Epilepsy is a chronic neurological disorder with different etiologies. Despite of many antiepileptic drugs (AEDs) used in clinical treatment, about 30% of the patients have uncontrolled onset, and combined use of different AEDs or new AEDs are needed. The new AEDs should have satisfactory clinical efficacy, tolerability and pharmacokinetic properties, and minimal adverse effects. By now there have been about 20 novel AEDs; most of them are derivatives or analogues of current AEDs. Brivaracetam (BRI) is the derivative of levetiracetam (LEV). This review summarizes the mechanisms of action, pharmacokinetic profiles, tolerability, pharmacology and toxicology, and side effects of LEV and its derivative BRI.

Objective To investigate the effects of connective tissue growth factor (CTGF) siRNA delivered by pRetro-Super (PRS) retrovirus vector on extracellular matrix and VEGF expression in human peritoneal mesothelial cells (HPMC). Methods Four pairs of oligonucleotides including 64 bp DNA were designed and synthesized in vitro according to siRNA target sequence and PRS retrovirus desire.PRS-CTGF-siRNA1-4 recombinant retrovirus vectors were constructed.The recombinant retrovirus vectors containing CTGF-siRNA were transferred into PT67 packaging cell lines with lipefectamine 2000,then infected HPMC.mRNA expression was determined by semi-quantitative RT-PCR and protein expression was determined by Western blot.Results Both mRNA and protein expressions of CTGF,FN,Col I,laminin (LN) and VEGF were significantly increased in HPMC with 5 μg/L TGF-β1 stimulation (P＜0.01,respectively).CTGF,FN,Col I,LN mRNA and protein and VEGF mRNA expression stimulated by TGF-β1 were significantly decreased in HPMC infected with PRS-CTGF-siRNA1～4 retrovirus vectors (P＜0.01,respectively).The inhibitory rates on CTGF were 69.3%,22.2%,27.4% and 38.8%,respectively (P＜0.01).At the same time,there was also a significant reduction of VEGF protein expression in HPMC infected with PRS-CTGF-siRNA1 vector (P＜0.01).There was no significant difference in HPMC infected with PRS void vector. Conclusion CTGF siRNA delivered by PRS retrovirus vector can effectively inhibit the enhancement of extracellular matrix and VEGF expression stimulated by TGF-β1 in HPMC.

Objective To investigate the role of oxidative stress in the epithelial-to-mesenchymal transdifferentiation (EMT) of peritoneal mesothelial cells in rat model of peritoneal fibrosis and the effect of probucol on peritoneal fibrosis. Methods The rat model of peritoneal fibrosis was induced by 4.25% high glucose peritoneal dialysis fluid (PDF). The rats were randomly divided into 4 groups:the control group, the saline group, the peritoneal fibrosis group, and the probucol group. A 4 hour peritoneal equilibration test (PET) was performed 4 weeks later. The peritoneal function and net ultrafiltration (UF) volume were determined. The level of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in peritoneal tissue were examined. The histology of peritoneal membrane was evaluated by light microscopy. E-cadherin and α-smooth muscle actin (α-SMA) protein expression was evaluated by immunohistochemical method and Western blot.Results The mesothelial cells were detached from peritoneal membrane in peritoneal firbosis rats. Comparing with the control rats, the thickness of visceral peritoneum, the level of MDA, and the-SMA protein expression were increased while the net ultrafiltration volume, the level of GSH-Px and E-cadherin protein expression were decreased in peritoneal firbosis rats. All these changes were reversed in the rats treated with probucol.Conclusion Oxidative stress plays an important role in transdifferentiation of peritoneal mesothelial cell in the peritoneal fibrosis rats. Probucol can improve structure and function of peritoneum, and partially reverse the EMT by reducing the oxidative stress.

Objective To observe contents and effect of total flavonoids of acanthopanax senticosus extract on erythrocyte membrane fluidity.Methods The contents of total flavonoids of acanthopanax sentieosus were deter- mined by spectrophotometry,and erythrocyte membrane fluidity and microviscosity were measured by fluorescence polarization technique.Results The total flavonoids contents of acanthopanax senticosus extract and injection were alike.Both of them increased erythrocyte membrane fluidity and lowered microviscosity,and the effect of acan- thopanax senticosus injection was more significant.Conclusion Total flavonoids of acanthopanax senticosus can in- crease erythrocyte membrane fluidity,so that blood viscosity is lowered and hemorheology factors are improved.

