Si-Wu-Tang attenuates liver fibrosis via regulating lncRNA H19-dependent pathways involving cytoskeleton remodeling and ECM deposition / 中国天然药物

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo. In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.

Chuanxiong Rhizoma extracts prevent liver fibrosis via targeting CTCF-c-MYC-H19 pathway / 中草药·英文版

OBJECTIVE@#Hepatic fibrosis has been widely considered as a conjoint consequence of almost all chronic liver diseases. Chuanxiong Rhizoma (Chuanxiong in Chinese, CX) is a traditional Chinese herbal product to prevent cerebrovascular, gynecologic and hepatic diseases. Our previous study found that CX extracts significantly reduced collagen contraction force of hepatic stellate cells (HSCs). Here, this study aimed to compare the protection of different CX extracts on bile duct ligation (BDL)-induced liver fibrosis and investigate plausible underlying mechanisms.@*METHODS@#The active compounds of CX extracts were identified by high performance liquid chromatography (HPLC). Network pharmacology was used to determine potential targets of CX against hepatic fibrosis. Bile duct hyperplasia and liver fibrosis were evaluated by serologic testing and histopathological evaluation. The expression of targets of interest was determined by quantitative real-time PCR (qPCR) and Western blot.@*RESULTS@#Different CX extracts were identified by tetramethylpyrazine, ferulic acid and senkyunolide A. Based on the network pharmacological analysis, 42 overlap targets were obtained via merging the candidates targets of CX and liver fibrosis. Different aqueous, alkaloid and phthalide extracts of CX (CXAE, CXAL and CXPHL) significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor (CTCF)-c-MYC-long non-coding RNA H19 (H19) pathway in the BDL-induced mouse model. Meanwhile, CX extracts, especially CXAL and CXPHL also suppressed CTCF-c-MYC-H19 pathway and inhibited ductular reaction in cholangiocytes stimulated with taurocholate acid (TCA), lithocholic acid (LCA) and transforming growth factor beta (TGF-β), as illustrated by decreased bile duct proliferation markers.@*CONCLUSION@#Our data supported that different CX extracts, especially CXAL and CXPHL significantly alleviated hepatic fibrosis and bile duct hyperplasia via inhibiting CTCF-c-MYC-H19 pathway, providing novel insights into the anti-fibrotic mechanism of CX.

Analysis of TUBB4A gene variant in a patient with adolescent-onset hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a patient with adolescent-onset hypomyelinated leukodystrophy with atrophy of basal ganglia and cerebellum (H-ABC).@*METHODS@#A patient who was diagnosed with H-ABC in March 2018 at the First Affiliated Hospital of Nanjing Medical University was selected as the study subject. Clinical data was collected. Peripheral venous blood samples of the patient and his parents were collected. The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.@*RESULTS@#The patient, a 31-year-old male, had manifested with developmental retardation, cognitive decline and abnormal gait. WES revealed that he has harbored a heterozygous c.286G>A variant of the TUBB4A gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Analysis with SIFT online software indicated the amino acid encoded by this variant is highly conserved among various species. This variant has been recorded by the Human Gene Mutation Database (HGMD) with a low population frequency. The 3D structure constructed by PyMOL software showed that the variant has a harmful effect on the structure and function of the protein. According to the guidelines formulated by the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic.@*CONCLUSION@#The c.286G>A (p.Gly96Arg) variant of the TUBB4A gene probably underlay the hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum in this patient. Above finding has enriched the spectrum of TUBB4A gene variants and enabled early definitive diagnosis of this disorder.

Protein Containing the GGDEF Domain Affects Motility and Biofilm Formation in Vibrio cholerae and is Negatively Regulated by Fur and HapR / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate whether the VCA0560 gene acts as an active diguanylate cyclase (DGC) in Vibrio cholerae and how its transcription is regulated by Fur and HapR.@*METHODS@#The roles of VCA0560 was investigated by utilizing various phenotypic assays, including colony morphological characterization, crystal violet staining, Cyclic di-GMP (c-di-GMP) quantification, and swimming motility assay. The regulation of the VCA0560 gene by Fur and HapR was analyzed by luminescence assay, electrophoretic mobility shift assay, and DNase I footprinting.@*RESULTS@#VCA0560 gene mutation did not affect biofilm formation, motility, and c-di-GMP synthesis in V. cholerae, and its overexpression remarkably enhanced biofilm formation and intracellular c-di-GMP level but reduced motility capacity. The transcription of the VCA0560 gene was directly repressed by Fur and the master quorum sensing regulator HapR.@*CONCLUSION@#Overexpressed VCA0560 functions as an active DGC in V. cholerae, and its transcription is repressed by Fur and HapR.

