Differences in related indicators after Toric intraocular lens implantation in cataract patients with different axial lengths / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the differences in visual recovery, corneal astigmatism, and rotation stability of Toric intraocular lens(TIOL)implantation in cataract patients with different axial lengths.METHODS: Retrospective analysis. A total of 132 patients(132 eyes)with age-related cataract and corneal astigmatism who underwent phacoemulsification cataract extraction combined with TIOL implantation in our hospital's ophthalmology department from February 2021 to September 2022 were selected. They were divided into two groups based on the axial length: the group with axial length ≤24mm(79 cases, 79 eyes)and the group with axial length >24mm(53 cases, 53 eyes). Compare the best corrected distance visual acuity(BCDVA), corneal astigmatism, and TIOL rotation between the two groups of patients at 3mo after surgery.RESULT: After 3mo of surgery, both groups of patients had improved BCDVA and significantly decreased corneal astigmatism compared to those before surgery(P<0.001). However, there was no difference in BCDVA and corneal astigmatism between the two groups(P>0.05), and there was no significant difference in TIOL rotation between the two groups [(5.24±3.72)° vs.(6.36±4.21)°, P=0.110].CONCLUSION: There is no significant difference in visual recovery, corneal astigmatism, and TIOL rotational stability after TIOL implantation in cataract patients with different axial lengths.

Clinical characteristics and comprehensive treatment of patients with cleidocranial dysplasia / 中华口腔医学杂志

Objective: To summarize the clinical characteristics of patients with cleidocranial dysplasia (CCD) and analyze their treatment methods. Methods: From January 2000 to December 2020, patients with CCD who completed comprehensive treatment in the Department of Orthodontics and the First Dental Clinic, School and Hospital of Stomatology, China Medical University were retrospectively analyzed. A total of 14 CCD patients [7 males and 7 females, aged (16.1±4.5) years] were collected. There were 153 impacted permanent teeth in this study. In addition to the teeth that needed to be extracted due to special conditions, 147 impacted teeth were pulled into the dentition using closed traction. Patients were divided into adolescent group (≥12 years and<18 years, 10 patients) and adult group (≥18 years, 4 patients). Failure rate of traction was compared between the two groups. Factors affecting the success rate of closed traction such as vertical position of teeth (high, middle and low) and horizontal position of the teeth (palatal, median and buccal) were analyzed. Results: The incidence of maxillary impacted teeth [69.3% (97/140)] was higher than that of mandibular impacted teeth [40% (56/140)]. The difference was statistically significant (χ2=24.22, P<0.001). The supernumerary teeth were mainly located in the premolar area 61.4% (21/44), and most of them were in the palatal region of the permanent teeth 95.5% (42/44). They were generally located at the same height or the occlusal side of the corresponding permanent teeth. The success rate of closed traction was 93.9% (138/147). The success rate in the adolescent group [98.2% (108/110)] was higher than that in the adult group [81.1% (30/37)], and the difference was significant (χ2=14.09, P<0.05). Failure after closed traction of 9 teeth was found totally, including 7 second premolars. The success rate of traction in impacted second premolars at different vertical (χ2=11.44, P<0.05) and horizontal (χ2=9.71, P<0.05) positions in alveolar bone was different significantlly. The success rates of the second premolars were high (15/16), middle (12/13), low (2/7), and lingual palatine (10/17), median (19/19), lip-buccal (0/0), respectively. Conclusions: The closed traction of impacted teeth in patients with CCD was effective, and the age was the main variable affecting the outcome. The success rate of traction in impacted second premolars located in low position vertically or in palatal position was low, which required close observation during treatment.

