Small interfering RNA (siRNA) is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA. siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases. However, the naked or unmodified siRNA has poor stability, easy to degrade by nuclease, short half-life, and low intracellular delivery. As an emerging non-viral nucleic acid delivery system, ionizable lipid nanoparticles play an important role in improving the druggability of siRNA. At present, one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease. This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery, focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNA-mediated gene silencing, which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.

To explore the influence of matrix materials in complicate ingredients on traditional Chinese medicine and investigate the excipients selection model based on balanced release characteristics of multicomponents, the influence of HPMC (K4M, K15M, K100M) and Carbomer (934P, 971P, 974P) was illustrated by testing in vitro release of ginsenoside-Rg1, ginsenoside-Rb1 and notoginsenoside-R1 in Panax notoginseng saponins (model drug, PNS). According to in vitro release results of PNS matrix tablets in water and artificial intestinal juice, the release curves were analyzed with Peppas equation and simulating factor (f). Significant differences in k value and n value among ginsenoside-Rg1, ginsenoside-Rb1 and notoginsenoside-R1 existed in various formulations. The release behaviors from various excipients could be described with Non-Fickian transport or super Case II transport pattern. The f2 values for ginsenoside-Rg1, ginsenoside-Rb1 and notoginsenoside-R1 in 971P matrix tablet containing 30% Carbomer 971P were 74.91, 53.45, 57.89 in water and 79.35, 55.51, 51.89 in artificial intestinal juice, respectively. The release profiles fit for the regulation of FDA. The result revealed that the balanced release rates of Rg1, Rb1 and R1 in 971P matrix tablet were obtained.
Acrylates ; chemistry ; Acrylic Resins ; chemistry ; Delayed-Action Preparations ; Excipients ; chemistry ; Ginsenosides ; isolation & purification ; pharmacokinetics ; Lactose ; analogs & derivatives ; chemistry ; Methylcellulose ; analogs & derivatives ; chemistry ; Panax notoginseng ; chemistry ; Plants, Medicinal ; chemistry ; Saponins ; administration & dosage ; isolation & purification ; pharmacokinetics ; Tablets

To reveal the characterization of interaction between Chinese and western medicinal injections, isothermal titration calorimetry (ITC) was applied to evaluating the interaction of Yiqi Fumai injection (YQFM, as mode drug) with epinephrine hydrochloride injection (YS) and 5% glucose injection (5% GS). The diversification of Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) were determined to judge the reaction types of colliquefaction procedures of different injections. Meanwhile, the fingerprints of YQFM before and after combined with the various injections were compared to validate the results. This work demonstrated that during the titration procedure of YQFM and YS, [ΔH] > T [ΔS] , that was to say the reaction was enthalpy-driving. And the reactive profile indicated that a great deal of heat gave out during the procedure. Obviously, chemical reactions happened and the internal component changed. On the other side, the reaction of YQFM combined with 5% GS was entropy-driving, because [ΔH] < T [ΔS]. The reactive profile showed there was only a little heat released. So non-chemical reactions happened and the major ingredients did not change. ITC could be applied to the evaluation on compatibility of other kinds of Chinese and western medicinal injection combination.
Calorimetry ; Drug Interactions ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Entropy ; Epinephrine ; chemistry ; pharmacology ; Glucose ; chemistry ; pharmacology ; Injections ; Thermodynamics

