Molecular dynamics simulation technology relies on Newtonian mechanics to simulate the motion of molecular system of the real system by computer simulation. It has been used in the research of self-assembly processes illustration and macroscopic performance prediction of self-assembly nano-drug delivery systems (NDDS) in recent years, which contributes to the facilitation and accurate design of preparations. In this review, the definitions, catalogues, and the modules of molecular dynamics simulation techniques are introduced, and the current status of their applications are summarized in the acquisition and analysis of microscale information, such as particle size, morphology, the formation of microdomains, and molecule distribution of the self-assembly NDDS and the prediction of their macroscale performances, including stability, drug loading capacity, drug release kinetics and transmembrane properties. Moreover, the existing applications of the molecular dynamic simulation technology in the formulation prediction of self-assembled NDDS were also summarized. It is expected that the new strategies will promote the prediction of NDDS formulation and lay a theoretical foundation for an appropriate approach in NDDS studies and a reference for the wider application of molecular dynamics simulation technology in pharmaceutics.

This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.
Rats ; Animals ; Micelles ; Tissue Distribution ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Rats, Inbred SHR ; Isoflavones/pharmacology*

Inflammation alters the neural stem cell (NSC) lineage from neuronal to astrogliogenesis. However, the underlying mechanism is elusive. Autophagy contributes to the decline in adult hippocampal neurogenesis under E. coli lipopolysaccharide (LPS) stimulation. SRY-box transcription Factor 2 (SOX2) is critical for NSC self-renewal and proliferation. In this study, we investigated the role of SOX2 in induced autophagy and hippocampal adult neurogenesis under LPS stimulation. LPS (5 ng•100 g -1 •hour -1 for 7 days) was intraperitoneally infused into male Sprague–Dawley rats (8 weeks old) to induce mild systemic inflammation. Beclin 1 and autophagy protein 12 (Atg12) were significantly upregulated concurrent with decreased numbers of Ki67- and doublecortin (DCX)-positive cells in the dentate gyrus. Synchronically, the levels of phospho(p)-mTOR, the p-mTOR/mTOR ratio, p-P85s6k, and the p-P85s6k/P85s6k ratio were suppressed. In contrast, SOX2 expression was increased. The fluorescence micrographs indicated that the colocalization of Beclin 1 and SOX2 was increased in the subgranular zone (SGZ) of the dentate gyrus. Moreover, increased S100β-positive astrocytes were colocalized with SOX2 in the SGZ. Intracerebroventricular infusion of 3-methyladenine (an autophagy inhibitor) effectively prevented the increases in Beclin 1, Atg12, and SOX2. The SOX2 + -Beclin 1 + and SOX2 + -S100β + cells were reduced. The levels of p-mTOR and p-P85s6k were enhanced. Most importantly, the number of DCX-positive cells was preserved. Altogether, these data suggest that LPS induced autophagy to inactivate the mTOR/P85s6k pathway, resulting in a decline in neural differentiation. SOX2 was upregulated to facilitate the NSC lineage, while the autophagy milieu could switch the SOX2-induced NSC lineage from neurogenesis to astrogliogenesis.

OBJECTIVETo investigate the hypoglycemic characteristics of hospitalized elderly patients with type 2 diabetes mellitus (T2DM).

METHODSFrom January, 2014 to December, 2015, the data of 58 565 blood measurements using a standard blood glucose monitoring system (BGMS) were collected from 1187 cases of patients with type 2 diabetes during hospitalization in the Department of Endocrinology, Guangdong General Hospital (Guangzhou, China). Stratified analyses were conducted by dividing the patients into 3 age groups, namely <45 years group (128 cases), 45-64 years group (594 cases), and ≥65 years group (465 cases). The incidence and time distribution of hypoglycemia in these patients were compared among the 3 age groups.

RESULTSThe risk of hypoglycemia increased with age. Compared with those below 45 years of age, the patients beyond or equal to 65 years had a significantly increased hypoglycemic density (0.95% vs 0.40%, P<0.001), a higher proportion of patients with hypoglycemia (28.17% vs 10.94%, P<0.001), and greater patient-days with hypoglycemia (4.48% vs 1.76%, P<0.001). In the elderly patients, hypoglycemia occurred most frequently before dawn, at which time the hypoglycemic density was 2.66% in patients ≥65 years of age, significantly higher than that in patients below 45 years (1.09%, P<0.05) and between 45 and 64 years (1.90%, P<0.05); the proportion of patients with hypoglycemia was also significantly higher in the elderly patients (14.57%) than in those below 45 years (3.77%, P<0.02) and between 45 and 64 years (9.42%, P<0.02). The proportion of patients with recurrent hypoglycemia (≥2 times) was significantly higher in patients ≥65 years (13.33%) than in younger patients (2.34% in <45 years group and 9.43% in 45-64 years group, P<0.05).

CONCLUSIONThe hypoglycemic risk in hospitalized elderly patients with T2DM is significantly higher than that in younger patients, especially before dawn and in terms of recurrent hypoglycemia. Clinicians should develop differential blood glucose monitoring and management strategies for these elderly patients to improve the clinical safety.