Role of DNMT3a in Hydroquinone-Induced Hematopoietic Stem Cell Toxicity / 中国实验血液学杂志

OBJECTIVE@#To investigate the regulatory effect and mechanism of DNA methyltransferase 3A (DNMT3a) in hydroquinone-induced hematopoietic stem cell toxicity.@*METHODS@#Cells (HSPC-1) were divided into 4 groups, that is A: normal HSPC-1; B: HQ-intervented HSPC-1; C: group B + pcDNA3 empty vector; D: group B + pcDNA3- DNMT3a. RT-qPCR and Western blot were used to detect the expression levels of DNMT3a and PARP-1 mRNA and protein, respectively. Cell morphology was observe; Cell viability and apoptosis rate of HSPC-1 were detected by MTT and flow cytometry, respectively.@*RESULTS@#Compared with group A, the expression levels of DNMT3a mRNA and protein in HSPC-1 of group B were decreased, while PARP-1 mRNA and protein were increased (P<0.05); there was no significant difference in the above indexes between group C and group B; compared with group B, the expression levels of DNMT3a mRNA and protein showed increased, while PARP-1 mRNA and protein were decreased significantly in cells of group D transfected with DNMT3a (P<0.05). Cells in each group were transfected with DNMT3a and cultured for 24 h, HSPC-1 in group A showed high density growth and mononuclear fusion growth, while the number of HSPC-1 in group B and C decreased and grew slowly. Compared with group B and C, the cell growth rate of group D was accelerated. The MTT analysis showed that cell viability of HSPC-1 in group B were lower than that of group A at 24 h, 48 h and 72 h (P<0.05); after transfected with DNMT3a, the cell viability of HSPC-1 in group D were higher than that of group B at 24 h, 48 h and 72 h (P<0.05). The apoptosis rate of cells in group B was significantly higher than that of group A (P<0.001), while the apoptosis rate in group D was lower than that of group B (P<0.001).@*CONCLUSION@#DNMT3a may be involved in the damage of hematopoietic stem cells induced by hydroquinone, which may be related to the regulation of PARP-1 activity by hydroquinone-inhibited DNMT3a.

Development and analysis of clinical prediction model of acupuncture and moxibustion treatment for stroke at recovery stage / 中国针灸

OBJECTIVE@#To develop the clinical prediction model of therapeutic effect in treatment with acupuncture and moxibustion for the patients with stroke at recovery stage under different conditions so as to provide a tool for predicting the therapeutic effect of acupuncture and moxibustion.@*METHODS@#A total of 1410 patients with stroke at recovery stage were collected from the Third Affiliated Hospital of Zhejiang Chinese Medical University from 2012 to 2019. The relevant data were extracted, i.e. sex, age, time of onset, neurological functional deficit score (NFDS) and acupuncture and moxibustion therapy. The difference of NFDS before and after treatment was adopted to evaluate the therapeutic effect in the patients. Using SPSS26.0 software and CART decision tree analysis, the clinical prediction model was developed.@*RESULTS@#The key variables in the prediction model of therapeutic effect in the patients with stroke at recovery stage under different conditions included age, time of onset, hypertension, cardiac disease, diabetes, TCM diagnosis, hemoglobin (HB), serum homocysteine (HCY) and acupuncture and moxibustion therapy. There were 12 main rules generated by the decision tree model, including 8 rules for predicting the improvements of therapeutic effect and 4 rules for predicting the absence of improvements (i.e. no change and deterioration). The accuracy rates of the model training set and test set were 80.0% and 72.8% respectively, the area under curve (AUC) of ROC was 0.797 and the model identification and classification results were satisfactory.@*CONCLUSION@#The clinical prediction model developed by CART decision tree analysis is high in accuracy for the prediction of the therapeutic effect in the patients with stroke at recovery stage under different conditions. Based on the therapeutic effect predicted in the hospital visit, the physicians may adopt the corresponding regimens of acupuncture and moxibustion therapy in patients.

