In order to construct a novel multifunctional targeting nano-carrier based on pH-redox characteristics of tumor microenvironment,ketone bonds and disulfide bonds were bonded to the oligomeric hyaluronic acid (oHA) being sensitive to pH and the reduction environment.The chemical structure of oligomeric hyaluronic acid-8-mercaptomenthone 1,2-glycerolketal (oHMST) was characterized by 1H NMR,IR and ESI-MS.Curcuminloaded micelles were prepared by dialysis.The single factor investigation was carried out on the dosage form.Some properties,including particle size zeta potential,the morphology of micelles,and pH-sensitivity were studied.The materials were synthesized successfully.The micelles were spheric with a diameter of about 100 nm.The Zeta potential of the micelles was-(21.97 ± 1.08) mV.The in vitro test showed that oHMST carriers have good pH-sensitivity and redox-sensitivity.

Objective To study the mechanism of Compound berberineXiaochuangpowder on recurrent oral ulcers,and the anti-inflammatory effect.Methods The mice were divided into blank group, model group, and compound yellow hyalensis with high, medium, low dose group(2, 1, 0.5 g/kg equivalent medicine) and ibuprofen group(0.15 g/kg). Using mouse ear inflammation test by Xylene, To establish recurrent oral ulcer model by immunoassay in Rats, the mold SD rats according to random number table method is divided into blank group, model group, compound coptis sores spirit high, medium and low dose group (1, 0.5, 0.25 g/kg equivalent medicine), levamisole group (20 mg/kg), each group all gastric gavage corresponding drugs, model group, the blank group gastric gavage capacity such as pure water, a total of 30 days, observe the number of ulcers, duration and interval time, and the effection on serum IL-4, IL-8, VEGF level.Results The compound berberineXiaochuang powder high dose may significantly reduce the swelling degree of ears (7.46 ± 1.41 mg, 9.85 ± 2.71 mg vs. 16.25 ± 3.34 mg,P<0.05), reducing the number of ulcers (4.70 ± 1.27, 6.90 ± 3.70 vs. 9.90 ± 5.13,P<0.05), reduce ulcer duration (2.20 ± 1.22 d, 3.00 ± 1.05 d vs. 5.00 ± 1.15 d,P<0.05), prolonged intervals ulcers (8.00 ± 1.63 d, 5.00 ± 1.82 d vs. 2.40 ± 1.26 d,P<0.05). Compound berberineXiaochuang powder high dose can be significantly increased the level of serum IL-4 (68.92 ± 10.58 pg/ml vs. 55.18 ± 6.99 pg/ml, P<0.05) and lowered serum IL-8 (399.86 ± 62.14ng/mlvs. 578.70 ± 72.23 ng/ml,P<0.05); The compound berberine Xiaochuang powder high dose could significantly increase the expression of VEGF (41.41 ± 3.80 pg/ml、37.92 ± 3.48 pg/ml vs. 32.01 ± 4.32 pg/ml,P<0.05).Conclusions The compound berberineXiaochuang powder can increased the level of serum IL-4 and VEGF, reduced the level of IL-8, so as to achieve the treatment of recurrent oral ulcers.

