TPOL triggers apoptosis with mitochondrial injury through activating a ROS-dependent p53/p21/p27/Rb/Bax/Cyto C/caspase-mediated signaling

AIM:To explore the influence of ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate(TPOL)on cell apoptosis and its potential mechanism.METHODS:HEK293T cells sensitive to TPOL were treated with different concentrations of TPOL with or without exposure to light radiation,before treatment with various inhibitors,N-acetyl-Lcysteine(NAC),pifithrin-αand Z-DVED-FMK.Cell viability was measured by CCK-8 assay.Annexin V/propidium iodide staining was used to count the number of apoptotic cells.DCFH-DA staining was used to detect reactive oxygen species(ROS)levels,and JC-1 staining was used to assess mitochondrial membrane potential by flow cytometry.The expression of apoptosis-related proteins and cell cycle-regulated molecules was measured by Western blot.RESULTS:TPOL enhanced the apoptosis of HEK293T cells in a dose-dependent manner(P<0.05),with a decrease in Bcl-2 and increases in Bax and cytochrome C(Cyto C),followed by up-regulation of activated caspase-9 and caspase-3,and the cleavage of PARP(P<0.05).The TPOL-enhanced cleavage of caspase-3 and PARP was rescued by Z-DVED-FMK(P<0.01).TPOL also led to a rapid increase in ROS,a reduction in mitochondrial membrane potential,and the release of Cyto C(P<0.01),all of which could be reversed by the ROS scavenger NAC.Moreover,the TPOL-caused alterations in p21,p27,Rb,and CDK2 were also recovered by the p53 inhibitor pifithrin-α(P<0.05).The TPOL-induced changes in Bax,Bcl-2,cleaved caspase-9,activated caspase-3,and cleaved PARP were subsequently rescued by pretreatment with pifithrin-α(P<0.05).CONCLUSION:TPOL can induce cellular apoptosis with ROS-mediated mitochondrial membrane damage through the activation of a ROS-dependent p53/p21/p27/Rb/Bax/Cyto C/caspase-mediated signal axis.

An interpretability model for syndrome differentiation of HBV-ACLF in traditional Chinese medicine using small-sample imbalanced data

Objective Clinical medical record data associated with hepatitis B-related acute-on-chronic liver failure(HBV-ACLF)generally have small sample sizes and a class imbalance.However,most machine learning models are designed based on balanced data and lack interpretability.This study aimed to propose a traditional Chinese medicine(TCM)diagnostic model for HBV-ACLF based on the TCM syndrome differentiation and treatment theory,which is clinically interpretable and highly accurate.Methods We collected medical records from 261 patients diagnosed with HBV-ACLF,including three syndromes:Yang jaundice(214 cases),Yang-Yin jaundice(41 cases),and Yin jaundice(6 cases).To avoid overfitting of the machine learning model,we excluded the cases of Yin jaundice.After data standardization and cleaning,we obtained 255 relevant medical records of Yang jaundice and Yang-Yin jaundice.To address the class imbalance issue,we employed the oversampling method and five machine learning methods,including logistic regression(LR),support vector machine(SVM),decision tree(DT),random forest(RF),and extreme gradient boosting(XGBoost)to construct the syndrome diagnosis models.This study used precision,F1 score,the area under the receiver operating characteristic(ROC)curve(AUC),and accuracy as model evaluation metrics.The model with the best classification performance was selected to extract the diagnostic rule,and its clinical significance was thoroughly analyzed.Furthermore,we proposed a novel multiple-round stable rule extraction(MRSRE)method to obtain a stable rule set of features that can exhibit the model’s clinical interpretability.Results The precision of the five machine learning models built using oversampled balanced data exceeded 0.90.Among these models,the accuracy of RF classification of syndrome types was 0.92,and the mean F1 scores of the two categories of Yang jaundice and Yang-Yin jaundice were 0.93 and 0.94,respectively.Additionally,the AUC was 0.98.The extraction rules of the RF syndrome differentiation model based on the MRSRE method revealed that the common features of Yang jaundice and Yang-Yin jaundice were wiry pulse,yellowing of the urine,skin,and eyes,normal tongue body,healthy sublingual vessel,nausea,oil loathing,and poor appetite.The main features of Yang jaundice were a red tongue body and thickened sublingual vessels,whereas those of Yang-Yin jaundice were a dark tongue body,pale white tongue body,white tongue coating,lack of strength,slippery pulse,light red tongue body,slimy tongue coating,and abdominal distension.This is aligned with the classifications made by TCM experts based on TCM syndrome differentiation and treatment theory.Conclusion Our model can be utilized for differentiating HBV-ACLF syndromes,which has the potential to be applied to generate other clinically interpretable models with high accuracy on clinical data characterized by small sample sizes and a class imbalance.

