Mechanism of Traditional Chinese Medicine in Prevention and Treatment of Parkinson's Disease：A Review / 中国实验方剂学杂志

Parkinson's disease （PD） is a progressive chronic neurodegenerative disorder with a complex pathogenesis involving oxidative stress， neuroinflammation， mitochondrial dysfunction， and other factors. Currently， the clinical treatment of PD mainly includes levodopa， dopamine receptor agonists， monoamine oxidase B inhibitors， catechol-O-methyltransferase inhibitors， and anticholinergic drugs， but there is a lack of disease-modif g therapies that can definitively improve disease progression. According to the understanding of traditional Chinese medicine （TCM）， PD is characterized by asthenia in origin and sthenia in superficiality. It is primarily caused by liver-kidney Yin deficiency， Qi-blood insufficiency， and closely related to wind， fire， phlegm， and blood stasis. Numerous clinical practices have shown that TCM has significant clinical value in the prevention and treatment of PD， the management of motor and non-motor symptoms， and the neuroprotection of dopaminergic neurons. The underlying mechanisms of TCM include antioxidative stress， anti-neuroinflammation， and regulation of mitochondrial dysfunction. This article categorized and summarized the pathogenesis of PD， systematically elucidated the pharmacological actions and molecular mechanisms of TCM monomer extracts and compounds in the prevention and treatment of PD， and provided the latest clinical research progress， aiming to provide references for the development and clinical use of TCM for PD.

Mechanism of Dendrobium huoshanense Polysaccharide Against Neuroinflammation in Parkinson's Disease Model： Based on NLRP3 Inflammasome / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Dendrobium huoshanense polysaccharide （DHP） against inflammatory damage of neurons in Parkinson's disease （PD） model. MethodSH-SY5Y cells were randomized into blank group， model group， and DHP group. The survival rate of cells was measured by thiazole blue（MTT） assay， and the levels of lactate dehydrogenase （LDH）， reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） were measured by colorimetric analysis. BV-2 microglia were classified into blank group， model group， DHP group， and MCC950 group （positive control group）， and enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. The expression of NOD-like receptor protein 3 （NLRP3）， adaptor protein apoptosis-associated dot protein （ASC）， cysteine aspartic protease-1 （Caspase-1）， and IL-1β was measured by Western blot. A total of 50 C57BL/6 mice were randomized into blank group， model group， DHP low-dose （100 mg·kg-1） group， DHP equivalent-dose （350 mg·kg-1） group， and MCC950 group （positive control group）， 10 mice in each group. The motor balance and coordination of C57BL/6 mice were observed by beam walking test， tail suspension test and rotarod test. The levels of Iba-1 and tyrosine hydroxylase （TH） were detected by immunofluorescence staining. The damage of dopaminergic neurons in the substantia nigra was detected by FJB staining. The levels of inflammatory factors such as IL-1β， IL-18， and TNF-α in mouse midbrain tissues were detected by ELISA and the protein levels of NLRP3， ASC， Caspase-1， and IL-1β protein were measured by Western blot. ResultCompared with the blank group， the SH-SY5Y model group showed decreased cell survival， increased levels of LDH， ROS， and MDA （P<0.05）， and decreased levels of SOD （P<0.05）. Compared with the model group， the DHP group demonstrated increased cell survival， decreased levels of LDH， ROS， and MDA （P<0.01）， and increased level of SOD （P<0.01）. Compared with the blank group， BV-2 model group had high levels of IL-1β， IL-18， and TNF-α （P<0.05） and high protein expression of NLRP3， Caspase-1， IL-1β， and ASC （P<0.05）. Compared with the model group， DHP and MCC950 groups demonstrated low levels of IL-1β， IL-18， and TNF-α （P<0.01） and low protein expression of NLRP3， Caspase-1， IL-1β， and ASC （P<0.01）. Compared with the blank group， the C57BL/6 model group displayed long time to pass the balance wood （P<0.05）， short time spent on the rod in the rotarod test （P<0.05）， high levels of IL-1β， IL-18， and TNF-α （P<0.05） and expression of Iba-1 in the midbrain substantia nigra （P<0.05）， low TH expression （P<0.05）， more positive neurons in the FJB staining （P<0.05）， and high expression of NLRP3， Caspase-1， ASC， and IL-1β proteins （P < 0.05）. Compared with the model group， the mice in the DHP and MCC950 groups had short time to pass the balance beam （P<0.01）， long time spent on the rod （P<0.01）， low levels of IL-1β， IL-18， and TNF-α （P<0.01）， low Iba-1 expression in midbrain substantia nigra （P<0.01）， high TH expression （P<0.01）， and small number of positive neurons in the midbrain substantia nigra （P<0.01）. The expression of NLRP3， ASC， and IL-1β proteins was lower in the MCC950 group （P<0.01）， and the expression of NLRP3， ASC， Caspase-1 and IL-1β proteins was lower in the DHP equivalent-dose group （P<0.01） than in the model group. ConclusionDHP has anti-oxidative stress effect. It regulates the expression of NLRP3 inflammasome and inhibits the overactivation of microglia， thereby alleviating the neuroinflammatory injury in PD and exerting the neuroprotective effect.

