be candidate protein targets of QGD treatment which can be used as therapeutic effect monitor and early diagnosis of primary type Ⅰ osteoporosis.

Polycytosine RNA-binding protein 1 regulates osteoblast function via a ferroptosis pathway in type 2 diabetic osteoporosis

BACKGROUND Recently,type 2 diabetic osteoporosis(T2DOP)has become a research hotspot for the complications of diabetes,but the specific mechanism of its occurrence and development remains unknown.Ferroptosis caused by iron overload is con-sidered an important cause of T2DOP.Polycytosine RNA-binding protein 1(PCBP1),an iron ion chaperone,is considered a protector of ferroptosis.AIM To investigate the existence of ferroptosis and specific role of PCBP1 in the development of type 2 diabetes.METHODS A cell counting kit-8 assay was used to detect changes in osteoblast viability under high glucose(HG)and/or ferroptosis inhibitors at different concentrations and times.Transmission electron microscopy was used to examine the morpho-logical changes in the mitochondria of osteoblasts under HG,and western blotting was used to detect the expression levels of PCBP1,ferritin,and the ferroptosis-related protein glutathione peroxidase 4(GPX4).A lentivirus silenced and overex-pressed PCBP1.Western blotting was used to detect the expression levels of the osteoblast functional proteins osteoprotegerin(OPG)and osteocalcin(OCN),whereas flow cytometry was used to detect changes in reactive oxygen species(ROS)levels in each group.RESULTS Under HG,the viability of osteoblasts was considerably decreased,the number of mitochondria undergoing atrophy was considerably increased,PCBP1 and ferritin expression levels were increased,and GPX4 expression was decreased.Western blotting results demonstrated that infection with lentivirus overexpressing PCBP1,increased the expression levels of ferritin,GPX4,OPG,and OCN,compared with the HG group.Flow cytometry results showed a reduction in ROS,and an opposite result was obtained after silencing PCBP1.CONCLUSION PCBP1 may protect osteoblasts and reduce the harm caused by ferroptosis by promoting ferritin expression under a HG environment.Moreover,PCBP1 may be a potential therapeutic target for T2DOP.

Update on type 2 diabetes-related osteoporosis

It was previously understood that body weight gain and obesity observed in type 2 diabetes mellitus(T2DM) could be beneficial since body weight increase elevated bone mineral density and thus helped maintain the skeletal framework.However,a number of recent findings in humans and rodents have revealed that T2 DM is not only associated with trabecular defects but also increases cortical porosity,and compromised bone cell function and bone mechanical properties.Hyperglycemia and insulin resistance in T2 DM may further induce osteoblast apoptosis and uncoupling bone turnover.Prolonged accumulation of advanced glycation end products and diminished activity of lysyl oxidase,an essential enzyme for collagen cross-link,can lead to structural abnormalities of bone collagen fibrils,brittle matrix,and fragility fractures.Our studies in T2 DM rats showed that dyslipidemia,which often occurs in T2 DM,could obscure the T2DM-associated changes in bone microstructure and osteopenia.Longitudinal bone growth regulated by the growth plate chondrocytes is also impaired by T2 DM since differentiation of growth plate chondrocytes is arrested and retained in the resting state while only a small number of cells undergo hypertrophic differentiation.Such a delayed chondrocyte differentiation may have also resulted from premature apoptosis of the growth plate chondrocytes.Nevertheless,the underlying cellular and molecular mechanisms of insulin resistance in osteoblasts,osteoclasts,osteocytes,and growth plate chondrocytes remain to be investigated.

Insulin-Like Growth Factor-1 and Osteocalcin Are Correlated with Markers of Osteoporosis in Postmenopausal Women with Type-2 Diabetes