Research on cellular damages and astrocyte activation after cerebral ischemia and reperfusion / 中国药理学通报

Aim To observe cellular damage and astrocyte activation at different time points of cerebral ischemia and reperfusion. Methods The middle cerebral artery of male SpragueDawley rats was occluded for 90 min followed by different time points of reperfusion. Eighty-five SPF male SD rats were randomly divided into control group (Sham), IR3, 6, 12, 24 and IR48h (MCAO followed by 48 h of reperfusion) group. Cerebral ischemia and reperfusion injury was observed by HE staining, and the structure of astrocytes was estimated with transmission electron microscopy (TEM). GFAP expression was detected by immunofluorescence staining and Western blot. Results Cerebral ischemia following by different time points of reperfusion led to different degrees of cellular damage, which was the most serious at 24 h of reperfusion. TEM showed destruction of astrocytes structure, swollen organelles and broken mitochondrial ridge. After cerebral ischemia-reperfusion, the expression levels of GFAP were significant up-regulated in the ischemic penumbra cortex and the highest was at 48 h of reperfusion, indicating astrocytes were activated. In addition, the results showed the gradual decrease in GFAP expression in the infarct core. Conclusions After cerebral ischemia-reperfusion, cellular damage is aggravated, and astrocytes are gradually activated in the ischemic penumbra. With the extension of reperfusion time, the boundaries of infarct area and ischemic area are gradually clear, and scarring may occur.

Chuanxiong Rhizoma extracts prevent cholestatic liver injury by targeting H3K9ac-mediated and cholangiocyte-derived secretory protein PAI-1 and FN / 中国天然药物

Chuanxiong Rhizoma (CX, the dried rhizome of Ligusticum wallichii Franch.), a well-known traditional Chinese medicine, is clinically used for treating cardiovascular, cerebrovascular and hepatobiliary diseases. Cholestatic liver damage is one of the chronic liver diseases with limited effective therapeutic strategies. Currently, little is known about the mechanism links between CX-induced anti-cholestatic action and intercellular communication between cholangiocytes and hepatic stellate cells (HSCs). The study aimed to evaluate the hepatoprotective activity of different CX extracts including the aqueous, alkaloid, phenolic acid and phthalide extracts of CX (CXAE, CXAL, CXPA and CXPHL) and investigate the intercellular communication-related mechanisms by which the most effective extracts work on cholestatic liver injury. The active compounds of different CX extracts were identified by UPLC-MS/MS. A cholestatic liver injury mouse model induced by bile duct ligation (BDL), and transforming growth factor-β (TGF-β)-treated human intrahepatic biliary epithelial cholangiocytes (HIBECs) and HSC cell line (LX-2 cells) were used for in vivo and in vitro studies. Histological and other biological techniques were also applied. The results indicated that CXAE, CXAL and CXPHL significantly reduced ductular reaction (DR) and improved liver fibrosis in the BDL mice. Meanwhile, both CXAE and CXPHL suppressed DR in injured HIBECs and reduced collagen contraction force and the expression of fibrosis biomarkers in LX-2 cells treated with TGF-β. CXPHL suppressed the transcription and transfer of plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) from the 'DR-like' cholangiocytes to activated HSCs. Mechanistically, the inhibition of PAI-1 and FN by CXPHL was attributed to the untight combination of the acetyltransferase KAT2A and SMAD3, followdd by the suppression of histone 3 lysine 9 acetylation (H3K9ac)-mediated transcription in cholangiocytes. In conclusion, CXPHL exerts stronger anti-cholestatic activity in vivo and in vitro than other CX extracts, and its protective effect on the intracellular communication between cholangiocytes and HSCs is achieved by reducing KAT2A/H3K9ac-mediated transcription and release of PAI-1 and FN.