Objective To compare the effects of movable artificial lumbar vertebra implantation and traditional vertebral excision and fusion on the stress of adjacent intervertebral discs,so as to provide reference for the biomechanical safety of new prosthesis implantation.Methods The total lumbar vertebra CT scan data of a healthy adult were imported into the compute r-aided software Mimics 16.0 for three dimensional reconstruction.The reconstructed three dimensional model was smoothed using computer-aided software Geomagic Studio 12.0.Subsequently,meshing,parameter setting and ligaments reconstructing were completed using computer-aided software Hypermesh 13.0 and Solidworks 2013,successfully constructing the finite element model of lumbar vertebral physiology group.On the basis of the finite element model of physiological group,three vertebral bodies and two intervertebral spaces were fused and fixed,and a simplified finite element model of fusion group was constructed.The partitioned prosthesis model was inserted into the established finite element model of physiological group,replacing the L 3 vertebral body and the adjacent two intervertebral discs in the model,constructing the finite element model of non fusion group.Three finite element models were imported into computer-aided software Abaqus/Explict and loaded under six motion modes including anteflexion,dorsiflexion,left and right rotation,and left and right bending.The stress changes of adjacent intervertebral discs were calculated.Results The maximum Mises stress of the adjacent intervertebral disc in the direction of forward flexure,dorsal extension,left and right rotation and left and right lateral bending of the three finite element models was located at the site of loading and increased with the increase of loading.Under the maximum loading,the Mises stress of adjacent intervertebral discs in the above directions in the fusion group (L1-2 respectively were 0.79,0.96,1.26,1.92,1.34,1.57 MPa while L4-5 respectively were 0.52,1.13,1.50,1.74,0.94,0.87 MPa) was significantly higher than that in the physiological group (L1-2 respectively were 0.42,0.53,0.57,0.66,0.64,0.72 MPa while L4-5 respectively were 0.23,0.29,0.68,0.63,0.37,0.34 MPa).The Mises stress of adjacent intervertebral disc in the non-fusion group (L1-2 respectively were 0.38,0.57,0.75,1.02,0.87,0.90 MPa while L4-5 respectively were 0.18,0.26,0.81,0.98,0.30,0.27 MPa) was similar to that in the physiological group,although there was some difference.Conclusion Movable artificial lumbar disc prosthesis implantation can better avoid the stress increase of adjacent intervertebral discs,and its long-term implantation in the human body is expected to reduce the incidence of degeneration of adjacent intervertebral discs.

Objective To investigate the clinical efficacy of non-fusion and fusion internal fixation with posterior pedicle screw for odontoid fractures. Methods A retrospective case control study was conducted to analyze the clinical data of 46 patients with odontoid fractures admitted to Henan Provincial People's Hospital from January 2013 to June 2015. There were 35 males and 11 females, aged 19-62 years [(36. 9 ± 1. 6)years]. The preoperative odontoid fractures were classified as type IIA in five patients, type IIB in eight, type IIC in 22, shallow type III in six according to Anderson and D'Alonzo typing. The fractures of five patients were not classified. According to the ASIA grading, the preoperative spinal cord function was graded as D or E in the 46 patients. Among the patients, 15 underwent posterior pedicle screw non-fusion internal fixation ( Group A) , with 60 pedicle screws removed 12-29 months after operation. A total of 31 patients were treated with fusion internal fixation with posterior pedicle screw ( Group B) , with 124 pedicle screws free from removal after operation. The follow-up time, operation time, intraoperative fluoroscopy time, intraoperative blood loss as well as visual analog scale (VAS), cervical rotation degree, and neck disability index ( NDI) before operation, 1 year after surgery ( when no internal fixation was removed ) and at the last follow-up were compared between the two groups. Results There were no significant differences between the two groups in the follow-up time, operation time, intraoperative fluoroscopy time, intraoperative blood loss, VAS score, neck rotation degree, NDI score before operation and at 1 year after operation (P >0. 05). There were significant differences between two groups in VAS scores, neck rotation degree, NDI scores indicating driving and walking and recreational activities at the last follow-up ( P <0. 05 ) . There were no significant differences between two groups in other NDI scores items, including neck discomfort, personal care, lifting heavy objects, reading & watching TV, headache situation, attention, working status, and sleep disorder at the last follow-up ( P> 0. 05 ) . Conclusions Posterior pedicle screw internal fixation for odontoid process fracture has good curative effect. Non-fusion internal fixation with posterior pedicle screw is more conducive to the recovery of cervical spine rotation function, the relief of neck and back pain, and the improvement of patients' driving, walking and entertainment activities.