Silencing DNMT1 Attenuates the Effect of WIF-1 Gene Promoter Methylation on the Biological Behavior of Chronic Myeloid Leukemia K562 Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of silencing DNA methyltransferase 1(DNMT1) to the methylation of the promoter of the tumor suppressor gene wnt-1 (WIF-1) in human chronic myeloid leukemia (CML) cells.@*METHODS@#DNMT1 siRNAi plasmid was constructed and DNMT1 siRNAi was transfected into CML K562 cells. RT-PCR and Western blot were used to detect the expression of DNMT1 gene and related protein, and methylation PCR was used to detect WIF-1 gene promoter methylation level. The trypan blue exclusion and MTT assay were used to detect the cell proliferation, flow cytometry were used to detect the cell apoptosis rate, colony formation assay was used to detect cell colony formation ability. Expression of Wnt/β- catenin and its downstream signaling pathway proteins were detected by Western blot after DNMT1 gene was silenced.@*RESULTS@#The expression level of DNMT1 mRNA and its related protein in the experimental group were significantly lower than those in the control group and negative control group (P<0.05). After 72 hours of successful transfection, the WIF-1 gene in the control group and negative control group were completely methylated, while in the experimental group, the methylation level significantly decreased. The results of MSP showed that the PCR product amplified by the unmethylated WIF-1 primer in the experimental group increased significantly,while by the methylated WIF-1 primer decreased significantly. After 48 h of transfection, the OD value, viable cell number and colony formation of the cells in experimental group were significantly lower than those in the negative control group and the control group (P<0.05). The apoptosis rate of the cells in experimental group was significantly higher than those in the negative control group and control group (P<0.05). The expression levels of β- actin, myc, cyclin D1 and TCF-1 in K562 cells in the experimental group were significantly lower than those in the negative control group and control group (P<0.05).@*CONCLUSION@#Silencing DNMT1 gene can inhibit the proliferation and promote the apoptosis of K562 cells. The mechanism may be related to reverse the hypermethylation level of the WIF-1 gene promoter, thereby inhibit the activity of the Wnt/β- catenin signaling pathway.

Research Models of the Nanoparticle-Mediated Drug Delivery across the Blood–Brain Barrier

Brain diseases and damages come in many forms such as neurodegenerative diseases, tumors, and stroke. Millions of people currently suffer from neurological diseases worldwide. While Challenges of current diagnosis and treatment for neurological diseases are the drug delivery to the central nervous system. The Blood–Brain Barrier (BBB) limits the drug from reaching the targeted site thus showing poor effects. Nanoparticles that have advantage of the assembly at the nanoscale of available biomaterials can provide a delivery platform with potential to raising brain levels of either imaging therapeutic drugs or imaging. Therefore, successful modeling of the BBB is another crucial factor for the development of nanodrugs. In this review, we analyze the in vitro and in vivo findings achieved in various models, and outlook future development of nanodrugs for the successful treatment of brain diseases and damages.

Construction of Matrine Solid Lipid Nanoparticle and Determination of the Entrapment Efficiency / 中国药学杂志

OBJECTIVE: To prepare matrine solid lipoid nanoparticle,establish preparating method and determine the encapshlation efficiency. METHODS: Matrine solid lipoid nanoparticle was prepared by microemulsion-probe ultrasonic method and its quality was evaluated by particle size, Zeta potential, microscopic morphology and in vitro release. The encapsulation efficiency of the carrier was measured by different methods and their effect was compared. RESULTS: The diameter of matrine solid lipoid nanoparticle was (116.7±2.6) nm and its Zeta potential was (-45±1.7)mV. Transmission electron micrographs showed that the solid lipoid nanoparticle was uniform in size and spherical. The in vitro release result suggested the carrier exhibited control release character. Dextran gel microcolumn centrifugation can effectively separate free drugs and carriers, and the measured encapsulation efficiency data has little difference in stability. CONCLUSION: Matrine solid lipoid nanoparticle is successfully prepared and their particle size, Zeta potential and in vitro release quality are evaluated.Dextran gel microcolumn method is effective in the measurement of matrine solid lipoid nanoparticle, providing a reliable reference for the determination of water-soluble drug encapsulation efficiency.

