Objective To evaluate the role of M3 muscarinic acetylcholine receptor (M3 mAChR) in the release of glycinergic neurotransmitter by using oxotremorine-M (Oxo-M: a nonselective mAChR agonist) and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP: a highly selective M3mAChR antagonist). Methods Twenty male 3-4 weeks old SD rats weighing 160-180 g after successful intrathecal catheterization were randomized into 2 groups (n = 10 each): normal saline group (group NS) and pertussis toxin (group PTX).Pertussis toxin 1.5 μg/10 μl was injected IT in group PTX, while in group NS normal saline 10 μl was injected IT instead. The animals were killed at day 7 after injection. The spinal cords were removed and sliced and placed in artificial CSF. Glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs) were measured in spinal lamina Ⅱneurons using whole-cell voltage-clamp technique. Five minutes after sealing, Oxo-M (final concentration 3 μ mol/L) was added. Oxo-M was then completely washed out 3 min later and 4-DAMP (final concentration 25 nmol/L) was added after 5 min of stabilization. In the presence of 4-DAMP, Oxo-M (final concentration 3 μmol/L) was added again 3 min later. sIPSCs were recorded before addition of Oxo-M (T1), 3 min after addition of Oxo-M (T2), 3 min after addition of 4-DAMP (T3), 3 min after the second addition of Oxo-M (T4). Results Compared with the baseline value at T1 , Oxo-M significantly increased the frequency of glycinergic sIPSCs at T2without changing the amplitude at T2-4 in both groups. The frequency of sIPSCs was significantly lower at T4 than at T2 in both groups (P ＜ 0.05 or 0.01). There was no significant difference in both frequency and amplitude of glycinergic sIPSCs between the two groups. Conclusion M3 mAChR plays a predominant role in the release of glycinergic transmitter in the spinal lamina Ⅱ neurons in rats.

Various geometric shapes and structures self-assembled of amphiphilic lipids when present in an aqueous environment, as active delivery vehicles, are becoming one of focuses of drug delivery system. Lipid-based cubic liquid crystalline nanoparticles (or Cubosomes) consisting of "honeycombed (cavernous)" structure spontaneously formed when a certain concentration of amphiphilic lipids dispersed in aqueous solution has curved bicontinuous lipid bilayer in three dimensions, separating two congruent networks of water channels. Its unique structure consists of internal double water channels and large interfacial areas, which reveal great flexibility in encapsulation efficiency of various polarities and amount of drugs, and has variegated range of drugs encapsulated. As a drug delivery vehicle, high drug payloads, stabilization of peptides or proteins and simple preparation process are also its advantages. The ability of cubic phase to incorporate and control release of drugs of varying size and polar characteristics, and biodegradability of lipids make it an interesting drug delivery system for various routes of administration, including oral, topical (or mucosal) and intravenous administrations, with extensive application in a multitude of dosage forms. Furthermore, a number of different proteins in cubic phase appear to retain their native conformation and bioactivity, and are protected against chemical and physical inactivation. In this paper, investigations of lipid-based cubic liquid crystalline nanoparticles are reviewed and summarized, with a hope to provide a reference for its in-depth study. At the end, the authors made a development prospect of this novel excellent candidate for active ingredients delivery vehicle.
Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Lipids ; administration & dosage ; chemistry ; Liquid Crystals ; chemistry ; Nanoparticles

BACKGROUND:Jumonji domain-containing histone demethylase (JMJD) can promote osteoblast differentiation, and estrogen-related receptor alpha (ERRα) can promote osteoblast differentiation and increase bone formation. However, little is reported on the association between postmenopausal osteoporosis andJMJD and ERRα. OBJECTIVE: To study the changes in the JMJD2 family expression in patients with postmenopausal osteoporosis. METHODS: Postmenopausal patients with osteoarthritis of the hip scheduled for total hip arthroplasty, aged 50-70 years, were enroled, including 10 postmenopausal osteoporosis patients (experimental group) and 10 patients with no postmenopausal osteoporosis (control group). During the arthroplasty, the cancelous bone specimens from the femoral head were colected. Then, immunohistochemistry and western blot assay were used to detect expression of histone demethylase (JMJD2A, JMJD2B), histone methylation (H3K9me3, H3K36me3) and ERRα. RESULTS AND CONCLUSION:In the experimental group, the expressions of JMJD2A, JMJD2B and ERRαwere from weakly positive to positive; these expressions were significantly lower in the experimental group than the control group (P < 0.05). The expressions of H3K9me3 and H3K36me3 were significantly higher in the experimental group than the control group (P < 0.05). These findings indicate that the expression of JMJD2A and JMJD2B is consistent with the expression of ERRα in the patients with postmenopausal osteoporosis, and JMJD is likely to serve as an antagonistic enzyme of osteoporosis.