OBJECTIVETo investigate the clinical effect of bridging fixation with locking plate for the Seinsheimer type V subtrochanteric femoral fracture.

METHODSFrom March 2009 to September 2014,18 cases of Seinsheimer type V subtrochanteric femoral fracture were treated by open reduction and bridging fixation with locking plate through proximal and distal approach including 16 males and 2 females with an average age of 41 years old ranging from 22 to 67 years old. Among them, 12 cases caused by traffic accident, 5 cases by falling, 1 case by heavy aboving. All cases were fresh and closed fractures. Time between injury and operation was from 4 to 9 days with an average of 6.2 days. Of them, 11 cases were fixed with reverse LISS and the other 7 cases were fixed with anatomical locking plates of proximal femur.

RESULTSThe mean time of operation was 110 min (ranged from 90 to 155 min). The mean blood loss during operation was 425 ml (ranged from 350 to 650 ml) and 16 cases got blood transfusion which was meanly 300 ml. The mean hospital time was 14 days (ranged from 12 to 18 days). The mean duration of followed up was 11.8 months (ranged from 8 to 22 months). The mean time of bone union was 6.6 months (ranged from 5 to 8 months). There was not any complication such as infection, implant failure, hip varus, external rotation deformity of low limb or fat embolism. The Sanders hip scores were 53.22 ± 6.48, the result was excellent in 12 cases and good in 6 cases at the last follow-up.

CONCLUSIONUnder the principle of biological osteosynthesis, treatment of Seinsheimer type V subtrochanteric femoral fracture with bridging locking plate fixation has such advantages as high mechanism, less interference of blood supply, stable fixation and little complication. It is a safe and idea way for the treatment of the Seinsheimer type V subtrochanteric femoral fracture.

Adult ; Aged ; Bone Plates ; Female ; Fracture Fixation, Internal ; methods ; Hip Fractures ; surgery ; Humans ; Male ; Middle Aged

OBJECTIVETo compare the effects of close reduction combined with minimally invasive percutaneous plate osteosynthesis for distal fracture of tibial shaft.

METHODSFrom March 2009 to May 2013, there were 124 patients (89 males and 35 females, 30 of them were injured in a traffic accident and 94 were falling down in daily life, the ages ranging from 21 to 81 years old) who suffered from distal fracture of tibial shaft. Sixty-six patients (48 males and 18 females, 45 cases of type A, 12 cases of type B and 9 cases of type C) were treated with close manipulative reduction combined with minimally invasive percutaneous plate fixation. After close reduction, a minimal incision was made and a anatomic plate was inserted just along the medial tibia periostea, and then the fracture was fixed without fracture exposure. The other 58 patients (41 males and 17 females, 41 cases of type A, 10 cases of type B and 7 cases of type C) were treated with conventional open reduction and internal fixation. Length of the incision, operating time, early postoperative pain (recorded using the Visual Analog Scale score) and the outcome results (recorded using the evaluation standard of Johner-Wruhs) were compared.

RESULTSThe length of incision was meanly (7.34 ± 1.42) cm in MIPPO group and (21.82 ± 2.35) cm in ORIF group; operation time was (44.48 ± 10.00) min in MIPPO group and (59.42 ± 11.84) min in ORIF group. The postoperative radiographs verified good position of all screws and satisfactory bone fracture reduction in both groups. All the patients were followed up, and the duration ranged from 10 to 24 months (mean 15.2 months) in both groups. In MIPPO group,only one patient had delayed union and got union after Chinese herb therapy. The other 65 patients got bony union during 15 to 20 weeks. While in ORIF group, 3 patients suffered from nonunion and received reoperation with bone grafting, and 4 patients got bone infection.

CONCLUSIONTreatment of distal fracture of tibial shaft, combined with close reduction and MIPPO technique, has the advantages such as less invasion, less damage of blood supply, simplified procedure of operation and higher union rate, which is an ideal methods and is accordant to the biological demand.

Adult ; Aged ; Aged, 80 and over ; Bone Plates ; Case-Control Studies ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Manipulation, Orthopedic ; methods ; Middle Aged ; Tibial Fractures ; therapy

OBJECTIVETo observe the clinical efficacy of penyan pill (PP) in treating ureaplasma urealyticum (UU) infection patients of qi deficiency blood stasis syndrome (QDBSS).

METHODSTotally 188 UU infection patients of QDBSS were randomly assigned to two groups, the treatment group and the control group. Patients in the treatment group were treated with PP (10 g each time, thrice daily, 14 consecutive days as one therapeutic course), while those in the control group took azithromycin (10 g each day, 7 consecutive days as one therapeutic course). They were continually treated for 3 therapeutic courses. The clinical symptom integrals were observed in the two groups before and after treatment. The short-term efficacy was judged. Their recurrence rates were followed-up to assess their long-term efficacies.