Transcriptome of congenital talipes equinovarus based on RNA sequencing / 国际儿科学杂志

Objective:To sequence the whole transcriptomics of congenital talipes equinovarus(CTEV)by RNA sequencing(RNA-Seq)and to compare the differential expression of mRNA, long non-coding RNA(lncRNA), circular RNA(circRNA)and microRNA(miRNA)between CTEV and normal children.Methods:RNA was extracted from plasma samples of 3 CTEV children(experimental group)and 3 normal children(control group). After RNA-Seq, the differentially expressed genes(DEG)and transcripts of CTEV and normal children were screened out.Gene ontology analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were carried out for the DEG.Results:The gene expression profile was successfully constructed.There were 181 DGE in the experimental group and control group, including 58 up-regulated genes and 123 down-regulated genes.A total of 23 lncRNA, 12 up-regulated and 11 down-regulated, were differentially expressed in the present study.There were 23 miRNA differentially expressed, including 11 up-regulated and 12 down-regulated miRNA.No differential expression of circRNA was found in the present study.The expression of secreted phosphoprotein 1(SPP1)and ribosomal protein S27(RPS27)was significantly different in the experimental group and the control group with the fold change being 82.24 and 0.01, respectively.Conclusion:DGE in the plasma samples of CTEV and normal children were analysed by full transcriptome sequencing.SPP1 and RPS27 may be the candidate genes of CTEV.

Development and application of optogenetic tools / 生物工程学报

Dynamic variations of the cell microenvironment can affect cell differentiation, cell signaling pathways, individual growth, and disease. Optogenetics combines gene-encoded protein expression with optical controlling, and offers a novel, reversible, non-invasive and spatiotemporal-specific research tool to dynamically or reversibly regulate cell signaling pathways, subcellular localization and gene expression. This review summarizes the types of optogenetic components and the involved cellular signaling pathways, and explores the application and future prospects of the light-controlled cell signaling pathways.

The molecular regulatory mechanism of co-treatment with LA and PCA on P38 MAPK signaling pathway in the neurons of TX suckling mice / 中国神经精神疾病杂志

Objective To detect the molecular regulatory mechanism of co-treatment with LA and PCA on P38 MAPK signaling Pathway in the Neurons of Wilson's Disease Model-TX mice.Methods The neurons of TX suckling mice were isolated and cultured by primary method,and were divided into control group,model group,ALA group,PCA group and combined group.Flow cytometry was used to analyze the expression of ROS and JC-1.Western blot was used to detect the expression of P38 MAPK,Cyt C,Caspase 9 and Caspase 3.Results Flow cytometry results showed that MFI of ROS was 59.29±1.22,53.19±1.34 and 52.46±1.23 in ALA,PCA and co-treatment.ALA,PCA and co-treatment could significantly reduce the release of ROS and enhance the fluorescence intensity of JC-1 (P＜0.01).Compared with ALA group and PCA group,combined group could reduce the release of ROS and significantly enhance the fluorescence intensity of JC-1.Western blot indicated that the expression levels of P38 MAPK,Cyt C,Caspase 9,Caspase 3 in the neurons of model group had a remarkable increase compared with control group.Compared with the model group,the three treatment groups could decrease the expression levels of P38 MAPK,Cyt C,Caspase 9 and Caspase 3 in the neurons of TX suckling mice (P＜0.01).Meanwhile,the protein levels of P38 MAPK,Cyt C,Caspase 9 and Caspase 3 had a significant decrease compared with ALA group and PCA group.Conclusion he present findings suggest that co-treatment with LA and PCA can increase the copper excretion,reduce copper-induced mitochondria damage and attenuate the neurotoxicity,which in turn decrease neuronal apoptosis and improve neurological impairment of WD.