Objective: The study was conducted to evaluate the relation between insulin-like growth factor-1 and osteocalcin and markers of bone modulation (osteoprotegerin;OPG, receptor activator nuclear kappa B;RANK and RANK ligand;RANKL) in postmenopausal Type 2 diabetic women with and without osteoporosis. Methods: The study was conducted on 90 female divided into three groups (30 each). Group I included healthy postmenopausal women as a control, Group II included diabetic postmenopausal women without osteoporosis Group III included diabetic postmenopausal women with osteoporosis. Fasting blood samples were obtained for the determination of blood glucose, HbA1c, total and ionized calcium, OPG, RANK and RANKL. Also the levels of IGF-1 and osteocalcin were assessed. Results: In postmenopausal Type 2 diabetic women, the osteoporosis resulted in derangement in OPG/sRANKL system. The serum level of OPG was elevated while sRANKL declines in osteoporotic postmenopausal Type 2 diabetic women. IGF-1 level decreased in diabetic postmenopausal women but those women with osteoporosis showed a great decline by about 60%. IGF-1 level in osteoporotic diabetic postmenopausal women was correlated with BMD and most bone turnover markers (OPG, sRANKL, OPG/sRANKL). Osteocalcin declined significantly only in those women with osteoporosis not without osteoporosis. Conclusions: The circulating levels of OPG and sRANKL were not useful markers for bone status in postmenopausal women while the circulating levels of IGF-1 and osteocalcin might give useful information about bone status in postmenopausal diabetic women.

To Explore the Relationship between Lower Extremity Vascular Sclerosis and Osteoporosis in Elderly Men with Type 2 Diabetes Mellitus

Objective: To investigate the correlation between lower extremity vascular sclerosis and osteoporosis in elderly men with type 2 diabetes mellitus. Methods: A total of 359 elderly male patients with type II diabetes hospitalized in the First Affiliated Hospital of Chongqing Medical University from January 2018 to June 2023 were retrospectively collected. According to the BMD (Bone Density Value), the patients were categorized into osteoporotic (T ≤ -2.5, n = 248) and non-osteoporotic groups (T > -2.5, n = 111). T test and Chi-square test were used to evaluate the differences in clinical data, biochemical markers and ABI between two groups. Multivariate logistic regression was used to analyze the risk factors of osteoporosis in elderly men with type 2 diabetes mellitus. Results: Compared with the non-osteoporotic group, the differences in diabetes course, systolic blood pressure, ABI, BMI, uric acid, triglyceride, and HDL in the osteoporotic group were statistically significant (P < 0.05). Logistic multivariate regression analysis showed that lower extremity vascular sclerosis was an independent risk factor for osteoporosis in elderly men with type 2 diabetes mellitus (P Conclusion: Atherosclerosis of the lower extremities in elderly men with T2DM is closely related to osteoporosis, and can lead to a decrease in bone mass, and an increase in osteoporosis.

Relationship between DEXA bone mineral density measurement results and serum cytokines as well as insulin resistance in patients with type 2 diabetes mellitus and osteoporosis

Objective:To study the relationship between DEXA bone mineral density measurement results and serum cytokines as well as insulin resistance in patients with type 2 diabetes mellitus and osteoporosis.Methods:Patients newly diagnosed with type 2 diabetes were selected and divided into normal bone mass group, osteopenia group and osteoporosis group according to the DEXA femoral neck bone mineral density measurement results, the bone mineral density of all parts in of three groups of patients were measured, and serum was collected to determine the levels of bone metabolism indexes, cytokines and insulin.Results:Femoral trochanter, Ward's area as well as the 2-4th lumbar vertebra bone mineral density values of osteopenia group and osteoporosis group were significantly lower than those of normal bone mass group, and the femoral trochanter, Ward's area as well as the 2-4th lumbar vertebra bone mineral density values of osteoporosis group were significantly lower than those of osteopenia group;serum N-MID, PINP and BGP levels of osteopenia group and osteoporosis group were significantly lower than those of normal bone mass group whileβ-CTX, TRACP5b, Ins, Chemerin, TNF-α, IL-1β and MCP-1 levels were significantly higher than those of normal bone mass group;serum N-MID, PINP and BGP levels of osteoporosis group were significantly lower than those of osteopenia group whileβ-CTX, TRACP5b, Ins, Chemerin, TNF-α, IL-1β and MCP-1 levels were significantly higher than those of osteopenia group;serum Ins, Chemerin, TNF-α, IL-1β and MCP-1 levels were negatively correlated with N-MID, PIN and BGP levels, and positively correlated with serumβ-CTX and TRACP5b levels.Conclusion:Excessively synthesized inflammatory factors and compensatory hyperinsulinemia in patients with type 2 diabetes mellitus and osteoporosis can promote bone resorption and inhibit bone formation, thus resulting in the osteopenia in multiple areas of the body.