Correlation between social psychology and personality characteristics and treatment options for adult patients with skeletal malocclusion / 华西口腔医学杂志

OBJECTIVE@#This study aims to explore factors affecting the dental aesthetic social psychology of patients with skeletal malocclusion and to measure the relationship between the objective orthodontic requirements and the subjective treatment requirements of patients. This work provides a reference for doctors to measure patients' orthodontic treatment needs.@*METHODS@#Adult patients with skeletal malocclusion were chosen as the research object. Questionnaire survey was used to analyze factors influencing the psychosocial impact of dental aesthetics questionnaire (PIDAQ), index of orthodontic treatment need (IOTN), and Eysenck personality questionnaire-revised short scale for Chinese (EPQ-RSC). The relationship among PIDAQ, IOTN, EPQ-RSC, and treatment options was also evaluated.@*RESULTS@#Seventy-two valid questionnaires were collected from adult patients with skeletal malocclusion. 1) The PIDAQ scores significantly differed among different occupations (P0.05). People with low educational level were more likely to receive surgery if their psychosocial impacts of dental aes-thetics were serious. 5) The score of psychoticism scale of EPQ-RSC and the educa-tional level had a mutual influence on the PIDAQ score (P<0.01). Moreover, the neuroticism scale and AC self-assessment scores had a mutual influence on the PIDAQ score (P<0.05). However, this study did not find a correlation between personality traits and treatment options.@*CONCLUSIONS@#Many factors, such as personal natural conditions, subjective aesthetic evaluation of teeth, and psychosocial impacts of dental aesthetics, affect patients' treatment options. Personality characteristics can play a certain role in dental aesthetics social psychology.

Tissue Distribution of 14 Bioactive Components After Oral Administration of Gegen Qinlian Tang in Rats / 中国实验方剂学杂志

Objective:To investigate the tissue distribution of major bioactive components from Gegen qinlian Tang(GQT) in rats,and to reveal the mechanism for the efficacy of GQT by the tissue targeting of its bioactive ingredients in vivo. Method:After oral administration of GQT in rats,tissues were collected at different time points,including small and large intestine,liver,heart,spleen,lung,and kidney.Samples were prepared for determination of 14 bioactive components of GQT in tissue homogenate by HPLC-MS/MS.The chromatography separation was performed on an Agilent ZORBAX SB-C18 column(2.1 mm×100 mm,3.5 μm) with acetonitrile-0.1% formic acid in water for gradient elution.Electrospray ionization(ESI) was applied and operated in the positive ion mode.Meanwhile,naringin was used as the internal standard for determining. Result:HPLC-MS/MS for simultaneous determination of 14 components from GQT in tissue homogenate was developed and validated by specificity,calibration curves,recovery test,matrix effect,precision,accuracy,and stability.In the small intestine,the the area under the curve(AUC0-10 h) of major isoflavonoids(puerarin,3'-hydroxypuerarin,and daidzein) were 22 174.9,15 893.1,3 882.5 h·mg·L-1,major flavonoids(baicalein,wogonin,wogonoside,and baicalin) were 15 423.6,15 408.4,7 017.3,3 697.7 h·mg·L-1,and major alkaloid(berberine) was 2 544.0 h·mg·L-1,respectively.The distribution of these ingredients in the small intestine was significantly higher than that in other tissues. Conclusion:The effective ingredients of GQT are mainly distributed in the intestinal tissues,which speculates that the anti-inflammatory and antidiarrheal activities of GQT may be related to its targeting in the intestine.

Difference of Copper ，Lead，Cadmium，Mercury and Arsenic in the Single Decoction and Combined Decoction of Huangqi Jianzhong Decoction / 中国药房