Cost-effectiveness analysis of Chaiyin Granules in treatment of influenza / 中国中药杂志

This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.

Research progress in gene therapy for amyotrophic lateral sclerosis / 中华神经科杂志

Amyotrophic lateral sclerosis is a neurodegenerative disease caused by the loss of motor neurons in the brain and spinal cord. There is currently no effective cure. The emergence of gene therapy brings hope to treatment, which can be achieved by delivering transgenes to replace or correct defective genes, as well as the expression of neurotrophic factors. The vectors of gene therapy can be viral vectors and non-viral vectors. Lentiviral vectors can be used to deliver therapeutic sequences to motor neurons in the central nervous system. Adeno-associated viruses can effectively mediate gene expression and delivery of neurotrophic factors. Gene editing and antisense oligonucleotides therapy are also perspective treatment options. This article summarizes gene therapy for amyotrophic lateral sclerosis from basic experiments and clinical trials.

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

Parkinson's disease （PD） is a neurodegenerative disease that seriously endangers the health of the middle-aged and elderly people. The main clinical manifestations include motor symptoms such as bradykinesia， static tremor， and myotonia and non-motor symptoms like constipation， mental disorders， sleep disorders， and autonomic nervous dysfunction. Its etiology and pathogenesis have not been fully understood， and the clinical efficacy is not satisfactory. By searching the relevant literature in China and abroad in recent years， this paper summarized the etiology， pathogenesis， and treatment of PD in both traditional Chinese medicine （TCM） and western medicine as well as the integrated TCM and Western medicine treatment. In general， liver and kidney deficiency is recognized by domestic experts in related fields as the main pathogenesis of PD. The abnormal aggregation of α-synuclein， oxidative stress， mitochondrial dysfunction， ubiquitin-proteasome system dysfunction， neuroinflammation， autophagy， microbiota-gut-brain axis regulation， and excitatory neurotoxicity are closely related to the pathogenesis of this disease. At present， treatment based on syndrome differentiation， empirical formulae from famous doctors， single Chinese herbs， and acupuncture and moxibustion are mainly adopted for the tackling of PD in TCM. Western medicine is still dominated by drug replacement therapy， supplemented by such surgical treatments as traditional immunotherapy， neurotrophic factors， and deep brain stimulation （DBS）， rehabilitation and exercise therapy， and scientific nursing. Gene therapy has become a new technical means for the treatment of this disease in recent years. In addition， the combined therapy of TCM and Western medicine has received increasing importance. This paper reviewed the pathogenesis and treatment of PD in TCM and Western medicine， so as to provide reference for its clinical diagnosis and treatment.

Health-seeking delay in tuberculosis among students inYining City from 2009 to 2020 / 预防医学

Objective@# To investigate the health-seeking delay in tuberculosis among school students in Yining City, Xinjiang Uygur Autonomous Region from 2009 to 2020, and analyze the influencing factors, so as to provide the evidence for reducing the health-seeking delay in tuberculosis among students in Yining City.@*Methods@#The demographic features and diagnosis of students with tuberculosis in Yining City from 2009 to 2020 were retrieved from the Tuberculosis Management Information System of the Chinese Disease Control and Prevention Information System, and the factors affecting the health-seeking delay in tuberculosis were identified using the multivariable logistic regression analysis.@*Results@#A total of 443 students with tuberculosis were reported in Yining City from 2009 to 2020, including 209 boys and 234 girls, with a male/female ratio of 1∶1.12. There were 29 primary school students ( 6.55% ), 81 junior high school students ( 18.28% ), 187 high school students ( 42.21% ) and 146 college students ( 32.96% ) reporting tuberculosis, and 394 cases ( 88.94% ) had locally registered residence. There were 287 students with health-seeking delay in tuberculosis ( 64.79% ), and the median duration of health-seeking delay was 35 ( interquartile range, 33 ) days. Multivariable logistic regression analysis showed that registered residence ( local, OR=1.899, 95%CI: 1.004-3.591 ) and origin of tuberculosis patients ( clinical consultation, OR=3.448, 95%CI: 1.755-6.775; recommendation for symptoms, OR=3.215, 95%CI: 1.161-8.900; tracking, OR=2.415, 95%CI: 1.269-4.596 ) and diagnostic results ( positive sputum smears, OR=3.081, 95%CI: 1.710-5.551 ) statistically correlated with health-seeking delay among students with tuberculosis.@*Conclusions@#The proportion of health-seeking delay in tuberculosis was high among students in Yining City from 2009 to 2020; registered residence, origin of tuberculosis patients and diagnostic results were associated.

