With the development of natural products, the research activities on the solubilization methods of water-insoluble natural products have been carried out worldwide. Big molecular weight and poor solubility of most natural active ingredients lead to a very poor oral absorption and low bioavailability, which has extremely limited their development in pharmaceutical fields and clinical application. As a result, it is necessary to find out a suitable technique to improve the solubility and enhance the oral bioavailability of insoluble natural drugs. Based on the related references published in these years, this review introduced some new techniques to improve the solubility and bioavailability of natural drugs, including prodrugs, inclusion complex, solid dispersion, cocrystals, osmotic pump, liquisolid compacts, micronization, self-microemulsifying, nanosuspensions, lipsomes, polymeric micelles and so on, and summarized the theory, characteristics, application range, application examples, problems and development direction of each technique.
Administration, Oral ; Biological Availability ; Biological Products ; administration & dosage ; chemistry ; pharmacokinetics ; Chemistry, Pharmaceutical ; methods ; trends ; Solubility ; Technology, Pharmaceutical ; methods ; trends ; Water

The cell-free plasma DNA (cfpDNA) has been suggested as a useful tumor marker for its quantitative and qualitative tumor-specific alterations that reflect the biological characteristics and the progression and outcomes of tumors.Therefore,it has been used as liquid biopsy to detect cfpDNA in peripheral blood for the diagnosis,monitoring of clinical effects,and prognosis of malignancies

Objective To investigate the methods and results of lengthened proximal femoral nail antirotation (PFNA) in the treatment of femoral shaft fractures combined with ipsilateral femoral neck fractures. Methods Of the 21 patients with femoral shaft combined with ipsilateral femoral neck fractures treated by lengthened PFNA from 2006 to 2009,16 patients with complete follow-up were retrospectively studied.There were 15 males and 1 female,at mean age of 35 years (range,21-51 years).Injury causes were all high-energy trauma including traffic injuries in 11 patients and fall injuries in five.According to Garden classification,there were seven patients with type Ⅰ femoral neck fractures,six with type Ⅱ and three with type Ⅲ.Femoral shift fractures contained six superior part fractures and nine medial part fractures and one inferior part fracture.According to Winquist classification,there were two patients with type Ⅰ femoral shaft fractures,four with type Ⅱ,six with type Ⅲ and four with type Ⅳ.Two patients had open fractures belonging to type Ⅰ Gustilo-Anderson.Harris hip score was used to evaluate functional outcomes at the last follow-up postoperatively. Result The mean follow-up time was 2.4years (range,1-4 years ).The mean period for healing of femoral neck and shaft fractures was 4.2months ( range,3-6 months) and 5.1 months ( range,3-8 months) respectively.Four patients showed delayed diagnoses of femoral neck fractures ; two patients had delayed union of femoral shaft fractures ; one suffered from avascular necrosis of the femoral head ; one patient presented 3 cm of extension of the affected limb and was accompanied by active pain of the knee joint for over four months.According to Harris score,function of hip joints was excellent in seven patients,good in six and fair in three,with excellence rate of 82％. Conclusions It is relatively few that the femoral shaft fracture is combined with ipsilateral femoral neck fracture.The rate of missed diagnosis of femoral neck fractures is high and the patients with high energy trauma hould be highly paid attention to.Lengthened PFNA conforms to characteristics of biomechanical fixation and presents short operation time and solid fixation. Lengthened PFNA achieves affirmatory effects for treatment of femoral shaft fractures combined with ipsilateral femoral neck fractures.

BACKGROUND:About 10%-49%of maintenance hemodialysis patients are accompanied by refractory hypertension and common drug therapy is ineffective. Continuous renal replacement therapy could clear the middle and giant molecule toxins in the blood plasma of patients, it is theoretical y treat refractory hypertension through reducing the toxin levels.
OBJECTIVE:To observe the effect of continuous renal replacement therapy on maintenance hemodialysis patients with refractory hypertension.
METHODS:A total of 45 maintenance hemodialysis patients with refractory hypertension were randomly divided into two groups, hemodialysis group (n=22) and continuous blood purification group (n=23). Hemodialysis group underwent conventional hemodialysis treatment. Continuous blood purification group underwent conventional hemodialysis therapy, and treatment of continuous blood purification weekly.
RESULTS AND CONCLUSION:After 3 months of treatment, the renin activity, endothelin, angiotensin II, C-reactive protein, interleukin-6, and tumor necrosis factor-αlevels in continuous blood purification group were significantly lower than the levels before the experiment, while 24-hour mean blood pressure levels were significantly decreased (P<0.05). In hemodialysis group, renin activity, endothelin, angiotensin II, C-reactive
protein, interleukin-6, and tumor necrosis factor-αlevels and 24-hour mean blood pressure did not change (P>0.05). After the test, continuous blood purification group showed significantly lower levels of the above index than the hemodialysis group (P<0.05). Continuous renal replacement therapy plus hemodialysis significantly reduce the blood pressure in maintenance hemodialysis patients with refractory hypertension, the potential mechanisms are mediated by lowering the middle and giant molecule toxin as wel as inflammatory factor in plasma.

