The striatum is involved in diverse behaviors which depend on intact dopaminergic innervation. Recent electrophysiological studies have revealed that dopamine alters both voltage dependent conductances and synaptic transmission, resulting in state dependent modulation of target cells. This review makes clear predictions about how dopamine should alter the responsiveness of striatal neurons to extrinsic excitatory synaptic activity.

Abstract: Objective　To investigate the diagnostic efficacy of rifampin-resistant real-time fluorescent quantitative nucleic acid amplification detection technology (GeneXpert MTB/RIF) in bronchoalveolar lavage fluid (BALF) combined with peripheral blood tuberculosis infection T cell spot test (T-SPOT) and tuberculosis antibody (TB-Ab) in smear-negative pulmonary tuberculosis. Methods　The clinical data of 114 cases of clinically diagnosed smear-negative pulmonary tuberculosis, 80 cases of non-tuberculous pulmonary diseases and 22 cases of smear-positive pulmonary tuberculosis in our hospital from January 2019 to January 2021 were retrospectively analyzed. The detection results of peripheral blood T-SPOT, TB-Ab and BALF GeneXpert in the three groups were analyzed. The sensitivity, specificity, negative predictive value, positive predictive value, false negative rate, false positive rate and Youden index of the three detection methods were compared. The differences in the positive detection rate of smear-negative pulmonary tuberculosis between the separate detection and the combined detection of the three methods were compared. The receiver operating characteristic curve (ROC) was performed to calculate the area under the curve (AUC). Results　The sensitivity of BALF GeneXpert and peripheral blood T-SPOT and TB-Ab was 66.91%, 80.88% and 90.44%, respectively. The specificity was 98.75%, 73.75% and 41.25%, respectively; the diagnostic coincidence rates were 78.70%, 78.24% and 72.22%, respectively, which were higher than 70.00%. In the smear-negative pulmonary tuberculosis group, the positive detection rates of these three methods in the smear-negative pulmonary tuberculosis group were 63.15%, 79.82% and 90.35%, respectively, and the differences were statistically significant compared with those in the non-tuberculosis pulmonary disease group (all P<0.01). The positive detection rate of the three combined methods in the smear-negative pulmonary tuberculosis group was 96.49 %, which was significantly higher than that of TB-GeneXpert method and T-SPOT, and the differences were statistically significant (χ2=37.283, P<0.01; χ2=13.612, P<0.01); the Youden index of combined detection was significantly higher than that of single detection, and the AUC of combined detection was 0.977, which was significantly higher than that of single detection. Conclusion　BALF GeneXpert combined with peripheral blood T-SPOT and TB-Ab can significantly improve the diagnostic rate of bacterial-negative pulmonary tuberculosis, providing a strong basis for guiding clinical treatment.

OBJECTIVEIn the recent twenty years, the diaphragmatic contraction, relaxation functions and electric activity have been explored through electromyography (EMG) and transdiaphragmatic pressure (Pdi) determination. But these techniques required some complex and expensive instruments, so the diagnosis and treatment of children's diaphragmatic fatigue have not been well evaluated. The present study explored the diagnosis of children's diaphragmatic fatigue through measuring ribcage-abdomen motion and analyzed its asynchrony.

METHODSFifty-three children (male 37, female 16, and age rage from 1 months to 9 years) with respiratory rate > 30 breaths/min, heart rate > 110 beats/min, and respiratory dysfunction had asynchronized ribcage-abdomen motion showed by impedance respirograph (IRG). The authors observed whether ribcage-abdomen motion was synchronic and calculated M levels (staggered peak time/total duration of the breathing cycle). The ribcage and abdomen outputs were displayed on vertical (for rib cage) and horizontal (for abdomen) axes of X-Y instrument. In addition, the change of respiratory frequency and heart rate was observed and arterial blood-gas analysis was also performed.