Objective To explore the association between ambient average temperature and hospital emergency room visits for cardiovascular diseases(International Classification of Diseases,Tenth Vision ICD-10:I00-I99) in Beijing,China.Methods Data was collected on daily hospital emergency room visits for cardiovascular diseases from Peking University Third Hospital,including meteorological data(daily average temperature,relative humidity,wind speed,and atmospheric pressure) from the China Meteorological Data Sharing Service System,and on air pollution from the Beijing Municipal Environmental Monitoring Center.Time-stratified case-crossover design was used to analyze data on 4 seasolls.Results After adjusting data on air pollution,1 degree(℃) increase of ambient average temperature would associate with the emergency room visits of odds ratio(Ors)as 1.282(95%CI:1.250-1.315).1.027(95%CI:1.001-1.055),0.661(95%CI:0.637-0.687),and 0.960 (95%CI:0.937-0.984) in spring,summer,autumn,and winter respectively.After controlling the influence of relative humidity,wind speed,and atmospheric pressure,1℃ increase in the ambient average temperature would be associated with the emergency room visits on Ors value as 1.423 (95%CI:1.377-1.471).1.082(95%CI:1.041-1.124),0.633(95%CI:0.607-0.660)and 0.971(95%CI:0.944-1.000) in spring,summer,auttmm,and winter respectively.Conclusion These data on outcomes suggested that the elevated level of ambient temperature would increase the hospital emergeney room visits for cardiovascular diseases in spring and summer while the elevated level of ambient temperature would decrease the hospital emergency room visits for the cardiovascular diseases in autumn and winter,suggesting that patients with cardiovascular diseases should pay attention to the climate change.

Objective To improve objectivity and accuracy of the diagnosis,prognosis,treatment efficiency and observe the levels of cognitive and intelligent deficits of children with attention deficit hyperactive disorder(ADHD).Methods Event related potentials(ERP)P3 wave test provocated by audition and Wechsler intelligence scale for children(C-WISC) test were detected and compared in 60 children with ADHD(ADHD group) and 60 cases of healthy children(healthy control group).The ERP P3 wave test results between 2 groups of children which had different intelligent balance ability were also compared.Results Compared with the healthy control group,there was a significantly longer latency of P3 wave(P

Objective To investigate the effects of gonadotropin releasing hormone agonist (GnRH- a) and antagonist (GnRH-ant) on cyclophosphamide (CTX)-induced ovarian damage in rats.Methods Seventy-two Sprague-Dawley female rats were divided randomly into six groups,which received normal saline (NS),CTX,GnRH-a+NS,GnRH-a+CTX,GnRH-ant+NS,and GnRH-ant+CTX respectively.Levels of serum follicle-stimulating hormone (FSH),luteinizing hormone (LH) and estradiol (E_2) were measured successively by the enzyme-linked immunosorbent assay method,and half of the rats were killed in the first week and between the fourth and the fifth week after stop of medication,respectively to compare the weight of the ovaries and the number of the primordial follicles and the growth follicles.Results (1) Throughout experiment,the serum levels of FSH,LH and E_2 of the control group fluctuated slightly,while those in the CTX group kept rising.During medication treatment,compared with the control group[(118?16) ?g/L, (350?35) ?g/L] and the CTX group[(113?15) ?g/L,(289?42) ?g/L],the concentrations of LH [(42 ?8)-(47?7) ?g/L,(31?5)-(36?7) ?g/L] and FSH [(124?45)-(136?32)?g/L,(178 ?54)-(198+27)?g/L] in the GnRH-a groups and the GnRH-ant groups were maintained at low levels significantly and the levels of LH in the GnRH-ant groups were significantly lower than that in the GnRH-a groups,but the levels of FSH in the GnRH-ant groups were significantly higher than that in the GnRH-a groups(P0.05),but the levels of FSH,LH and E_2 of the GnRH-ant+CTX group rose obviously and were similar to the levels of the CTX group,especially the FSH,and the levels of LH and FSH of the GnRH- ant + CTX group [(156?12) ?g/L,(520?44) ?g/L] and the CTX group [(178?18) ?g/L,(546?36) ?g/L] were significantly higher than that of the other four groups [(121?15)-(132?13) ?g/L,(335 ?35)-(359?26) ?g/L] at the 4~(th)-5~(th) week after stop of treatment(P0.05),but the number of all kinds of follicles declined significantly in the GnRH-ant+CTX group[(195?15),(36?12)] and the CTX group [(212?11),(36?9)] compared to the other four groups[(302?15)-(690?43),(44?12)-(58?11),P

OBJECTIVETo evaluate the impact of recombinant human growth hormone (rhGH) combined with hypocaloric nutrition on nitrogen balance and blood glucose in patients after gastrointestinal operation.