氧化苦参碱对皮肤创面愈合中PCNA、α-SMA及Type Ⅰ collagen的影响

目的探讨氧化苦参碱对小鼠皮肤创面愈合中血清增殖细胞核抗原(PCNA)、α-平滑肌肌动蛋白(α-SMA)及细胞Ⅰ型胶原蛋白(Type Ⅰ collagen)的影响。方法昆明小鼠背部手术制备1.5 cm×1.5 cm全层皮肤缺损创面模型。自第1 d始,除对照组给予等量生理盐水外,余各组分别按20、40、80 mg/kg给予氧化苦参碱。Van Gieson纤维胶原染色法观察小鼠背部皮肤创面组织胶原纤维的表达;免疫组学法评价创面组织中PCNA、α-SMA及Type Ⅰ collagen的表达。结果Van Gieson纤维胶原染色显示,氧化苦参碱可促进新生肉芽组织、毛细血管及新生纤维胶原生长。免疫组学研究显示,在第7 d时,氧化苦参碱20、40、80 mg/kg使小鼠皮肤创面组织中PCNA表达明显升高(P<0.05);在第9 d、11 d时,氧化苦参碱20 mg/kg使小鼠皮肤创面组织中α-SMA显著增加;氧化苦参碱20 mg/kg在第3 d、11 d,氧化苦参碱40 mg/kg在第3 d,氧化苦参碱80 mg/kg在第3 d、7 d引起Type Ⅰ collagen的表达显著升高(P<0.05)。结论氧化苦参碱能增加皮肤创面愈合中PCNA、α-SMA及Type Ⅰ collagen的表达。

辽东兰花岭地区古元古代Ⅰ型花岗岩类与辽吉A型花岗岩对比研究

辽东半岛是华北克拉通胶-辽-吉古元古代活动带的重要组成部分,古元古代经历了复杂的构造演化过程,并记录了多期岩浆-变质作用,约2.2 Ga的辽吉A型花岗岩和1.89~1.85 Ga的巨斑状花岗岩、正长岩分别标志着辽东古元古代造山作用的开端和结束。最新研究显示,2.20~2.15 Ga的岩浆作用形成了2种不同类型的花岗岩,它们可能具有不同的岩石成因和构造意义。在青城子铅锌矿集区北部采集的兰花岭、白砬子花岗闪长岩和黄泊辉绿岩,锆石U-Pb年龄分别为2177±19 Ma、2129±36 Ma、1876±29 Ma。花岗闪长岩的岩石成因类型、地球化学特征与典型的约2.2 Ga的辽吉A型花岗岩明显不同,属于弱过铝质、低钾钙碱性—碱性岩石,Zr、Hf、Nb、Rb含量较低,K_(2)O/Na_(2)O值、稀土元素总量极低,为典型的Ⅰ型花岗岩类。根据锆石Lu-Hf同位素分析,ε_(Hf)(t)值为-5.1~9.0,二阶段Hf模式年龄t_(DM2)为2089~2817 Ma,岩浆源区为约2.5 Ga的太古宙地壳物质和少量软流圈地幔物质。兰花岭地区花岗闪长岩具备岛弧或活动大陆边缘的地球化学亲缘属性,可能形成于弧岩浆俯冲挤压环境;结合形成于伸展环境的A型条痕状花岗岩特征,认为约2.2 Ga辽东地区古元古代活动带呈现总体伸展、局部挤压的构造环境,为洋壳板块向龙岗地块俯冲碰撞过程中或碰撞后的弧后盆地。

Effects of Icariin on Expression of OPN mRNA and Type ⅠCollagen in Rat Osteoblasts in Vitro

To study the effects of Icariin on expression of osteopontin （OPN） mRNA and type Ⅰ collagen in rat osteoblasts in vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvaria of new-born new-born fetal Sprague-Dawley （SD） rats by means of modified sequential collagenase digestion and incubated in MEM medium and the cell morphology was observed under inverted phase contrast microscope, OB was identified by alkaline phosphatase （ALP） staining. Different concentration （0.1μg/mL, 1.0 μg/mL, 10 μ/mL） of Icariin was added to the OB and incubated. The effect of Icariin on the proliferation and osteogenesis of OB was monitored by MTT analysis. The expression of type l collagen was estimated with immunohistochemistry techniques. The expression levels of mRNA of OPN in the cells in every group were examined by reverse-transcriptase ploymerase chain reaction （RT-PCR）. The expression of OPN mRNA and type Ⅰ collagen was strengthened gradually with the increase of Icariin concentration and peaked with 10 μg/mL Icariin on the 5th day. Icariin could significantly promote the expression of OPN mRNA and type Ⅰ collagen in rat osteoblasts in vitro. The levels of expression of OPN mRNA and type Ⅰ collagen were changed with different concentration of Icariin. Icariin could effectively prevent and treat osteoporosis and promote the bone formation.