OBJECTIVETo assess the clinical therapeutic effect of acupuncture with meridian acupoints combined with three Anmian acupoints.

METHODSSixty subjects were randomly divided into two groups: the acupuncture with meridian acupoints group (Group A), and the acupuncture with meridian acupoints and three Anmian acupoints group (Group B) with 30 cases in each group. After 4-week treatment, the clinical therapeutic effects and scores for the Pittsburgh Sleep Quality Index (PSQI), depression index and anxiety index were assessed in the two groups before and after treatment.

RESULTSThe total effective rate of therapy was higher in Group B (93.3%) compared with that in the Group A (66.7%, P<0.05). When comparing after treatment with before treatment, there were significant differences in the PSQI score of sleep quality, time to sleep, sleep time, sleep disorders in Group A (P <0.05) and significant differences in the PSQI score of sleep quality, time to sleep, sleep time, sleep disorders and daytime disorders in Group B (P <0.01 or P<0.05). There were significant differences in total PSQI score between Group A and Group B (P<0.05). Both groups improved the depression and anxiety state of the patients, but acupuncture with meridian acupoints combined with three Anmian acupoints was more effective than meridian acupoints alone (P<0.05).

CONCLUSIONAcupuncture with meridian acupoints combined with three Anmian acupoints can improve the sleeping quality of patients with insomnia.

Acupuncture Points ; Adult ; Aged ; Anxiety ; complications ; therapy ; Depression ; complications ; therapy ; Female ; Humans ; Male ; Middle Aged ; Sleep Initiation and Maintenance Disorders ; complications ; therapy ; Treatment Outcome ; Young Adult

Objective To study correlation between biochemical markers of bone metabolism and postmenopausal osteoporot-ic vertebral fractures.Methods The clinical data of 100 cases with postmenopausal osteoporotic were study retrospectively.Fifty patients were postmenopausal osteoporotic,the rests were postmenopausal osteoporotic vertebral fractures.Lumbar spine,hip BMD,serum P1NP,β-CTX,N-MID,25-(OH)VitD and Ca2 + were recorded.Results There was a significant difference among ser-um P1NP,β-CTX and 25-(OH)VitD(P <0.05 ).There was positive correlation between postmenopausal osteoporotic vertebral fracture with serum P1NP (P <0.05),and negative correlation with serum 25-(OH)VitD (P <0.05),but had no correlation with serumβ-CTX (P >0.05).Conclusion Serum P1NP and 25-(OH)VitD could predict risk of postmenopausal osteoporotic vertebral fractures.Biochemical markers of bone metabolism combined with BMD could reduce postmenopausal osteoporosis fractures.

BACKGROUNDWith the widespread use of ventilators in treating critically ill patients, the morbidity of ventilator-induced lung injury (VILI) is increasing accordingly. VILI is characterized by a considerable increase in microvascular leakiness and activation of inflammatory processes. In this study we investigated the effects of inflammatory mediators in VILI rat serum on endothelial cytoskeleton and monolayer cellular permeability, as well as the therapeutic effect of ulinastatin, to explore the pathogenesis and the relationship between biotrauma and lung oedema induced by VILI.

METHODSThirty healthy male Sprague-Dawley rats were randomly divided into three groups: group A (normal tidal volume ventilation), group B (high tidal volume ventilation) and group C (high tidal volume ventilation plus ulinastatin). The serum of each rat after ventilation was added to endothelial cell line ECV-304 medium for two hours to observe the effects of serum and/or ulinastatin on endothelial fibrous actin and permeability.