METHODSForty-eight patients undergone abdominal operations were randomly divided into either subcutaneous rhGH (0.15 IU/kg) or placebo (menstruum) injection daily for 7 days postoperatively. These two groups had similar nutritional intakes. Body weight, blood cell count, liver and renal function, plasma albumin, prealbumin, transferrin and fibronectin were measured at day 1 before operation as baseline and day 3 and day 10 after operation by standard laboratory techniques. Nitrogen balance and blood glucose were measured from day 3 to day 9 after operation.

RESULTSAt postoperative day 10, the cumulative nitrogen balance and the level of plasma fibronectin were significantly higher in rhGH group [13.21 g,(104.77+/-19.94) mg/L] than those in placebo group [-6.88 g, (93.03+/-16.03) mg/L] (P<0.05). Furthermore, at day 4 and from day 6 to day 9 after operation, daily nitrogen balance was higher in rhGH group than that in control group (P<0.05). Mean blood glucose level was significantly higher in rhGH group from day 3 to day 6 after operation [(7.68+/-2.15) vs (5.95+/-2.34) mmol/L, P<0.05]. But hyperglycemia could be controlled well by insulin treatment.

CONCLUSIONGrowth hormone combined with hypocaloric nutrition is effective and safe in promoting positive nitrogen balance and protein synthesis in post-operative patients, which is also beneficial to the improvement of nutritional status and prognosis.

Adult ; Aged ; Blood Glucose ; metabolism ; Caloric Restriction ; Digestive System Surgical Procedures ; Female ; Human Growth Hormone ; therapeutic use ; Humans ; Male ; Middle Aged ; Nitrogen ; metabolism ; Nutritional Support ; methods ; Postoperative Period ; Recombinant Proteins ; therapeutic use

OBJECTIVETo study the clinical, radiologic and pathologic features of solitary plasmacytoma of spine.

METHODSThe clinical, radiologic and pathologic features, as well as treatment and follow-up data, of 13 solitary plasmacytoma of spine cases were retrieved and analyzed. Immunohistochemical study using EnVision method for LCA, CD19, CD20, CD79a, CD3, CD7, PC, MUM1, CD138, IgG, IgM, kappa, lambda and Ki-67 was carried out.

RESULTSAll the tumours were primarily located in the vertebrae (including 9 cases in thoracic vertebrae and 4 cases in lumbar vertebrae). The male-to-female ratio was 3.3:1. The age of the patients ranged from 42 to 69 years (mean age = 56 years). The commonest symptom was pain in the surrounding regions. The degree of neurologic disturbance mostly depended on the extent of vertebral destruction and structural instability of the spine. Radiologic examination showed mainly osteolytic lesions in vertebrae. Magnetic resonance imaging demonstrated the presence of heterogeneous intensity inside the involved vertebrae (low in T1 weighted and high in T2 weighted images). Histologic examination showed diffuse infiltration by malignant cells. In well-differentiated plasmacytomas, the tumor cells resembled normal plasma cells. In poorly differentiated examples, the cellular morphology mimicked that of the centroblasts. The interstitial stroma was scanty and contained plenty of vessels, sometimes with formation of blood lakes. Amyloid deposition was present in some of the cases. Immunohistochemical study showed that the tumor cells were positive for CD79a and negative for CD20. Light chain restriction was detected in all the 13 cases studied. Plasma cell marker PC was expressed in all cases, while IgG was positive in 5 cases, IgM in 1 case, MUM1 in 10 cases and CD138 in 8 cases. Ki-67 index varied from 10% to 50%. All cases were operated, with adjuvant chemotherapy and radiotherapy given.

CONCLUSIONSCorrelation of clinical, radiologic and pathologic features is important in diagnosis of solitary plasmacytoma of spine. The possibility of multiple myeloma needs to be excluded. Early detection by radiologic examination, local surgical resection, post-operative chemoradiotherapy and long-term follow-up are prudent for successful management of this condition.