BACKGROUND: The full three-dimensional finite element model can not only establish a realistic three-dimensionalmodel, but also can simulate the osteotomy on the model. Analysis of biomechanics guides the clinical operation.OBJECTIVE: To establish a three-dimensional finite element model of ankylosing spondylitis kyphosis and provide an effective digital platform for further studies.METHODS: A 30-year-old male patient with ankylosing spondylitis kyphosis participated voluntarily in the current study. CTimages obtained from CT transverse scanning from C1 to the sacrococcyx were imported into Mimics 17.0 software toestablish a three-dimensional geometric model of the posterior spine. The geometric model was then imported into Studio Geomagic 2013 software. For the subsequent optimization of image processing, the posterior spine convex geometry wasestablished on the three-dimensional geometric model. We used Unigraphics NX 8.5 to establish the spinal kyphosis surfacemodel, then added modeling of calcification of the ligaments, partial resection of useless sacral bone, and finally, imported themodel into ANSYS 15.0 finite element analysis software, then added the ligaments and set the parameters of the material,generating a complete three-dimensional finite element model of ankylosing spondylitis.RESULTS AND CONCLUSION: A three-dimensional finite element model of complete ankylosing spondylitis wassuccessfully established. Using the ten-node approach, we generated 398370 tetrahedral elements, and 668538 nodes.This will provide a reliable digital platform for the next step of biomechanical analysis.

Objective To compare diagnostic performance of ultrasound and radionuclide imaging in diagnosis of Meckel's diverticulum.Methods Totally 46 children suspected with Meckel's diverticulum were enrolled.Ultrasound,radionuclide imaging data were analyzed and compared with pathology.Results In 46 children suspected with Meckel's diverticulum,38 cases were confirmed by operation.Thirty-three cases of 38 were diagnosed Meckel's diverticulum by ultrasound,5 cases of 38 were false negative,there was no false positive case.Radionuclide imaging was positive in 24 cases of 46,false positive in 4 eases and false negative in 18 cases.The ultrasound diagnostic accuracy rate was 89.13％ (41/46),sensitivity was 86.84％ (33/38),specificity was 100％ (8/8).Diagnostic accuracy rate of radionuclide imaging was 52.17％ (24/46),sensitivity was 52.63 ％ (20/38) and specificity was 50.00 ％ (4/8).The sensitivity of ultrasound and radionuclide imaging in diagnosis of Meckel's diverticulum had significant difference (P＜0.01).Conclusion Ultrasound in diagnosis of Meckel's diverticulum has advantages of non-invasive,no radiation,acceptable price and high sensitivity.

Objective To observe the clinical efficacy of the TESSYS (transforaminal endoscopic spine system) technique of percutaneous transforaminal endoscopic discectomy combined with oral use of Chinese medicine for the treatment of lumbar disc herniation.Methods Thirty-nine patients with lumbar disc herniation were treated by the TESSYS technique of percutaneous transforaminal endoscopic discectomy,and then received oral use of modified herbal medicine Xubi Recipe,a formula mainly having the actions of tonifying kidney and strengthening governor vessel for 4 weeks after the operation.The visual analogue scale (VAS) and Oswestry disability index (ODI) and modified MacNab criteria were employed to assessed the surgical outcomes before the operation,and 3 and 6 months after the operation.Results (1) All of the 39 cases completed the operation successfully,and were followed up for 6-12 months after the operation.(2) Three and 6 months after the operation,the VAS scores and ODI scores were obviously lower than those before the operation,and the differences were significant (P ＜ 0.05).(3) Six months after the operation,the excellent rate of clinical efficacy assessed by modified MacNab criteria was 89.74％.(4) Only 4 cases had severer transient pain and numbness in the affected limbs,and there was no occurrence of complications of permanent neural root trauma,dural tear,vascular injury,intestinal damage,spondylodiscitis or retroperitoneal hematoma.Conclusion The TESSYS technique of percutaneous transforaminal endoscopic discectomy combined with oral use of Chinese medicine is effective for the treatment of the lumbar disc herniation with the advantages of satisfactory short-term effect,less bleeding,less trauma,faster recovery and less complications.