Osteoporosis and fractures in liver disease: Relevance, pathogenesis and therapeutic implications

It is being increasingly recognized that patients with liver disease develop bone loss that can be severe enough to lead to atraumatic fractures and thus markedly diminish life quality and expectancy. The estimated prevalence for liver-related osteoporosis is between 20-420/100000 of the general population, and fractures between 60-880/100000. It should be kept in mind that up to 40% of patients with chronic liver disease may experience a fracture. The pathogenic mediators include fibronectin, insulin like growth factor-I, and various cytokines, but decreased vitamin D and/or treatment with corticosteroids contribute to worsening bone health. Despite the advances in bone biology that have shed some light on the pathogenesis of this bone loss, treatment options remain nonspecific and tightly linked to treatments of other forms of osteoporosis. Thus, treatment should include calcium and vitamin D supplementation in all patients with chronic liver disease. Therapy with bisphosphonates should be considered, especially in patients receiving corticosteroids. This review focuses on the prevalence of this entity as well as the evidence available with regard to the pathogenesis of bone loss in liver disease, the diagnostic steps required in all patients, and the therapeutic options available.

Features and imbibition mechanisms of Winsor Ⅰ type surfactant solution in oil-wet porous media

The relationship between NaCl concentration and the phase change behavior of microemulsion of anionic surfactant was characterized by the salinity scan experiments.The wettability of WinsorⅠtype surfactant solution(WⅠsolution)and the effect of NaCL concentration on phase change behavior of WⅠsolution and imbibition in oil-wet porous media were investigated by microfluidic experiments in this study.The WⅠsolution and WinsorⅠtype microemulsion are similar in wetting phase with stronger wettability than other phases.Two main mechanisms of WⅠsolution enhancing imbibitions recovery in oil wet porous media are the wetting phase drive and residual oil solubilization.Under the salinity condition of WinsorⅠtype microemulsion,the NaCl concentration has strong impact on the imbibition mechanism of WⅠsolution,the higher the NaCl concentration,the complex the imbibition process and the higher the imbibition efficiency will be.The NaCl concentration has strong impact on the solubilization ability to oil of the WⅠsolution,the higher the NaCl concentration,the stronger the solubility of the WⅠsolution to residual oil will be.

TypeⅠinositol 1, 4, 5-triphosphate receptors increase in kidney of mice with fulminant hepatic failure

AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.

Lentinula edodes extract inhibits matrix metalloproteinase expression and increases typeⅠprocollagen expression via the p38 MAPK/c-Fos signaling pathway in ultraviolet A and B-irradiated HaCaT keratinocytes

Objective:To determine the effect of Lentinula edodes extract on ultraviolet(UV)A and UVB-induced changes in matrix metalloproteinase(MMP)and type I procollagen expression using human immortalized HaCaT keratinocytes.Methods:Lentinula edodes ethanol extract(LEE)was obtained by extraction with 80%ethanol for 4 h at 80℃.Effect of LEE on UVinduced alteration on the expression and production of MMPs and type I procollagen in keratinocytes was investigated using ELISA,RT-PCR,and Western blotting assay.To determine the underlying mechanism of LEE-mediated effects,mitogen-activated protein kinase(MAPK)and activator protein 1 signaling pathways were analysed by Western blotting assay.Results:LEE significantly inhibited the expression of MMP-1 and MMP-9 and increased the expression of type I procollagen in UVA and UVB-irradiated HaCaT keratinocytes.The phosphorylation levels of p38 were significantly inhibited by LEE whereas it did not affect c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation.Suppression of p38 phosphorylation was also accompanied by downregulation of UVA and UVB-induced increase in c-Fos.Conclusions:LEE effectively inhibits the expression of MMP-1 and MMP-9 and increases type I procollagen production through the p38 MAPK/c-Fos signaling pathway in UVA and UVB-irradiated HaCaT keratinocytes.This findings suggest that Lentinula edodes may be developed as a cosmetic material to suppress UV exposuremediated skin aging.