Influencing factors of tuberculosis in the elderly in Urumqi / 公共卫生与预防医学

Objective To identify factors that affect the occurrence of tuberculosis (TB) in the elderly over 60 years old in Urumqi, and to provide a basis for the prevention and treatment of tuberculosis in the elderly. Methods A 1:2 matched case-control study was conducted using a self-designed questionnaire from April 2016 to April 2017 in Urumqi, China. A conditional logistic regression analysis was carried out to identify the influencing factors for the occurrence of TB in the elderly. Results A total of 575 valid questionnaires were collected in the present study, and the age range was 60-89 years old. There were 302 males, accounting for 52.5% of the total. Multivariate logistic regression model analysis showed that an increase of one person per 100 square meters in a home elevated the risk of the development of TB by 67% (odds ratio (OR) 1.67; 95% confidence interval (CI) 1.36-2.06; P<0.001). Family income level was also important, and the risk of TB development was 4.72 times higher in families with less than 5,000 CNY a month than those with monthly incomes over 10 000 CNY (OR 4.72; 95%CI 2.29-9.75; P<0.001). The risk was significantly higher among people going out more than 3 to 7 days a week compared to those going out 0 to 2 days a week (OR 4.53; 95%CI 2.72-7.53; P<0.001). Compared with people who were not in contact with TB patients, the risk increased among those who had TB contacts (OR 3.72; 95%CI 1.45-9.70; P=0.006). In addition, the risk of TB onset in hypertension patients was significantly decreased (OR 0.57; 95%CI 0.35-0.91; P=0.018). Conclusion In the present study five factors are found to be associated with the occurrence of TB among the elderly in Urumqi, China. The future TB control program should pay special attention to the elderly population with the above risk factors.

A new classification of maxillary defect and simultaneous accurate reconstruction / 中华耳鼻咽喉头颈外科杂志

Objective: To select the preferred flaps for the reconstruction of different maxillary defects and to propose a new classification of maxillary defects. Methods: A total of 219 patients (136 males and 83 females) underwent the simultaneous reconstruction of maxillary defects in the Beijing Tongren Hospital, Capital Medical University, between January 2005 and December 2018 were reviewed. Age ranged from 16 to 78 years. Based on the proposed new classification of the maxillary defects, 22 patients with class Ⅰ defects (inferior maxillectomy), 44 patients with class Ⅱ defects (supperior maxillectomy), 132 patients with class Ⅲ defects (total maxillectomy) and 21 patients with class Ⅳ defects (extensive maxillectomy) were enrolled. Survival rate, functional and aesthetic outcomes of flaps were evaluated. Survival analysis was performed in 169 patients with malignant tumor, Kaplan-Meier method was used to calculate the survival rate, and Log-rank method was used to compare the difference of survival rate in each group. Results: A total of 234 repairs for maxillary defects were performed in 219 patients. Fibula flaps were used in 4/13 of class Ⅰ defects; temporal muscle flaps (11/24, 45.8%) and anterolateral thigh flaps (6/24, 25.0%) used in class Ⅱ defects; temporal muscle flaps (71/128, 55.5%), anterolateral thigh flaps (6/24, 25.0%) and fibula flaps (12/128, 9.4%) used in class Ⅲ defects; and anterolateral thigh flaps (8/20, 40.0%) and rectus abdominis flaps (8/20, 40.0%) used in class Ⅳ defects. The success rate of local pedicled flaps was 95.6% (109/114) and that of free flaps was 95.8% (115/120). Thrombosis(10/234,4.3%) was a main reason for repair failure. Among the followed-up 88 patients, swallowing and speech functions recovered, 82 (93.2%) of them were satisfied with appearance, and 75 (85.2%) were satisfied with visual field. The 3-year and 5-year overall survival rates were 66.5% and 63.6%, and the 3-year and 5-year disease-free survival rates were 57.1% and 46.2%, respectively, in the 169 patients with malignant tumors. Conclusion: A new classification of maxillary defects is proposed, on which suitable flaps are selected to offer patients good functional and aesthetic outcomes and high quality of life.