OBJECTIVE： To study the difference of the contents of copper， lead， cadmium， mercury and arsenic in the single decoction and combined decoction of Huangqi jianzhong decoction （containing Astragali radix， Cinnamomi ramulus， Paeoniae radix alba， prepared Glycyrrhiza uralensis， Zingiberis rhizoma recens， Jujubae fructus）， and to provide reference for safe use of TCM in clinic. METHODS： Samples of medicinal materials， single decoction and combined decoction were prepared from different medicinal materials； the contents of copper， lead， cadmium， mercury and arsenic in various samples were determined by atomic absorption spectrophotometry， which were compared with the limits of copper （＜20 mg/kg）， lead （＜5 mg/kg）， cadmium （＜0.3 mg/kg）， mercury （＜0.2 mg/kg） and arsenic （＜2 mg/kg） content stated in 2015 edition of Chinese Pharmacopeia and Green Trade Standards of Importing Exporting Medicinal Plants Preparations. The difference of 5 elements contents were compared between single decoction and combined decoction. RESULTS： Among the 6 medicinal materials， the cadmium content of Cinnamomi ramulus and Zingiberis rhizoma recens exceeded the standard， 0.32， 0.74 mg/kg， respectively （copper， lead， mercury and arsenic all met the requirements）， and the 5 elements content of other medicinal materials all met the requirements； the contents of copper， lead， cadmium， mercury and arsenic in the single and combined decoction meet the requirements； compared with the medicinal materials， the contents of copper， lead， cadmium， mercury and arsenic in the single decoction were lower （P＜0.01）； compared with mixture of single decoction， the contents of copper and mercury in combined decoction were lower （P＜0.01）， while the contents of lead， cadmium and arsenic in the decoction were higher （P＜0.01）. CONCLUSIONS： For Huangqi jianzhong decoction， combined decoction can reduce the dissolution of copper and mercury， and increase the dissolution of lead， cadmium and arsenic. The possible reason is that the interaction of various components in the co-decoction process changes the solubility of copper， lead， cadmium， mercury and arsenic.

The study of college students’ physical exercise behavior phase and process of change based on the Transtheoretical model / 中华疾病控制杂志

Objective To analyze the stage characteristics in the exercise behavior improvement of college students and explore the role of Process in the exercise behavior change based on the transtheoretical model, providing basis for the stage-matched intervention for the exercise behavior of college students. Methods There were 932 students who completed the questionnaires, from 5 universities in Shanxi Province were selected by using a stratified random cluster sampling method. Descriptive analysis was used to describe the exercise behavior of college students. Variance analysis and multivariate Logistic regression model were used to analyze the difference of the process of with stage of change among college students’ physical exercise. Multivariate variance analysis was used to analyze how personal characteristics affect process of change. Results Among all participants, 89.4% students knew the importance of physical exercise, and 29.4% students were satisfied with their physical exercise condition. The distribution of students’ physical exercise stage showed an inverted U-shape with left-side peak, and there was a significant difference between gender( 2=54.657, P<0.001). There were significant stage characteristics in the process of students' exercise behavior, gender had a significant main effects on mutual aid relation(F=7.400, P=0.07)and conscious control (F=7.778, P=0.005), gender and grade had interaction effects on social release (F=3.614, P=0.013). Conclusions The college students' exercise behavior showed the characteristics of “knowing but not to do”, which conformed to the Transtheoretical model. It is essential to develop targeted phased exercise intervention strategies according to the relationship between change of phase and change of procedure.

Glucose metabolism modeling of diabetes patients with different intensities of aerobic exercise: an in silico study / 生物医学工程学杂志

Exercise is vital for diabetics to improve their blood glucose level. However, the quantitative relationship between exercise modes (including types, intensity, time, etc.) and the blood glucose is still not clear. In order to answer these questions, this paper established a blood glucose metabolic model based on ordinary differential equation method. Furthermore, a silico method was adopted to study the effects of different aerobic exercise intensities (light, moderate and vigorous) on blood glucose and optimal strategies of insulin infusion for type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Additionally, the universality of proposed model and insulin infusion strategies was verified based on 1 000 virtual diabetes patients' simulation. The experimental results showed that: (1) Vigorous-intensity aerobic exercise may result in hypoglycemia ( 6.11 mmol/L) period, however, its overall blood glucose risk index (BGRI) was lower. (2) Insulin dosage of the optimized strategies decreased by 50% and 84% for T1DM and T2DM when they did moderate intensity exercise. As for light intensity exercise, the dosage of insulin was almost the same as they didn't do exercise, but BGRI decreased significantly. (3) The simulations of 1 000 virtual diabetic patients manifested that the proposed model and the insulin infusion strategies had good universality. The results of this study can not only help to improve the quantitative understanding about the effects of aerobic exercise on blood glucose of diabetic patients, but also contribute to the regulation and management of blood glucose in exercise mode.