Synthesis and high temperature thermoelectric transport properties of Si-based type-Ⅰ clathrates

N-type Si-based type-Ⅰ clathrates with different Ga content were synthesized by combining the solid-state reaction method,melting method and spark plasma sintering （SPS） method.The effects of Ga composition on high temperature thermoelectric transport properties were investigated.The results show that at room temperature,the carrier concentration decreases, while the carrier mobility increases slightly with increasing Ga content.The Seebeck coefficient increases with increasing Ga content. Among all the samples,Ba7.93Ga17.13Si28.72exhibits higher Seebeck coefficient than the others and reaches -135μV·K^-1 at 1000 K.The sample prepared by this method exhibits very high electrical conductivity,and reaches 1.95x 10^5 S·m^-1 for Ba8.01Ga16.61Si28.93 at room temperature.The thermal conductivity of all samples is almost temperature independent in the temperature range of 300-1000 K,indicating the behaviour of a typical metal.The maximum ZT value of 0.75 is obtained at 1000 K for the compound Ba7.93Ga17.13Si28.72.

Novel electrospun poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits for repair of peripheral nerve injury

Recent studies have shown the potential of artificially synthesized conduits in the repair of peripheral nerve injury. Natural biopolymers have received much attention because of their biocompatibility. To investigate the effects of novel electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits(biopolymer nanofiber conduits) on the repair of peripheral nerve injury, we bridged 10-mm-long sciatic nerve defects with electrospun absorbable biopolymer nanofiber conduits, poly(ε-caprolactone) or silicone conduits in Sprague-Dawley rats. Rat neurologica1 function was weekly evaluated using sciatic function index within8 weeks after repair. Eight weeks after repair, sciatic nerve myelin sheaths and axon morphology were observed by osmium tetroxide staining, hematoxylin-eosin staining, and transmission electron microscopy.S-100(Schwann cell marker) and CD4(inflammatory marker) immunoreactivities in sciatic nerve were detected by immunohistochemistry. In rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits, no serious inflammatory reactions were observed in rat hind limbs, the morphology of myelin sheaths in the injured sciatic nerve was close to normal. CD4 immunoreactivity was obviously weaker in rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits than in those subjected to repair with poly(ε-caprolactone) or silicone. Rats subjected to repair with electrospun absorbable biopolymer nanofiber conduits tended to have greater sciatic nerve function recovery than those receiving poly(ε-caprolactone) or silicone repair. These results suggest that electrospun absorbable poly(ε-caprolactone)/type Ⅰ collagen nanofiber conduits have the potential of repairing sciatic nerve defects and exhibit good biocompatibility. All experimental procedures were approved by Institutional Animal Care and Use Committee of Taichung Veteran General Hospital, Taiwan, China(La-1031218) on October 2, 2014.

一类广义Type Ⅰ函数的多目标优化问题

对于非光滑多目标优化的模型,定义了几种广义Type Ⅰ函数,研究了广义Type Ⅰ函数的多目标优化问题,得到了有效解的最优性条件.

Type Ⅰ kerogen-rich oil shale from the Democratic Republic of the Congo: mineralogical description and pyrolysis kinetics

The Democratic Republic of the Congo holds important reserves of oil shale which is still under geological status.Herein,the characterization and pyrolysis kinetics of typeⅠkerogen-rich oil shale of the western Central Kongo(CK)were investigated.X-ray diffraction,Fourier-transform infrared spectroscopy and thermal analysis(TG/DTA)showed that CK oil shale exhibits a siliceous mineral matrix with a consistent organic matter rich in aliphatic chains.The pyrolysis behavior of kerogen revealed the presence of a single mass loss between 300 and 550°C,estimated at 12.5%and attributed to the oil production stage.Non-isothermal kinetics was performed by determining the activation energy using the iterative isoconversional model-free methods and exhibits a constant value with E=211.5±4.7 kJ mol.1.The most probable kinetic model describing the kerogen pyrolysis mechanism was obtained using the Coats–Redfern and Arrhenius plot methods.The results showed a unique kinetic triplet confirming the nature of kerogen,predominantly typeⅠand reinforcing the previously reported geochemical characteristics of the CK oil shale.Besides,the calculation of thermodynamic parameters(ΔH~*,ΔS~*andΔG~*)corresponding to the pyrolysis of typeⅠkerogen revealed that the process is non-spontaneous,in agreement with DTA experiments.