Efficacy observation of auricular point sticking in combination with a healthy diet for simple obesity in children / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of combining auricular point sticking and a healthy diet to treat simple obesity in children aged 6-9 years old.Methods: A total of 190 eligible obese kids were divided into an observation group and a control group using the random number table method, with 95 cases in each group. The observation group was intervened by auricular point sticking plus guide on a healthy diet, while the control group was only provided with the guide on a healthy diet. The therapeutic efficacy was observed after intervention for three consecutive months, as well as the changes in body mass (BM), body mass index (BMI), waist circumference (WC), hip circumference (HC), and subcutaneous fat thickness. Results: After the 3-month intervention, the total effective rate was 91.6％ in the observation group, versus 74.7％ in the control group, and the between-group difference was statistically significant (P<0.01); in both groups, the BM, BMI, WC, HC, and subcutaneous fat thickness all decreased significantly (P<0.05), and were lower in the observation group than in the control group, showing statistical significance (P<0.05). Conclusion: Auricular point sticking plus a healthy diet is safe and effective in treating simple obesity in children, producing more significant efficacy than healthy diet intervention alone.

Pathogenic mechanisms of congenital abnormalities of kidney and urinary tract / 中华围产医学杂志

Congenital abnormalities of the kidney and urinary tract (CAKUT) are common congenital malformations identified by prenatal ultrasound. This review summarizes the fetal renal development, the mechanism of CAKUT, and the influence of the fetal environment on CAKUT. CAKUT can manifest as different degrees of renal disease, from transient hydronephrosis to severe bilateral renal dysplasia, a major risk factor for chronic and end-stage renal disease in childhood. Genetic factors and abnormal fetal environment can both contribute to CAKUT. Ultrasound screening is conducive to detect CAKUT but may miss some defects. Monogenic mutations identified in CAKUT can help us gain more insight into the molecular mechanisms of renal development.

Mechanism of Kaixinsan on Learning and Memory Ability and Synaptic Function of APP/PS1 Mice / 中国实验方剂学杂志

Objective:To explore the underlying protective mechanism of Kaixinsan on learning， memory， and synaptic function in APP/PS1 mice. Method:Sixty APP/PS1 mice were randomly divided into a model group， a donepezil （2 mg·kg^-1·d^-1） group， and low- （0.7 g·kg^-1·d^-1）， medium- （1.4 g·kg^-1·d^-1）， and high-dose （2.8 g·kg^-1·d^-1） Kaixinsan groups， and the wild-type mice of the same age in the same litter were assigned to the normal group， with 12 mice in each group. After continuous intragastric administration for two months， the Morris water maze experiment was performed. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The colorimetric assay was used to detect serum content of acetylcholine （ACh）， choline acetyltransferase （ChAT）， acetylcholinesterase （AChE）， and levels of hippocampal reactive oxygen species （ROS）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Real-time fluorescence-based quantitative polymerase chain reaction （Real- time PCR） was used to detect the mRNA expression of hippocampal brain-derived neurotrophic factor （BDNF）， beta-nerve growth factor （NGFB）， discs large homolog (DLG)2， DLG4， and synaptophysin （SYP）. Result:Compared with the normal group， the model group showed prolonged escape latency， reduced number of crossing platforms， shortened stay in the target quadrant （<italic>P</italic><0.01）， decreased number of mitochondria with different shapes and irregular arrangement， some swollen and deformed mitochondria with broken mitochondrial cristae， endolysis， and cytoplasm vacuole， and more cell debris. Additionally， the model group also displayed reduced serum levels of ACh and ChAT， increased AChE （<italic>P</italic><0.01）， elevated hippocampal ROS and MDA （<italic>P</italic><0.05，<italic>P</italic><0.01）， declining SOD and GSH-Px （<italic>P</italic><0.01）， and diminished hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group， the donepezil group， and the medium- and high-dose Kaixinsan groups showed shortened escape latency， increased number of crossing platforms， prolonged stay in the target quadrant （<italic>P</italic><0.05，<italic>P</italic><0.01）， improved mitochondrial damage with a regular shape （mainly oval shape）， relieved mitochondrial swelling and deformation， and clear mitochondrial cristae. Furthermore， the donepezil group， and the medium- and high-dose Kaixinsan groups also exhibited increased serum ACh and ChAT levels （<italic>P</italic><0.05，<italic>P</italic><0.01）， blunted AChE activity （<italic>P</italic><0.05）， reduced hippocampal ROS level （<italic>P</italic><0.05，<italic>P</italic><0.01）， declining MDA level （<italic>P</italic><0.05）， potentiated SOD and GSH-Px activities， and up-regulated hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （<italic>P</italic><0.05，<italic>P</italic><0.01）. In the low-dose Kaixinsan group， the stay time in the target quadrant was prolonged and the expression of hippocampal SYP mRNA was elevated significantly （<italic>P</italic><0.05）. There was no statistical difference in swimming speed between the groups. Conclusion:Kaixinsan can improve the learning and memory ability of APP/PS1 mice by increasing the expression of synaptic plasticity-related proteins， reducing the ultrastructural damage to hippocampal neurons， resisting oxidative stress， and regulating cholinergic neurotransmitters， thereby exerting neuroprotective effects.