Objective To determine the effect of smad anchor for receptor activation (SARA) on renal tubular epithelial to mesenchymal transtion (EMT) induced by high glucose and to investigate the associated mechanism.Methods HK-2 cells were exposed to high glucose (30 mmol/L).HK-2 cells were transfected with the plasmids of wild-type SARA [SARA (WT)] or SARA mutant [SARA with SBD deletion,called SARA (dSBD)] and then was stimulated by high glucose.The gene expression was assayed by real-time PCR and the protein expression was detected by Western blotting.Results During the process of high glucose-induced EMT of HK-2 cells,the gene and protein expression of SARA were down-regulated.The expression of TGF-β1 and Smad3 increased after stimulation of high glucose in HK-2.However,the Smad2 mRNA expression increased while its protein expression was down-regulated in a time-dependent manner.Smad2 and Smad3 were activated by high glucose stimulation and Smad3 kept activation for longer time than Smad2.Compared with high glucose group,over-expression of SARA by transfection of SARA (WT) up-regulated the expression of zona occludens(ZO)1 and down-regulated the expression of vimentin (P＜0.05).However,SARA (dSBD) had no such effects on above expressions.The Smad2 protein expression increased along with the over-expression of SARA.Meanwhile,over-expression of SARA prolonged the activation time of Smad2 and shortened the activation time of Smad3.Conclusions TGF-β1 signaling is activated and SARA expression is down-regulated during the process of high glucose-induced EMT in HK-2 cells.Over-expression of SARA can inhibit the EMT via increase of Smad2 protein expression and longer activation time of Smad2.

Objective To determine the effect of 2 transforming growth factor β1 (TGF-β1) short hairpin RNA (shRNA) expression plasmids (pcDU6-A1-A2 and pcDU6-B1-B2) on proliferation, TGF-β1, connective tissue growth factor (CTGF), and fibronectin (FN) expression induced by human serum albumin (HAS) in HK2 cells. Methods A vector plasmid containing the TGF-β1 shRNA was generated. An HK2 cell line was used in the study. The 2 TGF-β1 shRNA expression plasmids were transfected into cultured HK2 cells by lipofectamine 2000. Cellular proliferation was assessed by tetrazolium salt colorimetry. The semi-quantitative reverse transcriptive PCR was performed to detect the expression of TGF-β1,CTGF, and FN mRNA. Levels of TGF-β1 and FN protein were measured with a sandwich enzyme-linked immunosorbent assay. Results After treating with 5 g/L HAS for 24 hours in HK2 cells, cellular proliferating capacity increased significantly (P＜0.05). The expression levels of TGF-β1, CTGF, and FN mRNA were upregulated in HK2 cells stimulated by 5 g/L HAS, and levels of TGF-β1 and FN protein in the culture supernatant increased (P＜0.05). The introduction of pcDU6-A1-A2 and pcDU6-B1-B2 resulted in significant reduction of cellular proliferation activity, and the expression levels of TGF-β1, CTGF, and FN mRNA were downregulated (P＜0.05). Levels of TGF-β1 and FN protein in the culture supernatant decreased (P＜0.05) after 12 or 24 hours of TGF-β1 shRNA transfection into HK2 cells There was no significant difference in the expression levels of TGF-β1, CTGF, and FN mRNA between the 2 pcDU6 vector plasmid mediated TGF-β1 shRNA groups (P＞0.05). Conclusion pcDU6 vector plasmid mediated TGF-β1 shRNAs could obviously inhibit the expression levels of TGF-β1, CTGF, FN and cellular proliferation stimulated by HAS in HK2 cells, which may be related to the mediation of TGF-β1.

The treatment for locally advanced cervical cancer,the surgical path of cervical cancer and the surgical indications for preserving fertility are closely related to the stage of cervical cancer,which still have great controversies.With the release of the new staging of cervical cancer by the International Union of Obstetricians and Gynecologists(FIGO)in 2018,relevant clinical diagnosis and treatment should adapt to the new staging.This paper introduces the above problems by referring to relevant researches at home and abroad.