Effects of caloric restriction on the expression of lipocalin-2 and its receptor in the brown adipose tissue of high-fat diet-fed mice

Obesity causes inflammation and impairs thermogenic functions in brown adipose tissue (BAT). The adipokine lipocalin 2 (LCN2) has been implicated in inflammation and obesity. Herein, we investigated the protective effects of caloric restriction (CR) on LCN2-mediated inflammation and oxidative stress in the BAT of high-fat diet (HFD)-fed mice. Mice were fed a HFD for 20 weeks and then either continued on the HFD or subjected to CR for the next 12 weeks. CR led to the browning of the white fat-like phenotype in HFD-fed mice. Increased expressions of LCN2 and its receptor in the BAT of HFD-fed mice were significantly attenuated by CR. Additionally, HFD+CR-fed mice had fewer neutrophils and macrophages expressing LCN2 and iron-positive cells than HFD-fed mice. Further, oxidative stress and mitochondrial fission induced by a HFD were also significantly attenuated by CR. Our findings indicate that the protective effects of CR on inflammation and oxidative stress in the BAT of obese mice may be associated with regulation of LCN2.

Clinical features and diagnosis of childhood leukoencephalopathy with cerebral calcifications and cysts in four cases / 中华儿科杂志

Objective@#To investigate the clinical features and diagnostic bases of childhood leukoencephalopathy with cerebral calcifications and cysts (LCC).@*Methods@#The clinical data involving manifestations and laboratory examinations of 4 children with LCC admitted to Beijing Children's Hospital Affiliated to Capital Medical University from 2012 to 2017 were retrospectively summarized. Each patient had a follow-up visit ranging from 4 months to 5 years and 9 months after initial examination.@*Results@#Patients consisted of 2 males and 2 females, whose age of onset was respectively 2 years and 9 months, 6 years and 2 months, 7 years and 10 months, and 5 years and 1 month. The main clinical symptoms of these cases included headache, dizziness, partial seizure and claudication, and two of these cases had insidious onset. Cerebral calcifications and cysts with leukoencephalopathy were detected by neuroimaging in all patients. In addition, multifocal microhemorrhages and calcifications were observed by magnetic susceptibility-weighted imaging (SWI) series in 3 patients. Brain biopsy performed on 1 case disclosed a neuronal reduction in the cerebral cortex, loosening of focal white matter, multifocal lymphocyte infiltration, fresh hemorrhages, and gliosis, as well as angiomatous changes of blood vessels with hyalinized thicken-wall, stenotic or occlusive lumina and calcification deposits. The compound heterozygous mutations of n.*10G>A and n.82A>G in SNORD118 were identified in 1 case by target-capture next-generation sequencing. Sanger sequencing verified that the variant n.*10G>A was a novel mutation and it was of paternal-origin, while the variant n.82A>G was of maternal-origin, which had already been reported to be pathogenic to LCC. Follow-up study had shown continued partial seizure in 1 case and remissive claudication in another, while the remaining 2 cases had a relatively favorable outcome without obvious neurological symptoms at present time.@*Conclusions@#The clinical manifestations of LCC are nonspecific, and the onset of the disease tends to be insidious. The triad neuroimaging findings of cerebral calcifications, cysts and leukoencephalopathy are essential to the diagnosis of the disease, and the signals of microhemorrhages revealed by SWI series provide another eloquent reference for the diagnosis. As biopsy is invasive and usually unavailable in the early stage, gene assessment, instead of pathological data, should be the gold standard in the diagnosis of LCC.

