1.Association study of α-synuclein gene polymorphism and non motor symptoms in Parkinson's disease
Guoping WU ; Dayong WAN ; Wenyan KANG ; Jun LIU
Chinese Journal of Neurology 2015;48(10):870-875
Objective To investigate the association between the single nucleotide polymorphisms (SNPs) rs894278 and rs11931074 of α-synuclein (SNCA) and non motor symptoms in Parkinson' s disease (PD).Methods One hundred and twenty PD patients and 100 healthy controls enrolled from Tonglu Hospital Affiliated to Ruijin Hospital and Ruijin Hospital,Shanghai Jiaotong University School of Medicine from 2012 to 2014 were recruited and the motor subscale of the Unified Parkinson' s Disease Rating Scale Ⅲ (UPDRS-Ⅲ) was used to evaluate motor function.The Mini-Mental State Examination (MMSE),17-item Hamilton Rating Scale (HAMD-17),the Rapid Eye Movement Behavior Disorder Screening Questionnaire (RBDSQ) and the ROME-Ⅲ criteria for chronic constipation were used to evaluate non motor symptoms.SNCA SNPs (rs894278,rs11931074) were genotyped by direct sequencing.Results There was no statistically significant difference in age,sex,non motor symptoms scores among the three genotypes of the two SNPs in control group.There was no statistically significant difference in age,sex,UPDRS-Ⅲ scores and Hoehn-Yahr stage among the three genotypes of the two SNPs in PD group.The results demonstrated that there was no association between the two SNPs and RBDSQ scores,HAMD-17 scores,MMSE scores and constipation in PD patients.However,additional analysis showed that patients with GG rs894278 had a greater proportion of clinical probable RBD than those with GT and TT types (GG 52.2%,12/23;GT 18.2%,10/55;TT 21.4%,9/42;x2 =9.254,P=0.002;x2 =6.424,P=0.005).In Logistic regression analyses adjusting for age and sex,we observed that rs894278 GG genotype could increase the risk of RBD in PD patients (OR =5.367,95% CI =1.607-17.925,P =0.006).There was no association of RBD with allelic and genotypic distributions of SNCA rs11931074.Conclusion The results indicate that the rs894278 polymorphism correlates with RBD,while rs11931074 does not.
2.Clinical effect and nursing care of ultrasonic atomization with traditional Chinese medicine on wound healing after anorectal operation patients
Lele TANG ; Wenyan WAN ; Jiazhi GAO
Chinese Journal of Modern Nursing 2015;21(10):1136-1138
Objective To discuss the clinical effect and appropriate nursing for wound healing after anorectal operation with ultrasonic atomization in traditional Chinese medicine. Methods A clinical research method for random distribution was conducted. Totals of 120 anorectal surgery cases matched with the inclusion criteria were randomly divided into the observation group ( TCM group ) of 60 cases, and the control group ( potassium permanganate group ) of 60 cases. The average disappear time of post-operative symptoms were respectively observed and the number of days of wound healing were respectively recorded between the two groups. Results In the observation group, the average disappear time of post-operative symptoms of pain, edema, cataclysm, hematochezia and the healing time were (8. 20 ± 1. 56), (4. 33 ± 0. 46), (7. 56 ± 1. 38), (3.67 ±1.49) and (14.17 ±1.58)days, which were significantly shorter than those of the control group (t=4. 313, 3. 765, 4. 983, 3. 038, 7. 560, respectively;P<0. 05). The post-operative healing rate of the 7th and 14th day were (53. 66 ± 1. 88)% and (89. 46 ± 2. 13)%, which were significantly higher than those of the control group (t=6. 89, 15. 08, respectively;P<0. 01). In the observation group, 38 cases were significantly effective, 20 cases were effective, and 2 cases had no therapeutic effect, which were significantly better than those of the control group (Z =21. 76, P <0. 01). Conclusions Fumigation with ultrasonic atomization of traditional Chinese medicine can improve post-operative symptoms and promote wound healing after anorectal operation.
3.Determination of chlorinated paraffins in PM2.5 by QuEChERS combined with ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry
Wenyan YAN ; Chao WANG ; Juan LIU ; Yibin SUN ; Wen GU ; Yifu LU ; Ke FANG ; Yi WAN ; Song TANG
Journal of Environmental and Occupational Medicine 2024;41(10):1087-1094
Background Previous research on chlorinated paraffins (CPs) in fine particulate matter (PM2.5) has predominantly focused on short- and medium-chain chlorinated paraffins (SCCPs and MCCPs), and few studies could simultaneously determine short-, medium-, and long-chain chlorinated paraffins (LCCPs). Simultaneous extraction and determination of SCCPs, MCCPs, and LCCPs in PM2.5 could provide technical support for their environmental monitoring and human health risk assessment. Objective To establish a method based on QUEChERS pretreatment method in conjunction with ultra-performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry for simultaneously determining the levels of SCCPs, MCCPs, and LCCPs in PM2.5. Methods The extraction solvents, extraction salts, and extraction steps of a QuEChERS method were optimized. The extraction efficiencies of the target substances were compared under 4 extraction solvents [acetonitrile, dichloromethane, and n-hexane solvents in sequence; acetonitrile: dichloromethane: n-hexane = 1: 1: 2 (v/v/v) mixed solvent; 1% acetic acid-acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent; acetonitrile: dichloromethane: n-hexane = 1: 1: 1 (v/v/v) mixed solvent], 2 dehydrated salts (anhydrous MgSO4+NaCl and anhydrous Na2SO4+NaCl), 2 purification salts (C18 and PSA), and 4 vortex time (5, 7.5, 10, and 12.5 min) conditions. Then internal standard was utilized to estimate linear range and detection limit of the refined QuEChERS approach. Results The linearities of SCCPs, MCCPs, and LCCPs were good in the range of 10~
4.Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy.
Xin YUE ; Tingyu LIU ; Xuecen WANG ; Weijian WU ; Gesi WEN ; Yang YI ; Jiaxin WU ; Ziyang WANG ; Weixiang ZHAN ; Ruirui WU ; Yuan MENG ; Zhirui CAO ; Liyuan LE ; Wenyan QIU ; Xiaoyue ZHANG ; Zhenyu LI ; Yong CHEN ; Guohui WAN ; Xianzhang BU ; Zhenwei PENG ; Ran-Yi LIU
Acta Pharmaceutica Sinica B 2023;13(8):3382-3399
Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.