Objective To investigate the relationship between immune tolerance and the changes of helper T cell (Th), regulatory T cell (Treg) cytokines, related signaling pathway proteins during immune tolerance process in rat models of liver transplantation. Methods The orthotopic liver transplantation rat models were established by double-cuff technique. All rats were divided into 3 groups. In the operative control group (n=6), sham operation was performed without liver transplantation. In the short-term group (n=10), the rats survived for 10 d after liver transplantation. In the immune tolerance group (n=10), the rats survived for 100 d after operation and the function of the transplanted liver was restored to normal. The expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Th1 cytokines [interferon (IFN)-γ, interleukin (IL)-2 and tumor necrosis factor (TNF)-α], Th2 cytokines (IL-4, IL-5, IL-6 and IL-13), Th17 cytokines [granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A], Treg cytokines [IL-10, transforming growth factor (TGF)-β and IL-12p] were quantitatively measured. The serum sample of rats in each group was detected by protein chip analysis. Results Compared with the operative control group, the AST level in the short-term group was significantly down-regulated, whereas the ALT level was significantly up-regulated (both P < 0.05). However, the AST and ALT levels did not significantly differ between the immune tolerance group and operative control group (both P > 0.05). In the liver tissues of rats in each group, the expression levels of Th1 cytokines IFN-γ and IL-2 in the short-term group were significantly higher than those in the operative control group (both P < 0.05). The expression level of Th2 cytokine IL-4 in the immune tolerance group was significantly lower than that in the operative control group (P < 0.05). The expression levels of Th2 cytokines IL-5, IL-6 and IL-13 in the short-term group were significantly lower than those in the operative control group (all P < 0.05). The expression level of IL-17A in the immune tolerance group was significantly higher than that in the operative control group (P < 0.05). In the immune tolerance group, the expression levels of IL-10and IL-12p were significantly higher than those in the operative control group (both P < 0.05). The expression level of TGF-β in the short-term group was significantly higher than that in the operative control group (P < 0.05). Compared with the operative control group, the expression levels of intercellular adhesion molecule (ICAM)-1, pro-platelet basic protein (Ppbp), Neuropilin-2, Notch-2 protein in the short-term group were significantly up-regulated (all P < 0.05). The expression levels of CXC chemokine ligand 17 (CXCL17), ICAM-1 and Neuroleptin-2 protein were markedly up-regulated (all P < 0.05), whereas that of B7-1 protein was significantly down-regulated (P < 0.05) in the immune tolerance group. Conclusions Treg cytokines (IL-10, TGF-β and IL-12p), IL-6, IL-17 and trans-membrane signaling pathway molecules (ICAM-1, Neuropilin-2, B7-1 proteins) play a pivotal role in the natural immune tolerance process of rat models of liver transplantation.

OBJECTIVE:To investigate the situation of hospital pharmaceutical administration in China,and provide basis for developing measures in improving the quality and safety of medication in hospitals. METHODS:According to the organization of National Health and Family Planning Commission,National Quality Control Center of Pharmaceutical Administration drafted the re-search indicators,and adopted internet survey to screen,confirm and statistically analyze the data about pharmacy staffing and drug use management of hospitals in 2014 that was completed and reported as requested by the secondary general hospitals and above in each area selected by Health and Family Planning Commission in provinces (cities,districts). RESULTS:The rates of pharmacy technicians in secondary and tertiary general hospitals were 5.2% and 4.4%,the numbers of clinical pharmacists per hundred-bed were 0.42 and 0.44 person,the numbers of dispensing prescription per person in a day were 119 and 173 in pharmacist in outpa-tient;the monitoring rates for key patients were 1.8% and 6.9%,the rates of intravenous infusion in outpatients were 12.8% and 10.1%,and inpatient were 93.1% and 90.4%;the rates of intravenous infusion of antibiotics in inpatients were 51.8% and 44.3%,and the rates of intravenous infusion of TCM were 34.7% and 29.0%,respectively. CONCLUSIONS:The problems exist-ing in pharmaceutical quality administration in China include lacking of pharmacy technicians,large workload,lacking of clinical pharmacists,imperfect pharmaceutical care model,non-standardized choice and use of intravenous infusion,etc. For these prob-lems,it is suggested to increase the propaganda of health education and management efforts of intravenous drugs,equipped with ad-equate pharmacy technicians and clinical pharmacists,continuously improve the quality evaluation system of hospital pharmaceuti-cal administration in China.