RESULTS(1) M levels in one-dimensional IRG were positively correlated with alpha angle in two-dimensional IRG (r = 0.956, P < 0.001). Asynchronized respiratory motions could be divided into three types. type I showed completely contra-directional movements of respiration, M levels for (48.1 +/- 4.4)%, an irregularly clockwise loop in the two dimensional IRG, and alpha angle for (138.3 +/- 15.0) degrees. In type II, one dimensional IRG showed displaced peak of the chest and abdomen motion curves, M levels were (16.5 +/- 4.7)%, two dimensional IRG was displaced in a counterclockwise direction, and alpha angle was (55.3 +/- 10.8) degrees. In type III, abdominal motion curve of one dimensional IRG had double peaks, M levels were 0, two dimensional IRG was presented as 8-shaped double circles, alpha angle was (41.3 +/- 3.8) degrees; (2) pH levels in the patients with type I and type II diaphragmatic fatigue were significantly lower, and PCO(2) levels were significantly higher than those with type III or in the normal subjects (P < 0.001 for all), but there was no statistically significant difference between type III and the normal subjects (P > 0.05); (3) Both of respiratory rate and heart rate in type I, type II and type III were higher than those in the normal subjects (all P < 0.001), and the differences among the three types were significant (P < 0.001 for all); (4) Both M levels and alpha angle were negatively correlated with pH levels (r = -0.514, P < 0.001 and r = -0.497, P < 0.001), while positively correlated with PCO(2) levels (r = 0.672, P < 0.001 and r = 0.625, P = 0.01).

CONCLUSIONS(1) IRG can be reliably used to diagnose children's diaphragmatic fatigue. This technique is simple and easy to perform and non-invasive. It is therefore worthy of recommending for further clinical investigations. (2) According to the characteristics of IRG, diaphragmatic fatigue can be divided into three types. (3) The development of children's diaphragmatic fatigue has a series of characteristic changes. (4) To avoid the patients suffering from respiratory failure, it is the key time to adopt the policies of prevention and treatment when IRG shows signs of type III diaphragmatic fatigue.

Child ; Child, Preschool ; Diaphragm ; physiopathology ; Fatigue ; classification ; diagnosis ; Female ; Humans ; Infant ; Male ; Respiration ; Respiratory Function Tests ; methods

The study reports the detection of neuroprotective effect of 10 kinds of coumarin derivatives and explores their possible mechanism. MTT method was used to screen the neuroprotective effect of 10 coumarin derivatives on neurotoxic agents (Aβ25-35 and rotenone) or OGD (oxygen-glucose deprivation). A compound with better protective effect was obtained. Then the effect of this compound on neurotoxic agents on PC12 was detected by the morphological observation. Furthermore, the effect of compound 3 on microglia with lipopolysaccharide (LPS) induced inflammation was detected. And the inflammatory factor was tested. Finally, direct free radical scavenging ability was detected. Compound 3 was found to be the best compound through three neurons toxic models. Not only compound 3 ameliorated cell viability reduced by three neurons toxic models, but also significantly inhibited the production of inflammatory factor (TNF-α and IL-1β). And its free radical scavenging ability is very good, especially the effect on superoxide anion, which is comparable with vitamin C. The significant scavenging effect of compound 3 on superoxide anion might be the mechanism of the neuroprotection. Compound 3 as a potential neural cell protective agent merits further investigation.
Animals ; Coumarins ; chemistry ; Free Radical Scavengers ; chemistry ; Inflammation ; Microglia ; drug effects ; Neurons ; drug effects ; Neuroprotective Agents ; chemistry ; PC12 Cells ; Rats

AIMTo investigate the effect of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener (KATPCO), on astrocyte glutamate uptake activity. The mechanism of action involved was also examined.

METHODSPrimary cultures of astrocytes were prepared from cerebral cortexes of 1 to 2 days old Sprague-Dawley rats. Cultures were preincubated with iptakalim of various concentrations with the absence or presence of 6-hydroxydopamine (6-OHDA, 50 micromol x L(-1)). Then, the cells were treated with pinacidil (10 micromol x L(-1), K+ channel opener) instead of iptakalim and pretreated with glibenclamide (20 micromol x L(-1), ATP-sensitive K+ channel inhibitor) before pinacidil or iptakalim was added into the medium so that the mechanism of action of iptakalim could be analysed. Astrocyte glutamate uptake activity was determined by intracellular concentration of 3H labeled D,L-glutamate, using isotope techniques.