The molecular regulatory mechanism of co-treatment with LA and PCA on P38 MAPK signaling pathway in the neurons of TX suckling mice / 中国神经精神疾病杂志

Objective To detect the molecular regulatory mechanism of co-treatment with LA and PCA on P38 MAPK signaling Pathway in the Neurons of Wilson's Disease Model-TX mice.Methods The neurons of TX suckling mice were isolated and cultured by primary method,and were divided into control group,model group,ALA group,PCA group and combined group.Flow cytometry was used to analyze the expression of ROS and JC-1.Western blot was used to detect the expression of P38 MAPK,Cyt C,Caspase 9 and Caspase 3.Results Flow cytometry results showed that MFI of ROS was 59.29±1.22,53.19±1.34 and 52.46±1.23 in ALA,PCA and co-treatment.ALA,PCA and co-treatment could significantly reduce the release of ROS and enhance the fluorescence intensity of JC-1 (P＜0.01).Compared with ALA group and PCA group,combined group could reduce the release of ROS and significantly enhance the fluorescence intensity of JC-1.Western blot indicated that the expression levels of P38 MAPK,Cyt C,Caspase 9,Caspase 3 in the neurons of model group had a remarkable increase compared with control group.Compared with the model group,the three treatment groups could decrease the expression levels of P38 MAPK,Cyt C,Caspase 9 and Caspase 3 in the neurons of TX suckling mice (P＜0.01).Meanwhile,the protein levels of P38 MAPK,Cyt C,Caspase 9 and Caspase 3 had a significant decrease compared with ALA group and PCA group.Conclusion he present findings suggest that co-treatment with LA and PCA can increase the copper excretion,reduce copper-induced mitochondria damage and attenuate the neurotoxicity,which in turn decrease neuronal apoptosis and improve neurological impairment of WD.

X-linked dominant protoporphyria:report of a pedigree and detection of ALAS2 gene mutations / 中华皮肤科杂志

Objective To report a pedigree with X?linked dominant protoporphyria(XLDPP), and to detect 5?aminolevulinic acid synthetase 2(ALAS2)gene mutations in this pedigree. Methods A clinical investigation was performed in a pedigree with XLDPP, and relevant data were collected from family members. A next?generation sequencing method was applied to screen possible mutation sites, and Sanger sequencing was performed to determine pathogenic gene mutations. Dermoscopy was conducted to observe skin lesions in the patients with XLDPP, and the Fotofinder system and very high frequency (VHF) ultrasound system were utilized to assess the severity of photodamage. Liver and gallbladder ultrasonography as well as blood examination were performed for all the family members. Results A deletion mutation, c.1706?1709ΔAGTG, was detected in the ALAS2 gene on the X chromosomes of all the patients in this family, which led to replacement or loss of 19-20 C?terminal residues through transcriptional frameshifting, and eventually caused an increase in ALAS2 activity. In the patients with XLDPP, skin photodamage was relatively severe;protoporphyrin?induced hepatobiliary damage was observed and aggravated with age;anemia and iron deficiency occurred sometimes. Conclusion The deletion mutation c.1706?1709ΔAGTG of the ALAS2 gene may be the underlying cause of XLDPP in this pedigree.