Objective:To evaluate the effect of allogenic vein replacement in treatment of borderline resectable pancreatic cancer, and to analyze risk factors of long-term stenosis.Methods:The clinical data of 77 patients with borderline resectable pancreatic cancer who underwent surgery from January 2013 to December 2021 at the Beijing Chaoyang Hospital, Capital Medical University were retrospectively analyzed. There were 34 males and 43 females, aged (61.4±10.8) years old. The peri-operative data, long-term prognosis and stenosis of allogenic vein were analysed. Risk factors of stenosis were analyzed by the Cox proportional hazards model. Patients were followed up by outpatient visits or by telephone.Results:Pancreatic cancer had invaded the junction of portal vein/superior mesenteric vein (SMV) in 41 patients, SMV in 22 patients and portal vein in 14 patients. The length of venous resection was (3.7±1.0) cm, the tumor longest diameter was (3.8±1.6) cm, lymph node metastasis was present in 57 patients, R 0 resection was carried out in 70 patients, and the postoperative complication rate was 29.9% (23/77). The survival rates in 6 months, 1-year and 2-year were 84.1%, 52.3% and 32.9% respectively. Mild venous stenosis occurred in 4 patients (5.2%), moderate stenosis in 9 patients (11.7%) and severe stenosis in 11 patients (14.3%). A vascular resection length of more than 3 cm ( RR=4.602, 95% CI: 1.657-12.781, P=0.003) and tumor recurrence ( RR=8.529, 95% CI: 1.129-64.448, P=0.038) were independent risk factors for long-term moderate and severe stenosis of allogeneic vein. Conclusion:It was safe and feasible for allogenic vein to be used to reconstruct the portal venous system in resection of borderline resectable pancreatic cancer. Long-term stenosis of the allogenic vein was related to a length of vascular resection of more than 3 cm and recurrence of tumor.

Objective To investigate the guiding role of quantitative evaluation system of immune status in the individualized management of immunosuppressants for the recipients after liver transplantation. Methods Clinical data of 239 liver transplant recipients were retrospectively analyzed. MingDao Immune Cell Analysis (MICA) was established. All recipients were divided into two groups according to the adjustment regimens of immunosuppressants. The immunosuppressant regimen was adjusted according to MingDao Immune System Score (MISS) in the MISS group (n=84), and the medication plan was empirically adjusted during the same period in the control group (n=155). According to the time of postoperative detection (t), the recipients in the MISS group were divided into subgroup A (t ≤ 28 d, n=78), subgroup B (28 d < t ≤ 6 months, n=68), subgroup C (6 months < t ≤ 12 months, n=18), subgroup D (12 months < t ≤ 24 months, n=18) and subgroup E (t > 24 months, n=19). In the MISS group, postoperative MISS scores of recipients in subgroups A-E were analyzed. The incidence of acute rejection and opportunistic infection and the overall survival rate were statistically compared between the MISS and control groups. Results The MISS scores in subgroups A-E were -7.0 (-13.2, -2.0), -2.0 (-5.8, 1.8), -0.5 (-7.3, 2.8), -2.0 (-4.5, 3.3) and -3.0 (-6.0, 1.0), respectively. The immune status of the recipients was gradually improved over postoperative time, and the difference between two groups was statistically significant (P < 0.05). In the MISS group, 15% (13/84) of the recipients developed acute rejection, and 27% (42/155) in the control group, and the difference was statistically significant (P < 0.05). In the MISS group, the MISS score of the recipients with acute rejection was 0 (-2.5, 3.5), and -5.0 (-12.0, -1.0) for their counterparts without acute rejection, and the difference was statistically significant (P < 0.05). In the MISS group, 2% (2/84) of the recipients presented with postoperative opportunistic infection, and 9% (14/155) in the control group, and the difference was statistically significant (P < 0.05). In the MISS group, the 1- and 3-year overall survival rates were 86.9% and 79.8%, and 83.2% and 76.8% in the control group, and no significant difference was observed between two groups (P > 0.05). Conclusions MICA and MISS score may reflect the immune status of liver transplant recipients, and guide the individualized management of administration of immunosuppressants after liver transplantation.

Objective:To investigate the effect of lymph node metastasis on the prognosis of patients with G2 phase stage pancreatic neuroendocrine neoplasm(pNEN).Methods:A retrospective case control study was conducted to analyze the case data of 368 patients with pancreatic neuroendocrine tumors in G2 phase stage from January 1, 2010 to December 31, 2016 in SEER database, including 174 males and 194 females. According to whether lymph nodes were metastatic, they are divided into lymph node non metastatic (N0) group ( n=272) and lymph node metastatic (N1) group ( n=96). The Kaplan-Meier method and Log-rank test were used to compare the overall survival rate (OS) of patients in the N0 and N1 groups. The COX proportional risk model was used to evaluate whether N stage was an independent risk factor affecting prognosis. Count data were expressed as cases and percentage(%), and Chi-square test was used for comparison between the groups. Results:Among all patients, the OS of patients in the N0 group was better than that of patients in the N1 group. The OS of N0 patients at 1, 3, and 5 years was 96.3%, 92.7%, and 85.6%, respectively, while the OS of N1 patients at 1, 3, and 5 years was 92.6%, 82.1%, and 82.1%, respectively ( P=0.014). Multivariate analysis showed that age ( HR=2.245, 95% CI: 1.126-4.475, P=0.022) and N stage ( HR=0.457, 95% CI: 0.237-0.883, P=0.020) were independent prognostic factors for G2 phase pNEN patients. Conclusion:Lymph node metastasis is one of the independent prognostic factors in patients with G2 phase stage pNEN.