Effect of Bushen Tongluo Prescription on Synaptic Plasticity of Hippocampal Neurons of Vascular Dementia Model Rats Based on PI3K/Akt/mTOR Pathway / 中国实验方剂学杂志

Objective:To explore the effect of Bushen Tongluo prescription （BSTLP） on the synaptic plasticity of hippocampal neurons in vascular dementia （VD） model rats and its mechanism. Method:SD male rats of SPF grade were selected. The rat model of VD was established by permanent bilateral ligation of the common carotid artery several times. The model rats were randomly divided into a model group， an insulin-like growth factor-1 （IGF-1， 20 μg·kg^-1） group， high-dose （3 g·kg^-1）， medium-dose （1.5 g·kg^-1）， and low-dose （0.75 g·kg^-1） BSTLP groups. A sham operation group was also set. Drugs were administered to rats by gavage once a day for four weeks. The model group and the sham operation group received the same volume of normal saline. After the last administration， all the rats were detected for spatial learning and memory by the Morris water maze. The apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase （TdT） dUTP nick-end labeling （TUNEL） assay. The changes in synaptic morphological structure and the number of dendritic spines in hippocampal neurons were detected by Golgi's method. The expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， synaptophysin （SYP）， and amyloid precursor protein （APP） in hippocampal neurons were detected by Western blot. Result:Compared with the sham operation group， the model group showed prolonged escape latency， lengthened swimming distance， dwindled the number of times for the platform crossing after platform removal （<italic>P</italic><0.05）， increased apoptotic cells （<italic>P</italic><0.05）， declining synaptic dendritic spines （<italic>P</italic><0.05）， down-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and up-regulated expression level of APP protein in hippocampal neurons （<italic>P</italic><0.05）. Compared with the model group， the BSTLP groups and the IGF-1 group showed shortened escape latency and swimming distance， increased number of times for the platform crossing after platform removal （<italic>P</italic><0.05），declining apoptotic cells （<italic>P</italic><0.05）， up-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and down-regulated expression level of APP protein in hippocampal neurons （<italic>P</italic><0.05）. Compared with the IGF-1 group， the high-dose BSTLP group showed no significant difference in the escape latency， swimming distance， the number of times for the platform crossing after platform removal， apoptotic cells， synaptic dendritic spines， and expression levels of PI3K， Akt， mTOR， SYP， and APP proteins in hippocampal neurons. However， the differences were significant in the medium-dose and low-dose BSTLP groups （<italic>P</italic><0.05）. Conclusion:BSTLP can improve the learning and memory of rats with VD. The mechanism is presumedly related to the activation of thePI3K/Akt/mTOR pathway and improvement of synaptic plasticity of hippocampal neurons.