Objective To evaluate the diagnostic value of targeted 1 024 ultra high-resolution CT scanning for the pulmonary nodules under 8 mm in diameter and its effect on follow-up protocols. Methods A total of 67 pulmonary nodules with a mean diameter of (5.97±1.34) mm in 57 patients undergoing targeted scans at Department of Radiology, Shanghai Pulmonary Hospital, Tongji University between July 2015 and August 2016 were analyzed prospectively. Two of 32 nodules with surgical resection were benign, 9 were atypical adenomatous hyperplasia (AAH), 14 were adenocarcinoma in situ (AIS), and 7 were minimally invasive adenocarcinoma (MIA). Sixteen nodules were considered to be malignant but not resected and 19 nodules were considered as benign lesions or required follow-up. The 67 pulmonary nodules were examined by conventional CT scan and targeted 1 024 ultra high-resolution CT scan. Three radiologists with 3-10 years of experience in imaging evaluated the image quality, type of nodules, diagnostic confidence using a 5-point score and gave the diagnosis result and treatment method. The film-reading results were analyzed using SPSS software. Results The images obtained by the targeted 1 024 ultra high-resolution CT scan were significantly superior to that of conventional CT in showing the margin of nodules, internal component, lobulation sign and other aspects (P<0.05). There were significant differences in judging the pure ground-glass opacity (GGO) nodules and mixed GGO nodules between the two kinds of CT images (P<0.05). The diagnostic accuracy of targeted 1 024 ultra high-resolution CT scan was significantly increased versus the conventional CT scan (P<0.05), and the same was true for the diagnostic confidence (P<0.05). The treatment methods given by the two kinds of CT images were significantly different (P<0.05), which was reflected by the decreasing number of follow-up cases and increasing numbers of surgical cases and no follow-up cases. Conclusion The targeted 1 024 ultra high-resolution CT scan can provide a better image quality for pulmonary nodules below 8 mm in diameter. For patients with pulmonary nodules which are difficult to diagnose or with insufficient confidence, further examination should be performed using a targeted 1 024 ultra high-resolution scan.

Aim To investigate the brain targeting of ginkgolide B prodrug (PGB ) and its mechanism. Methods The liquid chromatography tandem mass spectrometry (LC-MS /MS)method was applied to in-vestigate the pharmacokinetics of PGB in rat brain tis-sue after intravenous injection of PGB.Also the brain targeting was evaluated on the basis of the pharmacoki-netic parameter of PGB.The incomplete cerebral is-chemia model was induced in mouse,the effect of PGB on cerebral capillary permeability was observed by Ev-ans blue method.High performance liquid chromatog-raphy (HPLC)was used to determine the partition co-efficients (logP)of PGB in octanol-water system.PGB and P-glycoprotein (P-gp)was docked by using Mole-gro Virtual Docker (MVD)software to predict its bind-ing abilities with P-gp.The interaction of PGB with ATPase activity of human P-gp membrane was esti-mated by measuring inorganic phosphate liberation. Results The brain targeting of PGB was evaluated by treatment effective (TA ) and drug targeting index (DTI),the calculated value were 6.87 and 4.1 4 re-spectively.Preventive medication of PGB could signifi-cantly decrease cerebral capillary permeability (P <0.05).The lipo-hydropartition coefficient of PGB was higher than that of GB,their logP data were 1 .03 and 0.61 respectively.PGB displayed the stronger binding affinity with P-gp than GB according to the molecular docking calculations,their MolDock Score toward P-gp were -1 43.36 and -1 1 6.40KJ·mol -1 respectively. ATP-hydrolisis showed that PGB increased ATPase activity with a Km of approximately 237.75 μmol · L -1 ,however GB with a Km of approximately 841 .24μmol·L -1 .PGB might interact with P-gp with a high-er affinity and exhibit more effect than GB.Conclu-sion PGB is characterized by its brain targeting. Higher liposolubility of PGB results in good blood-brain permeability,which is advantageous to its brain targe-ting.Besides,PGB can effectively inhibit the efflux effect of P-gp to GB because of its increased P-gp AT-Pase activity.

A fusion protein of glucagons-like peptide-1 and human serum albumin (GLP-1/HSA) was expressed and secreted into the fermentation broth with recombinant Pichia pastoris. The productivity of expressed GLP-1/HSA could reach 63.6mg/L in 10L fermentor. After concentrated with hollow-fiber ultrafiltration membrane, GLP-1/HSA was purified from fermentation broth by hydrophobic chromatography, negative ion exchange chromatography and gel filtration chromatography in turn. The HPLC analysis showed that the purified GLP-1/HSA had an overall purity of 95.8%. Furthermore, the analysis of in vivo activity indicated that GLP-1/HSA had the bioactivity of native GLP-1, and could significantly reduce blood glucose level 4h after intraperitoneal administration. It was concluded that a great deal of GLP-1/HSA with higher purity could be harvested by Pichia pastoris expression system and the established purification methods. Preliminary studies show a new potential for developing the long-acting GLP-1 analogs for clinical applications.