Objective To develop a new type of lumbar prosthesis,movable artificial lumbar vertebral body (MALV) and evaluate the stability and activity of the prosthesis by in vitro biomechanical test.Methods Fifteen adult fresh lumbar spine specimens were randomly divided into three groups:intact group,fusion group and non-fusion group.The anatomical parameters of L2 vertebral body and adjacent intervertebral discs were collected by software (Mimics 16.0,Materialise Company,USA) and the new prosthesis was personalized by 3D printing and mechanical processing.All specimens in fusion group and in non-fusion group were implanted with titanium cage,titanium plate and MALV respectively after partial resection of L2 vertebra and adjacent intervertebral disc.No other intervention was conducted on physiological specimens.All specimens were examined by imaging to determine the position of the prosthesis and the condition of the spinal cord.Specimens in all groups were subjected to a 7.5 N · m load biomechanical test in flexion,extension,left and right lateral bending,left and right rotation aiming to evaluate the mobility of operative site and adjacent discs.Results The new prosthesis consists of three parts,vertebral body,intervertebral disc and composite material ball.All 15 cadavers were free of spinal deformity,fracture and osteoporosis.Postoperative radiographic examination indicated no prosthesis displacement and spinal compression without adverse phenomena.The results in vitro mechanical test were as followed.There was no statistical difference in ROM of the T12L1 intervertebral in non-fusion group (3.68°±0.86°,3.52°± 0.86°,2.64°±0.93°,2.58°±0.76° respectively) and in intact group (3.98°±0.90°,3.74°±0.91°,2.94°±1.10°,2.96°±0.86° respectively) in flexion,extension,left and right lateral bending (P＞0.05).The ROM of the T12L1 intervertebral in fusion group (5.28°±0.83°,5.32°±0.42°,4.72°±1.10°,4.94°±1.17° respectively) was significantly larger than that in intact group and non-fusion group (P＜0.05).There was no statistically significant difference between the ROM of L1.2 and L2.3 intervertebral in flexion,extension and left and rightlateral bending in the non-fusion group (ROM of L1.2 were 4.62°±0.51 °,4.34°±0.67°,3.16°±0.55°,3.28°±0.41 ° respectively;ROM of L2.3 were 4.54°±0.58°,4.36°±0.65°,3.26°±0.21°,3.42°±0.37° respectively) and the intact group (ROM of L1.2 were 4.10°±0.53°,3.72°±0.42°,2.74°±0.50°,3.04°±0.40° respectively;ROM of L2.3 were 4.26°±0.72°,4.08°±0.77°,3.00°±0.36°,3.20°±0.31° respectively) (P＞0.05).The ROM of L1.2 and L2.3 in intact group and in non-fusion group were significantly greater than those in the fusion group (ROM of L1.2 were 1.10°± 0.35°,1.28°±0.31°,0.84°±0.34°,0.80°± 0.43° respectively;ROM of L2.3 were 1.14°±0.30°,1.18°±0.28°,0.94°± 0.36°,1.06°±0.32°) (P＜0.05).There was no statistically significant difference in the ROM of the T12-L3 full segment in the left and right rotation of the three groups (Intact group:4.47°± 0.99°,4.40°±0.70°;Non-fusion group:4.60°±0.90°,4.50°±0.77°;Fusion group:3.85°±0.50°,3.72°±0.70°)(P＞0.05).Conclusion The MALV can retain the mobility of the operative site in flexion,extension,lateral bending and rotation.Furthermore,it can effectively avoid the increased mobility of adjacent segment intervertebral.After implantation,the prosthesis can obtain satisfied immediate stability.