Retrospective study of thyroid invasion and central lymph node metastasis in 124 patients with hypopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the characteristics of thyroid invasion and central lymph node metastasis of hypopharyngeal carcinoma, and the impact on survival rate and quality of life. Methods: A retrospective analysis of 124 cases (122 males and 2 females with age range from 36 to 78 years old) with laryngopharyngeal squamous cell carcinoma who were initially treated in the Department of Head and Neck Surgery, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2014 to December 2017 was performed. The clinical data included tumor location, pathological T stage, pathological N stage, invasion of thyroid gland, central lymph node metastasis, surgical procedures and so on. Patients were grouped according to if presence of thyroid invasion and central lymph node metastasis. With follow-up, the survival was analyzed by Kaplan-Meier method, and tumor recurrence and metastasis were evaluated. Results: Of the patients, 12 patients had thyroid involvement and 5 patients had central lymph node metastasis. The incidence of thyroid involvement was 8.16% (8/98) in pyriform sinus, 1/18 in posterior pharyngeal wall and 3/8 in posterior cricoid wall, with statistically significant difference (χ2=15.076,P=0.008). The incidence of central lymph node metastasis was 1.02% (1/98) in pyriform sinus, 3/18 in posterior pharyngeal wall and 1/8 in posterior cricoid wall, also with statistically significant difference (χ2=11.205, P=0.008). There was no statistical correlation between thyroid invasion or central lymph node metastasis and gender, smoking or alcohol exposure history and tumor pathological differentiation (all P>0.05). The 3-year overall survival rate was 80.65% and the 3-year recurrence free rate was 85.48%. Totally 24 patients died in 3 years, including 4 cases in thyroid invasion group and 1 case in central lymph node metastasis group. Local recurrence occurred in 18 patients, including 4 cases in thyroid invasion group and 1 case in central lymph node metastasis group. There was no significant difference in survival between patients with and without thyroid invasion and central lymph node metastasis (all P>0.05). There were significantly difference in 3-year overall survival and relapse-free survival among the groups with different T stages, N stages, pathological stages and tumor pathological differentiation levels (all P<0.05). There were significantly differences in the levels of serum calcium and FT3 between the groups with or without thyroid invasion and central lymph node metastasis (all P<0.05). Conclusion: The incidences of thyroid invasion and central lymph node metastasis of hypopharyngeal carcinoma are rare, and the risk of occurrence is related to the primary site of tumor. Comprehensive evaluation, correct decision-making and accurate treatment could be helpful to cure radically the tumor, to prevent recurrence and to improve the quality of life of patients.

Protection of total Flavonoids from Anchusa italica Retz, and four compounds on hypoxia-reoxygenation induced injury in myocardial cells and its mechanism / 中国药理学通报

Aim To observe the protective effects of total flavonoids from Anchusa italica Retz, and four compounds on hypoxia/reoxygenation (H / R) injury in myocardial cells and to explore the mechanisms. Methods Primary neonatal rat cardiomyocytes were isolated, cultured and were randomly divided into different groups. The H / R model of cultured neonatal rat cardiomyocytes was developed. The related indexes were determined after administration. Results Compared with model group, the total flavonoids and the four compounds could increase the survival rate of H / R cardiomyocytes (P < 0. 01), reduce the leakage of LDH (P < 0 . 0 1), reduce the content of M DA (P < 0 . 0 1), significantly increase the activity of SOD (P <0. 01), significantly decrease the early apoptosis index and increase the mitochondrial membrane potential (P < 0. 01) . The activation of key proteins in NF-KB signaling pathway was inhibited, the proportion of Bax / Bc l - 2, beclin-1 and p62 significantly decreased (P < 0. 01), and the expression of apoptosis related proteins NLRP3, IL - lß and GSDMD significantly decreased (P <0. 0 1) . Conclusions The total flavonoids and four compounds can alleviate the damage of H/R on cardiomyocytes. The mechanism is related to the inhibition of the activation of NF-KB signaling pathway and the excessive autophagy of cardiomyocytes, alleviation of the scorch death of cardiomyocytes, and reduction of the apoptosis of cardiomyocytes.