The measurement of hemoglobin A1c and its application in diabetes mellitus diagnosis / 中华检验医学杂志

Although it has been widely used in the diagnosis and management of diabetes abroad , the application of hemoglobin A 1c ( HbA1c ) test is restricted due to the difference of test ability between various level laboratories in China.The methods, interference and standardization of HbA 1c are still worthy of continuous paying attention by laboratory physicians . How to choose the most economical and efficient method, and how to provide accurate and reliable results for patients are the priorities which can promote the application of HbA1c in diabetes diagnosis and management in China.

Expression of Astrocyte,Neuron,and Proinflammatory Cytokines Derived from Frontal Cortex of Methamphetamine Dependent rats after Gastrodin Administration / 昆明医科大学学报

Objective To observe the curative mechanism and effect of neurotoxicity injury induced by methamphetamine (MA) and the neuroprotective effects of gastrodin interfered. Whether the expression of astrocyte and proinflammatory cytokines has contributed to the effects of gastrodin.Methods 48 healthy male SD rats were randomly divided into three groups: control group (Daily intraperitoneal injection of saline for 8 weeks),MA group (A dose of 10 mg/kg MA was administered every day for four weeks,then given daily intraperitoneal injection with 10 mg/kg saline for 4 weeks) and gastrodin group (A dose of 10 mg/kg MA was administered every day for four weeks,then given daily intraperitoneal injection with 10 mg/kg gastrodin for 4weeks) . The behavioral changes of rats were measured by conditioned place preference ( CPP) and sterotyped behavior ( SB) induced by methamphetamine. Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein (GFAP) and NEUN in rat frontal cortex.The expression of IL－6 and TNF－α were detected by quantity RT－PCR and westrn bloting.Results Compa MA depndent 4 weeks group with control group, the scores of sterotyped behavior of MA depndent groups had signficantly increased (P＜0.01) . Comparing MA depndent 4 weeks group with MA depndent 4 weeks+gastrodin group, the scores of sterotyped behavior of MA dependent 4 weeks group had obviously decreaseed (P＜0.01) . Compared with the control group, the expression of GFAP of MA dependent 4 weeks group decreased and the expression of NEUN increased. Compared MA dependent 4 weeks group with control group, the expression of IL－ 6 and TNF－α increased (P＜0.01) . Compared MA dependent 4 weeks+gastrodian group with MA dependent 4 weeks group, the expression of TNF－α and IL－6 significantly reduced (P＜0.01) . Conclusion The neurological damage induced by methamphetamine might be related to the activation of astrocytes and the high expression of inflammatory cytokines including IL－6 and TNF－α. Gastrodin could abate the neurological injury of methamphetamine dependence via reducing the activation of astrocytes and decreasing the expression of IL－6 and TNF－α.

Chondrogenic Potential of Dedifferentiated Rat Chondrocytes Reevaluated in Two- and Three-Dimensional Culture Conditions

For the cartilage repair, the cell sources currently adopted are primarily chondrocytes or mesenchymal stem cells (MSCs). Due to the fact that chondrocytes dedifferentiate during 2-dimensional (2D) expansion, MSCs are generally more studied and considered to have higher potential for cartilage repair purposes. Here we question if the dedifferentiated chondrocytes can regain the chondrogenic potential, to find potential applications in cartilage repair. For this we chose chondrocytes at passage 12 (considered to have sufficiently dedifferentiated) and the expression of chondrogenic phenotypes and matrix syntheses were examined over 14 days. In particular, the chondrogenic potential of MSCs was also compared. Results showed that the dedifferentiated chondrocytes proliferated actively over 14 days with almost 2.5-fold increase relative to MSCs. Moreover, the chondrogenic ability of chondrocytes was significantly higher than that of MSCs, as confirmed by the expression of a series of mRNA levels and the production of cartilage extracellular matrix molecules in 2D-monolayer and 3-dimensional (3D)-spheroid cultures. Of note, the significance was higher in 3D-culture than in 2D-culture. Although more studies are needed such as the use of different cell passages and human cell source, and the chondrogenic confirmation under in vivo conditions, this study showing that the dedifferentiated chondrocytes can also be a suitable cell source for the cell-based cartilage repair, as a counterpart of MSCs, will encourage further studies regarding this issue.