关于乙肝病毒Ⅱ型研究的初步报告

目前公认人类乙型肝炎病毒仅有一种血清型。近年来,国内虽有对乙肝病毒标志的临床评价,和乙肝病毒分子生物学的发展,但在临床上对某些检验现象仍无恰当解释,如单纯HBsAg阳性、HBsAg和抗-HBs及抗-HBs和抗-HBc同时存在等。本文通过31例患者血清和肝组织经固相放射免疫、斑点和原尾分子杂交、免疫组化双标记等方法的研究,提出在我国存在乙肝病毒Ⅱ型,现报道如下。材料与结果乙肝五项指标试剂盒购自北京同位素研究所,生物素标记HBVDNA探针(原尾杂交)试剂盒购自美国ENzo Biochen Inc,

妊娠合并乙肝的临床分析

乙型病毒性肝炎的感染在世界范围很广泛,全世界HBV感染者约有3亿左右,亚洲、非洲有色人种感染率最高,我国人口HBSAg携带率约10%,男多于女,孕妇产前检查HBSAg阳性率为6%-15%,此为传播乙型肝炎的重要危险因素,本文试图通过161例孕妇合并乙肝的临床表现进行分析,探讨乙肝对孕妇及胎儿的影响,做好对乙肝传播的预防工作.

8 466例患者输血前或手术前四项感染性指标的检测结果分析

目的分析8466例患者输血前或手术前四项感染性指标的检测结果。方法回顾性分析2017年1月至2017年12月我院8466例输血前或手术前患者四项感染性指标的检测结果,统计分析各项指标的阳性率。抗-HIV(1/2)、抗-TP和抗-HCV均采用ELISA法进行检测,HBsAg采用化学放光法检测。结果8466例患者抗-HIV1/2、抗-TP、抗-HCV和HBsAg的阳性率分别为0.86%、3.26%、1.10%和19.54%。男性患者抗-HIV(1/2)、抗-TP、HBsAg阳性率均高于女性患者(P<0.05)。部分患者在存在两项或三项指标同时阳性的混合感染,其中以抗-TP和HBsAg同时阳性最为多见,另有5例患者存在3项指标同时阳性。结论输血前或手术前对患者进行感染性疾病指标的检测,对了解患者的感染状况、缓和医患关系和防止医院感染具有重要意义。

东北地区黄牛不同组织中HBsAg.HBeAg分布情况调查

用ELISA方法检测43头东北黄牛血清、肝脏和肌肉中乙型肝炎的HBsAg和HBeAg结果表明,同一动物不同组织中两种抗原分布不同,HBsAg阳性:肝脏27.9％、肌肉9.3％、血清2.3％;HBeAg阳性:肝脏11.6％而肌肉和血清均为阴性。实验结果说明:在检测动物乙型肝炎时,应测试两种指标,在动物与人类乙型肝炎相关性研究中,动物肝脏应当引起人们的高度警觉。

茵栀清肝汤联合恩替卡韦治疗HBeAg阳性慢性乙型肝炎临床观察

目的:观察茵栀清肝汤治疗HBeAg阳性慢性乙型肝炎患者临床疗效。方法:将83例湿热型HBeAg阳性慢性乙型肝炎患者,随机分为两组,治疗组42例患者采用茵栀清肝汤联合恩替卡韦治疗,对照组41例单用恩替卡韦治疗,疗程均为144周。观察两组患者HBeAg阴转率,HBeAg/HBe Ab血清学转换率,HBV DNA阴转率,血清ALT、AST复常率及中医临床症候及体征变化情况。结果:治疗组患者血清学HBeAg阴转率、HBeAg/HBe Ab血清学转换率,HBV DNA转阴率及中医临床症候改善率均优于对照组,P <0. 05;两组患者ALT、AST复常率比较,差异有显著性意义(P <0. 05)。结论:茵栀清肝汤联合恩替卡韦治疗HBeAg阳性慢性乙型肝炎,可提高HBeAg血清学转换率,抑制HBV DNA复制,能较好改善患者临床症状及体征。

The Effect of Active Oxygen on the Activity of ACC Synthase Induced by Exogenous IAA

During the course of mungbean (Phaseolus radiatus L.) germination, the rate of ethylene production and the activity of ACC synthase (1_aminocyclopropane_1_carboxylic acid synthase, EC4.4.1.4) began to increase in the 5th day of germination, and reached its peak in the 10th day and then decreased. The ethylene production and the activity of ACC synthase were obviously promoted by 10 μmol/L exogenous IAA (indole_3_acetic acid). The production of superoxide radical (O -· 2) and hydrogen peroxide (H 2O 2) were also promoted by exogenous IAA, suggesting that there was some relationship between active oxygen production and the activity of ACC synthase induced by exogenous IAA. The production of ethylene and the activity of ACC synthase increased dramatically when the seedlings were treated with exogenous O -· 2, whereas the exogenous H 2O 2 had no effects on the production of ethylene and the activity of ACC synthase. Exogenous SOD (superoxide dismutase, one scavenger of O -· 2) could inhibit the production of ethylene and the activity of ACC synthase, but exogenous CAT (catalase) could not. So it was possible that IAA would stimulate the activity of ACC synthase by inducing the production of O -· 2 in germinating mungbean seedlings, and this might be one of the regulating mechanism of ethylene synthesis in higher plants; the production of H 2O 2 induced by IAA was not the cause of the increase of the activity of ACC synthase and the production of ethylene.