Association between healthy lifestyle and risk of rehospitalization in male or female patients with chronic heart failure / 中华心血管病杂志

Objective: To explore the association between healthy lifestyle and risk of rehospitalization in male or female patients with chronic heart failure (CHF). Methods: Discharged patients with CHF of Henan Provincial People's Hospital Collaboration Hospital were recruited in our study from January 1,2017 to December 31, 2018. The basic information of patients were collected through the electronic medical record system,the questionnaires were used to collect the related influencing factors. Healthy lifestyle includes 4 items, namely non-smoking, moderate exercise, healthy body mass index (BMI) and reasonable diet.Multivariate logistic regression was used to analyze the association between healthy lifestyle and the risk of rehospitalization of CHF patients of different genders. Results: A total of 2 697 patients with CHF were enrolled in this study, including 1 308 male patients(621 rehospitalizations,687 controls)and 1 389 female patients(684 rehospitalizations,705 controls).Among male patients, there was no significant difference in age, residence, marital status, education level, average monthly income, and medical insurance between the rehospitalization group and the control group (all P>0.05). Among female patients, there was no significant difference in age, residence, marital status, education level, average monthly income, and medical insurance between the rehospitalization group and the control group (all P>0.05). Whether in male or female patients with CHF, we found that patients with 4 healthy lifestyles were associated with reduced risk of rehospitalization: male patients OR=0.34, 95%CI 0.11-0.99, P=0.002,female patients OR=0.27, 95%CI 0.13-0.79, P=0.012. A combination of non-smoking and any other 2 healthy lifestyles was associated with reduced risk of rehospitalization: male patients with no smoking, moderate exercise, healthy BMI, OR=0.32, 95%CI 0.11-0.99, P=0.043; female patients OR=0.28, 95%CI 0.12-0.93, P=0.032;male patients with no smoking, moderate exercise, reasonable diet OR=0.42, 95%CI 0.24-0.98, P=0.044,female patients OR=0.40, 95%CI 0.12-0.94, P=0.031;male patients with no smoking, healthy BMI, reasonable diet OR=0.31, 95%CI 0.21-0.92, P=0.039,female patients OR=0.27,95%CI 0.11-0.87, P=0.014. In female patients with CHF, the combination of non-smoking and moderate sports was associated with reduced risk of hospitalization (OR=0.23, 95%CI 0.19-0.97, P=0.038), while no similar results were seen in male patients (OR=0.65, 95%CI 0.33-1.84, P=0.315). Conclusion: Healthy lifestyle is associated with reduced risk of rehospitalization in patients with CHF, and the related healthy lifestyle and its combination may differ between male and female patients.

Exploration of active components and mechanism of Scutellariae Radix-Phellodendri Chinensis Cortex drug pair in treatment of psoriasis based on network pharmacology and molecular docking / 中国中药杂志

This paper aims to explore active components and mechanism of Scutellariae Radix(SR)-Phellodendri Chinensis Cortex(PCC) drug pair in treatment of psoriasis by network pharmacology and molecular docking. Specifically, the chemical components of SR and PCC were retrieved from literature and TCMSP, as well as targets of these components from PharmMapper and UniProt, and the targets related to psoriasis from OMIM, TTD, PharmGkb, and DrugBank. Then the chemical component-medicinal target, protein-protein interaction(PPI), and chemical component-psoriasis target networks were constructed by Cytoscape. Gene ontology(GO) term enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed based on Metascape. Finally, molecular docking of the chemical components(high degree) with core therapeutic targets was carried out by AutoDock vina. The results showed 88 compounds of SR and PCC(including baicalin, wogonoside, berberine and phellodendrine) and 30 targets of the pair in the treatment of psoriasis. The 30 targets mainly involved the biological processes such as neutrophil mediated immunity(GO: 0002446) and T cell activation(GO: 0042110), and the signaling pathways such as metabolism of xenobiotics by cytochrome P450(hsa00980), apoptosis(hsa04210), and PI3 K-Akt signaling pathway(hsa04151). The results of molecular docking demonstrated that the main active components can spontaneously bind to the targets and the binding energy of 46 components with epidermal growth factor receptor(EGFR) was less than-8 kcal·mol~(-1). According to the PPI analysis, EGFR may be a key target for the treatment of psoriasis. Active components such as baicalin and berberine had high binding affinity with EGFR. This study preliminarily revealed the multi-component, multi-target and multi-pathway mechanism of SR-PCC drug pair in the treatment of psoriasis, which provided theoretical basis for the research on the mechanism of the drug pair in the treatment of psoriasis.