Pharmacokinetic characteristics of fourteen main components of Gegen Qinlian Decoction in rats / 中国中药杂志

A specific and selective UPLC-MS/MS method was developed and validated for the simultaneous determination of isoflavonoids(3'-hydroxy puerarin, puerarin, daidzin, daidzein, genistin, genistein), flavonoids (baicalin, baicalein, wogonoside, wogonin, liquiritin)and alkaloids(berberine, jatrorrhizine, palmatine)(14 bioactive compounds) of Gegen Qinlian Decoction(GQD) in plasma. The pharmacokinetics characteristics of 14 bioactive compounds were study after oral administration of GQD at a single dose to rats. Prednisolone was used as the internal standard of liquiritin, and naringin was used as the internal standard of the other thirteen analytes. After the plasma samples were processed by precipitation protein method, the constituents and internal standards were gradient eluted by using a Zorbax SB-18 column with a mobile phase of acetonitrile(A) and 0.1% formic acid aqueous solution(B) using a gradient elution of 0-2.5 min, 15%-30% A; 2.5-3.5 min, 30%-35% A; 3.5-5.0 min, 35%-40% A; 5.0-9.0 min, 40%-60% A; 9.0-11.0 min, 60%-15% A, and the flow rate was 0.4 mL·min⁻¹. The auto sampler was conditioned at 25 °C and the sample injection volume was 5 μL. A mass spectrometry was applied with electrospray ionization (ESI) ion source in the positive and negative ion multiple reaction monitoring(MRM) mode. All pharmacokinetic parameters were processed by non-compartmental analysis with DAS 3.2.2 software. The results showed that the linear correlation coefficient of the 14 components were all greater than 0.99, indicating that the method had good linearity in their respective concentration ranges. Post-preparative stability (25 °C, 24 h), short-term stability(25 °C, 12 h), long-term stability (-20 °C, 7 d), and freeze and thaw stability (3-cycles) of the fourteen constituents were examined to evaluate the stability of methodology. The results of the inner and inter-day relative standard deviations were both less than 10%, indicating legitimate precise and accuracy to the requirement of biological sample analysis. The assay method is proved to be sensitive, accurate and convenient. It can be applied to the pharmacokinetic study of the fourteen analytes. The kinetic parameters of the related drugs were calculated according to the blood concentration of the 14 components. The results showed that the MRT0-t of the isoflavones and flavonoids was 7.5-11.8 h, T1/2z were mainly in 11.0-29.7 h, and the AUC0-t flavonoids were larger than the isoflavones. The MRT0-t of alkaloids were between 4.3-7.2 h, T1/2z were 1.0-5.0 h, AUC0-t were less than flavonoids and isoflavones. The results suggest that flavonoids and isoflavones have a high concentration of blood and long time of action, which are beneficial to the anti-inflammatory and antipyretic effects. The concentration of alkaloids in the body is low and the time of action is short, and it may play its bacteriostasis in the intestinal tract.

Cilostazol attenuates kainic acid-induced hippocampal cell death

Cilostazol is a selective inhibitor of type 3 phosphodiesterase (PDE3) and has been widely used as an antiplatelet agent. Cilostazol mediates this activity through effects on the cyclic adenosine monophosphate (cAMP) signaling cascade. Recently, it has attracted attention as a neuroprotective agent. However, little is known about cilostazol's effect on excitotoxicity induced neuronal cell death. Therefore, this study evaluated the neuroprotective effect of cilostazol treatment against hippocampal neuronal damage in a mouse model of kainic acid (KA)-induced neuronal loss. Cilostazol pretreatment reduced KA-induced seizure scores and hippocampal neuron death. In addition, cilostazol pretreatment increased cAMP response element-binding protein (CREB) phosphorylation and decreased neuroinflammation. These observations suggest that cilostazol may have beneficial therapeutic effects on seizure activity and other neurological diseases associated with excitotoxicity.

Atorvastatin pretreatment attenuates kainic acid-induced hippocampal neuronal death via regulation of lipocalin-2-associated neuroinflammation

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.