Type Ⅰ neurofibromatosis with spindle cell sarcoma: A case report

BACKGROUND Neurofibromatosis type Ⅰ(NF1) is the most frequent subtype of neurofibromatosis. Its related tumor-suppressor syndromes are characterized by a predisposition to multiple tumor types and other disorder presentations. In addition, the incidence of tumors is much higher in patients with neurofibromatosis type Ⅰ. However, there are very few reports at home and abroad on this topic. Here, we present a case of NF1 with spindle cell sarcoma.CASE SUMMARY A 50-year-old male was found to have a right axillary mass for 20 years.Specialist examination found cafe-au-lait spots on many parts of the skin,rounded nodules in the skin, a bulge in the right armpit, touching a lump(10 cm× 6 cm, hard, unclear boundary, poor mobility, local tenderness). The anterior side of the thigh felt weakened on the opposite side;in the right groin a swollen lymph node(hard, clear border, good mobility, local tenderness). According to the results of positron emission tomography/computed tomography, puncture pathology and immunohistochemistry, genetic testing, a diagnosis of NF1 with spindle cell sarcoma was confirmed. According to the genetic testing result, the patient was given a targeted treatment with crizotinib.CONCLUSION Surgery, chemotherapy and radiotherapy are the main treatment methods of NF1. However, with the continuous progress of molecular biology research,molecular targeted therapy may bring benefits for patients.

Significance of elevated serum concentration of type Ⅰ collagen metabolites and its correlation with serum interleukin 6 activities in multiple myeloma

In this study, serum concentrations of carboxyterminal propeptide of type Ⅰ collagen(PICP) and carboxyterminal cross-linked telopeptide of type Ⅰ collagen (ICTP), which represent the rates of synthesis and degradation of type Ⅰ collagen, were determined by radioimmunoassay in 56 patients with multiple myeloma (MM) and 22 healthy controls. It was discovered that serum concentrations of both PICP and ICTP were higher in MM than those in healthy controls (P<0. 01 ). With the disease progressing and the number of bone lesions increasing,serum concentration of ICTP elevated while serum concentration of PICP showed no significant change. Neither serum PICP nor ICTP concentration was related to M-component classes. Our results indicated that serum ICTP concentration was a good serological marker to reflect severity of bone lesions in MM and elevated serum PICP concentration might be due to compensatory increase in type Ⅰ collagen synthesis. Moreover, we also found that serum ICTP concentrations in MM correlated with serum interleukin-6 (IL-6) activities (r= 0. 610, P< 0. 01),which confirms the effectiveness of IL-6 as an osteoclast activating factor.

Protein Flexibility and Multiple Docking in Ligand Docking and Virtual Screening to the BRAF(TypeⅠ1/2)Inhibitors

BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug design（CADD）. Appropriate protein conformation and docking method are essential for the successful virtual screening experiments. One approach considering protein flexibility and multiple docking methods was proposed in this study. Six DFG-in/αC-helix-out crystal structures of BRAF, three docking programs（Glide, GOLD and Ligand Fit） and 12 scoring functions were applied for the best combination by judging from the results of pose prediction and retrospective virtual screening（VS）. The most accurate results（mean RMSD of about 0.6 A） of pose prediction were obtained with two complex structures（PDB： 3 C4 C and 3 SKC） using Glide SP. From the retrospective VS, the most active compounds were identified by using the complex structure of 3 SKC, indicated by a ROC/AUC score of 0.998 and an EF of 20.6 at 5% of the database screen with Glide-SP. On the whole, PDB 3 SKC could achieve a higher rate of correct reproduction, a better enrichment and more diverse compounds. A comparison of 3 SKC and the other X-ray crystal structures led to a rationale for the docking results. PDB 3 SKC could achieve a broad range of sulfonamide substitutions through an expanded hydrophobic pocket formed by a further shift of the αC-helix. Our study emphasized the necessity and significance of protein flexibility and scoring functions in both ligand docking and virtual screening.