OBJECTIVE: To analyse the clinical and laboratory characteristics of antinuclear antibody (ANA) positive rheumatoid arthritis (RA) patients. METHODS: The clinical and laboratory data of 428 RA cases from Department of of Rheumatology and Immunology Peking University Third Hospital from Jan 2013 to Dec 2018 were collected and used to analyse characters between ANA positive group and ANA negative group. T test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. RESULTS: The number of ANA positive group was 231 (54%). The female rate was obviously higher in ANA positive group (82.7% vs. 63.5%, χ²=20.355, P < 0.01). The rate of metatarsophalangeal joints (MTPJs) involvement was lower in ANA positive group (22.1%) than in ANA negative group (33.0) (χ²=6.414, P < 0.05). The incidence of secondary Sjögren's syndrome (sSS) was much higher in ANA positive group(19.5% vs. 4.1%, χ²=23.300, P < 0.01). The positivity of rheumatoid factor (RF), as well as the positivity of anti-cyclic citrullinated peptide(CCP) antibody was much higher in ANA positive group (77.1% vs. 53.8%, χ²=25.743, P < 0.01, 74.9% vs. 59.4%, χ²=11.694, P < 0.01, respectively). The levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) of ANA positive group were higher [(15.1±5.1) g/L vs. (13.8±5.3) g/L, t=2.359, P < 0.05, 1.25 (0.92) g/L vs. 1.05 (0.65) g/L, Z=-3.449, P < 0.01, respectively]. But the levels of hemoglobin (Hb) and platelet (PLT) was lower in ANA positive group[(109.64±17.98) vs. (114.47±18.48) g/L, t=-2.734, P < 0.01; (266.4×10⁹±104.6×10⁹) vs. (295.9×10⁹±100.1×10⁹) /L, t=-2.970, P < 0.01, respectively]. CONCLUSION The incidence of sSS was obviously higher in ANA positive group than in ANA negative group. Serum IgG of ANA positive group was higher, but Hb and PLT were lower.
Antibodies, Antinuclear ; Arthritis, Rheumatoid/epidemiology* ; Autoantibodies ; Female ; Humans ; Laboratories ; Peptides, Cyclic ; Rheumatoid Factor

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87;95％ CI:1.37-2.57;P=0.000),but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63;95％ CI:-0.45-1.72;P=0.26] and overall survival (OS) (MD=-0.67;95％ CI:-2.54-1.20;P=0.49).In the sub analysis,better ORR was obtained with the addition of EGFR (OR=1.75;95％ CI:1.20-2.56;P=0.004) and VEGFR (OR=2.5;95％ CI:1.28-4.87;P=0.007) targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS (MD=l.36;95％ CI:0.29-2.43;P=0.01).No significant differences were observed in the incidences ofneutropenia (OR=1.37;95％ CI:0.89-2.12),thrombocytopenia (OR=l.40;95％ CI:0.83-2.39),anemia (OR=l.21;95％ CI:0.62-2.38),peripheral neuropathy (OR=1.52;95％ CI:0.81-2.88),increased AST/ALT (OR=l.40;95％ CI:0.82-2.39) as well as fatigue (OR=1.65;95％ CI:0.96-2.84) in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present mcta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

OBJECTIVETo analyze the superiorities of acupoint catgut-embedding therapy, discuss its law of clinical application and provide scientific decision-making for clinical treatment.

METHODSLiteratures on acupoint catgut-embedding therapy in the recent 40 years were selected, input, examined and verified, picked up and analyzed by establishing database with the modern computer technology.

RESULTS(1) One thousand and seventy-five literatures were input. It shows that the acupoint catgut-embedding therapy has an extensive application in all departments, especially in the internal department, accounting for 48.54% (50/103) of the total disease category. It has the most extensive application on treatment of epigastric pain, with the frequency of 102 times, and obesity of 74 times. The next is surgery, accounting for 14.56% (15/103). The major application is on low back pain and leg pain with the frequency of 79 times. Psoriasis, with the frequency of 30 times, holds the major application in dermatological department. And blepharoplasty, with the frequency of 30 times, gains the most application in department of ophthalmology and otorhinolaryngology. (2) In the included literatures, selection of adjacent acupoints and distal acupoints are held as the major method of acupoint selection. The adjusted lumbar puncture needle is taken as the major tool for the acupoint catgut-embedding therapy. And catguts of different sizes are adopted for the operation. (3) Analysis of the therapeutic effect shows that acupoint catgut-embedding therapy has obvious effect in all departments, especially in surgery and dermatology, with the total effective rate over 90%.

CONCLUSIONEpigastric pain, obesity, epilepsy, asthma, abdominal pain, facial paralysis and constipation of the internal medicine, low back pain and leg pain of the surgical department, psoriasis of the dermatological department and blepharoplasty of the department of ophthalmology and otorhinolaryngology are considered as the dominant diseases for acupoint catgut-embedding therapy.

Acupuncture Points ; Acupuncture Therapy ; instrumentation ; methods ; Catgut ; utilization ; Facial Paralysis ; therapy ; Humans ; Low Back Pain ; therapy ; Obesity ; therapy