RESULTSThe total effective rate of the comprehensive efficacy in the treatment group was 91.4%, while it was 79. 3%in the control group, showing no statistical difference between the two groups (P > 0.05). Better effects were obtained in improving Chinese medical clinical symptoms in the treatment group (P <0.01). There was no statistical difference in the negative conversion rate between the two groups after treatment (P >0. 05). There was statistical difference in the recurrence rate between the two groups (12. 82% vs 54.76%,P <0. 05).

CONCLUSIONSPP showed equivalent effects in treating UU infection patients of QDBSS to those of azithromycin. But PP showed obvious advantages over azithromycin in improving Chinese medical syndromes.

Adult ; Azithromycin ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Ureaplasma Infections ; diagnosis ; drug therapy ; Ureaplasma urealyticum

Objective To explore the effect of continue nursing out of hospital on the rehabilitation patients with first onset schizophrenia and to provide theoretical guidance for the development of hospital extended care.Methods Totals of 120 patients with first onset schizophrenia were randomly divided into study group and control group,each group 60 cases. Study group received continue nursing interventions out of hospital in two stages,control group only received conventional treatment,nursing,discharge instruction,and followed up one year.Medication compliance,disease recurrence and reemployment of patients were recorded.After patients discharged six months and one year,they were investigated with Brief psychotic symptoms scale (BPRS) and comprehensive assessment of quality of life questionnaire (GQOLI-74).Results In study group,there was 39 patients complied doctors' advice,7 patients' disease recurred and 13 patients were reemployment,while 26 patients complied doctors' advice,17 patients' disease recurred and 4 patients were reemployment in control group,and the differences were statistically significant (x2 =5.673,5.208,5.551,respectively;P＜0.05).There was no significant difference on the BPRS scores in two groups before implemented continue nursing outside hospital ( P ＞ 0.05 ) ; while after implemented continue nursing,the total score of BPRS in study group was (54.34 ± 6.608 ) higher than ( 43.63 ± 5.47 ) in control group,and the differences were statistically significant(t =6.749,P ＜ 0.01 ).One year later,the EQOL-74 score in physical function (62.14 ± 7.16),psychological function ( 61.54 ± 7.14) and social function ( 60.42 ± 5.28 ) in study group were higher than that of control group that was (62.14 ± 7.16),( 61.54 ± 7.14 ),( 60.42 ± 5.28 )respectively,and the differences were statistically significant ( t =3.304,3.259,3.959,respectively; P ＜ 0.01 ).Comparison of medication compliance,and ratio between two groups,the differences were statistically significant (P ＜ 0.05).Condusions Continue nursing care can improve the social function of patients with first onset schizophrenia,improve their quality of life,promote their recovery and return to society.

BACKGROUNDOff-label application of drug-eluting stents (DES) during percutaneous coronary intervention (PCI) was not uncommon in daily practice, however DES in treating Chinese patients with complex lesion subset was under-investigated. The primary objective of the FIREMAN registry was to evaluate the long term efficacy and safety of the Firebird sirolimus-eluting stent (SES) in treating patients with complex coronary lesions. Here we report the mid-term of one-year clinical outcomes and eight-month angiographic follow-up results of FIREMAN registry.

METHODSThe FIREMAN registry was a prospective multi-center registry, which included 1029 consecutive patients undergoing PCI with Firebird SES implantation between September 2006 and July 2007 in 45 centers in China. The clinical follow-up was designed to be performed at 1, 6, 12, 18, 24, 30 and 36 months post index procedure, and non-mandatory angiographic follow-up at 8 months was planned. One hundred percent site monitoring was conducted.

RESULTSLong lesions (59.2%), multi-vessel disease (50.4%), and small vessel disease (31.6%) were mostly found in angiography. Major adverse cardiac events (MACE) occurred in 51 (5.1%) patients at 1 year clinical follow-up, including cardiac mortality in 6 (0.6%), non-fatal myocardial infarction in 11 (1.1%), and target lesion revascularization in 36 (3.5%) of the patients. Definite and probable stent thrombosis (ST) by Academic Research Consortium (ARC) definition occurred in 12 (1.36%) patients at one-year clinical follow-up. The 8-month binary restenosis rate was 5.7% in-segment and 4.3% in-stent, respectively. Late lumen loss was (0.21 ± 0.40) mm in-segment and (0.23 ± 0.36) mm in-stent, respectively. Furthermore, Cox regression analysis revealed that diabetes, small vessel diameter, and chronic total occlusion were independent predictors of ST.

CONCLUSIONSThe results showed that the Firebird SES was effective and safe in treating Chinese patients with complex coronary lesions and occurrence of ST rate at one-year clinical follow-up was acceptable, however further long-term follow-up was still necessary. (NCT00552656)

Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; methods ; Asian Continental Ancestry Group ; Coronary Angiography ; Coronary Disease ; diagnostic imaging ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Sirolimus ; therapeutic use ; Treatment Outcome

Adenocarcinoma ; pathology ; Carcinoma ; pathology ; Carcinoma, Squamous Cell ; pathology ; Humans ; Nasopharyngeal Neoplasms ; classification ; pathology ; World Health Organization