RESULTSBoth iptakalim and pinacidil were shown to increase glutamate uptake activity of astrocytes and reverse inhibitory effect induced by 6-OHDA. But the increased and reversed effects of iptakalim or pinacidil on astrocytic glutamate uptake were found to be completely antagonized by glibenclamide.

CONCLUSIONThese data indicated that iptakalim can enhance astrocytic glutamate uptake activity due to its K+ channel opening properties and lessen glutamate excitotoxicity. Iptakalim may be useful for the therapy of Parkinson's disease.

Animals ; Animals, Newborn ; Astrocytes ; drug effects ; metabolism ; Cells, Cultured ; Cerebral Cortex ; cytology ; Glutamates ; metabolism ; Glyburide ; antagonists & inhibitors ; Neuroprotective Agents ; pharmacology ; Oxidopamine ; antagonists & inhibitors ; Pinacidil ; pharmacology ; Propylamines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasodilator Agents ; pharmacology

Objective To investigate the stimulative effects of CollagenⅠon the increased adhesion of rabbit bone marrow stromal cells (BMSCs), cytoskeleton actin organization and intracellular free Ca~(2+) concentration. Methods The third generation BMSCs isolated from mature rabbits were cultured at different initial concentrations on cover-slice coated by collagenⅠin RPMI1640 containing 10% fetal calf serum, and cultured on the same kind of cover-slice untreated with collagenⅠas control. The cells adhesive behavior at different times was assessed. Cellular actin organization was described as either typeⅠor typeⅡcells. In general, typeⅠcells are round and represent a preliminary stage of actin assembly, while typeⅡcells are elongated with organized actin fiber network. At the same time intracellular free Ca~(2+) concentration was measured by using calcium fluorescent probe Fluo-3/AM and laser confocal microscope. Results We found more typeⅡcells in BMSCs cultured with collagen typeⅠsix hours after culture than in the control group. At 12 hours 89% of the BMSCs were typeⅡcells, while only 55% were typeⅡcells in the control group. This indicated active cellular actin organization after being modified by collagen typeⅠ. We also found that the BMSCs cultured with collagen typeⅠincreased intracellular free Ca~(2+) concentration in monolayer culture. Conclusions CollagenⅠis effective in promoting the cellular adhesion, which suggests that a kind of internal relationship or cross-talk may exist between cellular actin organization, intracellular free Ca~(2+) concentration and cell adhesion. Further study, however, is needed.

OBJECTIVETo observe the effect of Gegen Qinlian Decoction (GQD) in combination with short-term intensive insulin treatment on type 2 diabetes mellitus (T2DM) of dampness-heat syndrome and its influence on dosage of insulin used.

METHODSThe GQD group (n = 14) was treated by GQD and insulin, while the conventional group (n = 16) was given insulin intensive treatment alone.

RESULTSIn the GQD group, the treatment was markedly effective in 5 patients, effective in 6 and ineffective in 3, the total effective rate being 78.6%, much better than that in the conventional group (2, 7, 7 and 56.3% respectively, u = 2.58, P < 0.01). And it took less time for controlling blood glucose (BG) in the GQD group (4.54 +/- 0.50 days) than that in the conventional group (5.31 +/- 0.57 days, P <0.01); furthermore, by the end of the treatment course, as compared with that at the time just after BG being controlled, the daily average insulin dosage used in the GQD group reduced by 9.07 +/- 6.51 U, while it was only 4.38 +/- 5.94 U in the conventional group, showing significant difference between them (P < 0.05).

CONCLUSIONBased on short-term insulin intensive treatment, the combined using of GQD could reduce the dosage of insulin used and shows better clinical curative effect for patients with T2DM of dampness-heat syndrome.

Adult ; Diabetes Mellitus, Type 2 ; drug therapy ; Diagnosis, Differential ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Insulin ; therapeutic use ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy

OBJECTIVETo probe into the establishing method and the evaluating system for rat model of ischemic stroke with qi deficiency and blood stasis syndrome (QDBS).

METHODSA rat model of ischemic stroke of QDBS was established by continual exhaustive swimming followed with middle cerebral artery occlusion (MCAO), and evaluated by analyzing the changes of exterior signs, tongue figure, hemorrheologic characters and brain histomorphology in the model rats.