Adult ; Aged ; CD79 Antigens ; metabolism ; Chemotherapy, Adjuvant ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Lumbar Vertebrae ; Lymphoma, Large B-Cell, Diffuse ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Osteosarcoma ; pathology ; Plasmacytoma ; diagnosis ; metabolism ; pathology ; surgery ; Radiotherapy, Adjuvant ; Spinal Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Thoracic Vertebrae ; Tomography, X-Ray Computed

OBJECTIVETo evaluate the effect of short-term intensive therapy on blood glucose control, BETA-cell function, and blood lipid levels in newly diagnosed type 2 diabetic patients.

METHODSOut-patients with newly diagnosed type 2 diabetic patients were enrolled for intensive treatment with sulfonylureas and metformin for 12 weeks, and the therapeutic effect was evaluated.

RESULTSAfter the intensive treatment, FPG, 2 hPG, and HbA1c decreased significantly (P<0.01); HOMA-IR decreased and HOMA-B increased significantly (P<0.01), and TG, CHOL, LDL decreased significantly (P<0.01) after the treatment.

CONCLUSIONShort-term intensive treatment with glimepiride combined with metformin is safe and effective in newly diagnosed type 2 diabetic patients with HbA1c>9%.

Diabetes Mellitus, Type 2 ; drug therapy ; Drug Therapy, Combination ; Female ; Humans ; Male ; Metformin ; therapeutic use ; Sulfonylurea Compounds ; therapeutic use ; Treatment Outcome

OBJECTIVETo study the feasibility of osteogenic phenotype expression by human skin fibroblasts induced in polyglycolic acid (PGA) foams and the effect of tumor necrosis factor-alpha (TNF-alpha) on the expression of bone morphogenetic protein (BMP) receptors.

METHODSThe fibroblasts were isolated, purified from human skin. (1) Fibroblasts were seeded onto PGA foams. The cell-PGA complexes were cultured in RCCS for 6 weeks, in the media of TNF-alpha (50 U/ml) and BMP-2 (0.1 microg/ml). 1 d, 3 and 6 weeks later, cells and extracellular matrix were investigated by electron microscopic and histochemistry observation respectively. Secretion of osteogenic markers were analyzed by biochemical methods. (2) Fibroblasts were seeded on the glass fragments or culture flasks and treated with TNF-alpha (50 U/ml) in different usage (one-time, all-time). The RT-PCR method and the immunohistochemistry fluorescence staining were used to examine the influence of TNF-alpha on the mRNA expression and the protein expression of the type I BMP receptors at 2, 4, 6, 8 d after treatment.

RESULTSFibroblasts seeded on the PGA foams formed 3-dimensional matrix 3 weeks after seeding, which was demonstrated as osteo-tissue by tetracycline labeling and ARS staining. Cells secreted much more bone-specific alkaline phosphatase (B-AKP) and osteocalcin (OCN) into supernatant than the cells that were cultured in the media without TNF-a and BMP2. Eight days after all-time usage, the TNF-alpha (50 U/ml) increased the expression of the mRNA and protein of the type IB BMP receptor.

CONCLUSIONSFibroblasts on 3-D cell-foam structures can express osteoblastic phenotype under certain inducing conditions. The numerous fibroblasts in body would be a promising resource for cell seeds candidate of tissue- engineered bone. TNF-alpha provides the essential condition for BMP2's target effect on fibroblasts, and combined use of TNF-alpha and BMP2 is one of the regulating factors.

Bone Morphogenetic Protein 2 ; Bone Morphogenetic Protein Receptors, Type I ; biosynthesis ; genetics ; Bone Morphogenetic Protein Receptors, Type II ; biosynthesis ; genetics ; Bone Morphogenetic Proteins ; pharmacology ; Cell Culture Techniques ; methods ; Cell Differentiation ; drug effects ; Cells, Cultured ; Drug Synergism ; Fibroblasts ; cytology ; drug effects ; metabolism ; Humans ; Phenotype ; Polyglycolic Acid ; Transforming Growth Factor beta ; pharmacology ; Tumor Necrosis Factor-alpha ; pharmacology