RESULTSCompared to rats ventilated with normal tidal volume, serum of rats ventilated with high tidal volume caused a striking reorganization of actin cytoskeleton with a weakening of fluorescent intensity at the peripheral filament bands and formation of the long and thick stress fibres in the centre resulting in endothelial contraction and higher permeability. Prior treatment with ulinastatin lessened the above changes significantly. The changes of permeability coefficient of endothelial permeability after group A, B or C rats serum stimulation were (6.95 +/- 1.66)%, (27.50 +/- 7.77)% and (17.71 +/- 4.66)% respectively with statistically significant differences (P < 0.05) among the three groups.

CONCLUSIONSThe proinflammatory mediators in the serum of the rats given high tidal volume ventilation increases endothelial permeability by reorganizing actin cytoskeleton, and pretreatment with ulinastatin lessens the permeability by inhibiting of proinflammatory mediators.

Actins ; analysis ; metabolism ; Animals ; Anti-Inflammatory Agents ; therapeutic use ; Cell Membrane Permeability ; drug effects ; Cells, Cultured ; Endothelial Cells ; drug effects ; metabolism ; physiology ; Glycoproteins ; therapeutic use ; Humans ; Lung ; drug effects ; metabolism ; Lung Diseases ; etiology ; physiopathology ; prevention & control ; Lung Injury ; Male ; Microscopy, Fluorescence ; methods ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Respiration, Artificial ; adverse effects ; Tidal Volume ; drug effects ; Ventilators, Mechanical ; adverse effects

The present study aimed to investigate the mRNA expression levels of collagen, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) in the left and right atria in patients with chronic atrial fibrillation (CAF). Forty five patients with valvular heart disease were sampled in this study, including 18 patients with sinus rhythm (SR), 27 patients with CAF. Clinical data of these patients were collected, and the left and right atrial appendages were obtained from these patients during heart valvular replacement surgery. The mRNA levels of collagen type I, collagen type III, MMP1, MMP9, TMP1 of the atria were then measured by semi-quantitative RT-PCR. The results obtained were as follows. Compared to those in SR group, in atria of CAF group, the mRNA levels of collagen type I, MMP1 and MMP9 increased (P<0.05), while the mRNA level of TMP1 decreased (P<0.01). There were no significant differences in the mRNA levels of collagen type I, collagen type III, MMP1, MMP9 and TMP1 between the left and right atria of SR group (P>0.05). In CAF group, the mRNA level of MMP1 in the right atrium was higher than that in the left atrium (P<0.05), however, the mRNA level of MMP9 in the left atrium was higher than that in the right atrium (P<0.01). In both the left and right atria, the mRNA of collagen type I was positively correlated with the corresponding atrial diameter; the mRNA of MMP1 and MMP9 was positively correlated with the mRNA of collagen type I, and was negatively correlated with the mRNA of TMP1. These results suggest that the increased level of collagen type I associated with selective upregulation of MMP1, 9 and downregulation of TMP1, 9 in the atrium might be the molecular basis of atrial interstitial fibrosis in patients with CAF. Moreover, during CAF development, there is difference in the expression of MMPs between the left and right atria.
Aged ; Atrial Fibrillation ; physiopathology ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Heart Atria ; metabolism ; Humans ; Matrix Metalloproteinase 1 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; RNA, Messenger ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism

Objective To evaluate the clinical efficacy and prognostic factors of limited-stage small cell lung cancer ( LS-SCLC) treated with 125 I radioactive seed implantation guided by CT combined with systemic chemotherapy. Methods A total of 128 limited-stage small cell lung cancer patients were treated with 125 I radioactive seed implantation combined with chemotherapy from Jun 2008 to Jun 2012 in Tianjin Medical University Second Hospital. Theχ2 test was used to analyze the influencing factors of short-term efficacy. Survival rate was calculated by Kaplan-Meier method, single factor analysis was performed by Log-rank, and multivariate analysis was performed by Cox proportional hazard model. Results Totally 128 patients finished the treatment. The overall response rate was 86.7％ ( 111/128 ) after 6 months of treatment. The 1-, 2-and 3-year overall survival rate was 77.9％, 39.8％and 28.0％, respectively, and the median survival time was 21.0 months. The univariate analysis showed that the following factors were main prognostic factors:age, performance status ( PS) , hemoglobin≥120 g/L before treatment, smoking index, the maximum diameter of tumor, neuron-specific enolase before treatment, subscribe for prophylactic cranial irradiation ( PCI) , number of chemotherapy cycle, chemotherapy response, prescribed dose ( PD ) , postoperation dose covering 100％ volume ( D100 ) , remedial model. multivariate analysis revealed that age, PS, hemoglobin≥120 g/L before treatment and PD, the maximum diameter of tumor, number of chemotherapy cycle, chemotherapy response, and remedial model were the independent prognostic factors for survival. 29 patients of 128 suffered from aerothorax and the incidence rate of aerothorax was 27.7％. Totally 16 patients occurred hemoptysis and theincidence rate was 12.5％. Conclusions 125 I radioactive seed implantation therapy showed good effecacy in the treatment of LS-SCLC. Age, PS, hemoglobin≥120 g/L before treatment, the maximum diameter of tumor, number of chemotherapy cycle, chemotherapy response, and remedial model might be the main prognostic factors for LS-SCLC patients.

OBJECTIVETo investigate the effects of inflammatory mediators in the serum of rats with ventilator-induced lung injury (VILI) on endothelial cellular cytoskeleton and monolayer cellular permeability and explore the molecular mechanism of VILI-induced lung edema.

METHODSThirty healthy male SD rats were divided into 3 groups, namely group A with normal tidal volume ventilation, group B with high tidal volume ventilation and group C with high tidal volume ventilation plus ulinastatin treatment. The serum was collected from each rat after ventilation and added into endothelial cell line ECV-304 culture medium, and 2 h later the changes of F-actin and cell permeability were observed.

RESULTSCompared to sera from rats with normal tidal volume ventilation, the sera of rats with high tidal volume ventilation caused obvious reorganization of actin cytoskeleton with weakened fluorescent intensity at the peripheral filament bands and formation of long and thick stress fibers in the center, which resulted in endothelial contraction and increased cell permeability. Pretreatment with ulinastatin could lessen these changes significantly. The percentage in change of permeability coefficient (Ppa%) after stimulation with the sera of rats in groups A, B and C was (6.95+/-1.66)%, (27.50+/-7.77)%, and (17.71+/-4.66)%, respectively, showing statistically significant differences (P<0.05).

CONCLUSIONThe pro-inflammatory mediators in the serum of rats with high tidal volume ventilation increases endothelial cell permeability by reorganizing actin cytoskeleton, and pretreatment with ulinastatin can lessen the hyperpermeability by inhibiting multiple pro-inflammatory mediators.

Actins ; metabolism ; Animals ; Cell Line ; Endothelial Cells ; drug effects ; metabolism ; Glycoproteins ; pharmacology ; Humans ; Inflammation Mediators ; antagonists & inhibitors ; metabolism ; Male ; Permeability ; drug effects ; Rats ; Rats, Sprague-Dawley ; Ventilator-Induced Lung Injury ; blood ; metabolism ; pathology

OBJECTIVETo evaluate the long-term therapeutic effect and histologic result of ADM combined with autologous thin split-thickness skin graft.

METHODS23 patients were treated with acellular dermal matrix (ADM) combined with autologous thin split-thickness skin graft. The patients were followed up at 3, 6, 12, and 18 months after operation. The histological analysis was also performed.

RESULTS3, 6, 12, 18 months after operation, the composite skin grafts became smooth with no hypertrophic scar and hyperpigmentation. It was soft and elastic. The joints could move randomly. The histologic study showed the composite skin graft had a similar appearance as the normal skin.

CONCLUSIONAs for the treatment of wound, the composite skin graft with ADM is smooth and soft with good elasticity after transplantation, but it has no perspiration.

Adolescent ; Adult ; Child ; Child, Preschool ; Dermis ; transplantation ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Skin Transplantation ; methods ; Skin, Artificial ; Transplantation, Autologous ; Young Adult