RESULTSThe model rats showed a state of QDBS in the course of continual exhaustive swimming, such as slower weight gain, postponed food intake, darker tongue and longer sublingual veins; and presented the characteristics of cerebral ischemia with QDBS syndrome after MCAO, they were inactive, weak, and hemiplegic, with dark purple tongue and longer blue sublingual veins. Moreover, hemorrheologic examinations showed blood hyperviscosity and high platelet aggregation rate, and histomorphologic examinations showed a special figure of ischemic changes.

CONCLUSIONContinual exhausting swimming followed by MCAO is a method for establishing a rat model of ischemic stroke with QDBS syndrome, and its evaluating system could be constituted by multiple criteria, including exterior signs, tongue figure, hemorrheologic and histomorphologic indexes, etc.

Animals ; Brain Ischemia ; Diagnosis, Differential ; Disease Models, Animal ; Male ; Medicine, Chinese Traditional ; Qi ; Rats ; Rats, Sprague-Dawley ; Stroke ; Yang Deficiency

BACKGROUNDbevacizumab is a humanized recombinant vascular endothelial growth factor (VEGF) monoclonal antibody, which specifically binds to VEGF and inhibits tumor cell growth, proliferation and metastasis. We aimed to investigate the safety and pharmacokinetics of bevacizumab in Chinese patients with advanced cancer.

METHODSThirty-nine Chinese patients with metastatic or relapsed cancers who failed prior therapy were enrolled in this phase I study of bevacizumab. Bevacizumab was infused by a calculated pump at doses from 5 mg/kg to 15 mg/kg in 90 minutes. Patients underwent serial pharmacokinetic evaluations. Patients that received at least one infusion of bevacizumab were included in the safety study.

RESULTSThirty-five patients finished all 5 infusions following protocol. One patient withdrew after 3 infusions due to grade 3 proteinuria. Common adverse events possibly related to the study drug were proteinuria (17/39, 43.6%), hypertension (13/39, 33.3%), gingival bleeding (7/39, 17.9%), epistaxis (6/39, 15.4%), pharyngeal inflammation (6/39, 15.4%), fatigue (6/39, 15.4%) and stomatitis (4/39, 10.3%). Bevacizumab pharmacokinetics was linear within the range of 5 mg/kg q2w--10 mg/kg q2w and 15 mg/kg q3w. CL (clearance), Vd (volume of distribution at elimination) and Vss (volume of distribution at steady state) were similar after single and multiple doses at 5, 10 and 15 mg/kg.

CONCLUSIONSBevacizumab is well tolerated in Chinese patients. No unexpected adverse events were observed. There is no racial difference in the pharmacokinetics.

Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal ; adverse effects ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Asian Continental Ancestry Group ; Bevacizumab ; Female ; Humans ; Male ; Middle Aged ; Neoplasms ; drug therapy

OBJECTIVETo explore the effect of Osteoking on bone mineral density (BMD) and serum Dickkopf-1 (DKK-1) protein levels in rabbits with osteoporotic fracture (OPF).

METHODSTotally 45 female Japanese big-ear rabbits were randomly divided into the treatment group, the model group, and the blank control group (as the control group), 15 in each group. Bilateral ovaries were ectomized for 24 weeks in the treatment group and the model group. Their left radial factures were induced after confirmed osteoporosis. Rabbits in the treatment group were administered with Osteoking by gastrogavage, once per two days. Equal volume of normal saline was given to rabbits in the model group. The general BMD and serum DKK-1 protein levels were detected before ovariectomy, at week 24 and 48 after ovariectomy.

RESULTSThere was significant difference in the general BMD at week 24 after ovariectomy between the model group and the control group, and it was lower in the model group. Compared with the model group, the general BMD significantly increased and serum DKK-1 protein levels significantly decreased in the treatment group after intervention. Serum DKK-1 protein levels were significantly lower after intervention than before intervention in the treatment group.

CONCLUSIONOsteoking could improve the BMD of OPF rabbits, and reduce their serum DKK-1 protein levels as well.

Animals ; Bone Density ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Osteoporosis ; Osteoporotic Fractures ; drug therapy ; metabolism ; Ovariectomy ; Rabbits