Efficacy and safety of topical PUVA treatment for refractory lesions of mycosis fungoides / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of topical PUVA treatment of refractory lesions of mycosis fungoides.</p><p><b>METHODS</b>From January 2008 to 2014, a total of 10 patients (4 males and 6 females) with mycosis fungoides were treated with topical PUVA in Peking Union Medical College Hospital, including 7 cases in plaque stage and 3 cases in tumor stage. The average number of lesions were 1.9±0.9. The median age of these patients was (46.0±9.4) years. The average course of disease was (12.4±7.7) years. Psoralen was applied topically on treatment area 30 min before total body UVA irradiation treatment, 3 times a week. And the efficiency and safety of the therapy were evaluated.</p><p><b>RESULTS</b>All the patients were treated with topical PUVA with a median total dose of (161.60±135.96) J/cm2 in an average of (18.10±14.61) fractions. Total dose of UVA was (1 953.25±829.73) J/cm2, and total number of treatment was (261.90±116.79) fractions. The total treatment time was (45.80±26.64) months. Complete clinical response (CR) rate was 60.0%, partial response (PR) rate was 30.0%, and the overall response rate (CR+PR) was 90.0%. One patient showed no response. No severe acute or chronic side effects were observed.</p><p><b>CONCLUSION</b>Topical PUVA therapy is effective in the treatment of refractory lesions of mycosis fungoides with little severe side effects.</p>

Impact of gestational weight gain and pre-pregnant body mass index on pregnant outcomes / 中华围产医学杂志

Objective To evaluate the effects of gestational weight gain(GWG) in different prepregnant body mass index (BMI) women on perinatal outcomes and to provide evidences for gestational weight management protocol.Methods Totally,2409 healthy singleton pregnant women accepted regular prenatal examinations in Nanjing Drum Tower Hospital from January 2009 to April 2010 were recruited in this study.They were divided into three groups according to pre-pregnant BMI,which were low BMI group (BMI＜18.5),normal BMI group (BMI 18.5-) and high BMI group (BMI≥24.0).According to GWG,the difference between pre-delivery maximal weight and prepregnant weight,the low and normal BMI women were divided into ＜10 kg,10 kg-and ≥15 kg GWG subgroups,and the high BMI women were divided into ＜5 kg,5 kg-,10 kg and ≥15 kg GWG subgroups.Data including gestational age,delivery modc,newborns' birth weight,Apgar score and incidences of gestational complications,such as hypertensive disorders complicating pregnancy (HDP),gestational diabetes mellitus (GDM),macrosomia,fetal growth restriction (FGR) and preterm birth,were recorded.Analysis of variance,Student-Newman Keuls,Chi-square test and Fisher exact test were applied for statistics.Results (1) Among the 2409 women,the percentages of low,normal and high BMI groups were 18.5％ (n=445),69.9％ (n=1685) and 11.6％ (n=279),respectively.The incidences of HDP,GDM,macrosomia and caesarean delivery in high BMI group were 12.9％ (n=36),17.9％ (n=50),13.6％ (n=38) and 52.3％ (n=146),respectively,higher than those in low BMI group [3.4％ (n=15),4.3 ％ (n=19),3.8％ (n=17) and 25.8％(n=115),x2 =23.8,37.1,23.5 and 50.2,P＜0.05] and those in normal BMI group [5.5％ (n=92),7.8％ (n=132),7.8％ (n=132)and 31.6％ (n=532),x2=21.8,29.0,10.1 and 3.4,P＜0.05].(2) In normal BMI group,the rates of FGR and preterm birth in GWG ＜10 kg subgroup were 3.5％ (4/115) and 8.7％ (10/115),higher than those in GWG 10 kg-subgroup [0.7％(4/548) and 3.3％(18/548),x2=6.0 and 6.9,P＜0.05] and GWG ≥15 kg subgroup [(0.8 ％ (8/1022) and 3.6％ (37/1022),x2=7.2 and 6.7,P＜0.05].The rates of macrosomia and cesarean delivery in GWG ≥15 kg subgroup were 10.7％ (109/1022) and 34.5％ (353/1022),higher than those in GWG＜10 kgsubgroup [3.5％ (4/115) and 32.2％ (37/115),x2=6.0 and 63.0,P＜0.05] and GWG 10 kg subgroup [3.5％ (19/548) and 25.9％ (142/548),x2=24.7 and 31.0,P＜0.05].(3) In high BMI group,the incidences of all pregnancy complications and perinatal outcomes did not show statistical significance among the four GWG subgroups (P＞0.05).Conclusions High prepregnant BMI is a high risk factor of pregnancy complications.It is suggested that normal BMI women should control GWG at 10-15 kg to lower the incidences of pregnancy complications.