Preparation and sensing performance of petal-like RuO_2 modified ZnO nanosheets via a facile solvothermal and calcination method

Petal-like ZnO nanosheets were synthesized with zinc nitrate hexahydrate and sodium hydroxide as starting materials in ammonia and ethanol mixture solution. RuO2 modified ZnO nanosheets were also prepared by a calcination route. The as-prepared products were characterized by X-ray powder diffraction and field emission scanning electron microscopy, and its specific BET surface area was calculated by nitrogen adsorption method. The sensitivity, response and recovery speed were examined. The results show that RuO2 modified petal-like ZnO based sensor exhibits a high sensitivity, a low detection limit, fast response and recovery properties to ethanol and acetone. The sensitivities of the RuO2 modified petal-like ZnO based sensor to 100×10^-6 ethanol and acetone at 360 °C are 33 and 67, respectively. The response and recovery times of the sensor are 4 s and 9 s to 10×10^-6 ethanol, and are 3 s and 10 s to 10×10^-6 acetone, respectively.

Role of Antivirus Therapy in Treatment of Hepatocellular Carcinoma with Chronic Hepatitis B Infection

Objective： To observe the recurrence and prognosis of hepatocellular carcinoma （HCC） patients coexisting with chronic hepatitis B infection with active virus replication after receiving antivirus therapy using lamivudine and thymosin α1 （Tα1） postoperatively. Methods： From Jan. 2000 to Dec. 2003, 70 patients with HCC coexisting chronic hepatitis B infection with active virus replication were prospectively divided into two groups： control group （n=35） received hepatectomy only; treatment group （n=35） received hepatectomy and lamivudine plus Tα1 therapy postoperatively. The suppression of HBV-DNA, HBeAg seroconverted rate, tumor recurrent rate and the median survival for the two groups were observed and calculated. Results： In treatment group and control group, the 2-year HBV-DNA suppression rate was 100% vs. 4% （P=0.0000）; HBeAg seroconverted rate was 73.0% vs. 7.5% （P〈0.05）; the recurrent rate was 10.0 vs 6.5 months （P=0.0032）; the median survival time was 12.5 vs. 6.0 months （P=0.0023）, respectively. Conclusion： Antivirus therapy using lamivudine and Tα1 postoperatively may suppress the HBV reaction, delay the recurrent time and prolong the survival for HCC patients coexisting chronic HBV infection with active virus replication.

80例输血患者输血前抗-HCV、HB-sAg、抗-TP和抗-HIV检出情况分析

目的探讨80例输血患者输血前丙型肝炎病毒抗体(hepatitis C virus,HCV)、乙型肝炎表面抗原抗体(hapatitis B surface antigen,HBsAg)、梅毒螺旋体抗体(treponema pallidum,-TP)和人类免疫缺陷病毒抗体(human immuno-deficiency virus,HIV)检出情况。方法选取2018年2月至2019年2月本院收治的80例输血患者作为研究对象,输血前对所有患者分别进行抗-HCV、HB-sAg、抗-TP和抗-HIV的检测,比较4种感染性指标阳性检出率和多重感染情况。结果 80例输血患者中,抗-HCV阳性检出率为15.00%,HB-sAg阳性检出率为18.75%,抗-TP阳性检出率为13.75%,抗-HIV阳性检出率为10.00%;HB-sAg和抗-TP同时阳性是多种感染的主要类型,阳性检出率为5.00%(4/80)。结论加强检测输血患者输血前感染性指标,可帮助医护人员了解输血患者经血传染疾病感染情况。

Effect of pore size in mesoporous MnO_2 prepared by KIT-6 aged at different temperatures on ethanol catalytic oxidation

KIT‐6 mesoporous silica aged at 40,100,and 150°C were used as hard templates to prepare different mesoporous MnO2 catalysts,marked as Mn‐40,Mn‐100,and Mn‐150,respectively.The catalytic activities of these catalysts and the effect of pore sizes on ethanol catalytic oxidation were investigated.Mn‐40,Mn‐100,and Mn‐150 have triple,double,and single pore systems,respectively.On decreasing the aging temperature of KIT‐6,the pore sizes of KIT‐6 decrease and that of mesoporous MnO2 catalysts increase.The pore sizes and catalytic activities increase in the order:Mn‐40>Mn‐100>Mn‐150.Mn‐40 catalyst has a higher TOF(0.11 s–1 at 120°C)and the best catalytic activity for ethanol oxidation because of a bigger pore size with three pore systems with maximum distribution at 1.9,3.4,and 6.6 nm,decrease in symmetry and degree of order,more surface lattice oxygen species,oxygen vacancies resulting from more Mn3+ions,and better low‐temperature reducibility.

慢性乙型肝炎患者不同基因型的临床特征比较

目的:比较分析B、C基因型慢性乙肝患者(CHB)临床特征的差异。方法:选择经基因型检测确定为B、C基因型的慢性乙型肝炎患者共102例,检验其肝功能相关指标及血清病毒标志物,统计重型肝炎、肝硬化、肝细胞癌和HBeAg阳性发生率;对其中55例未并发重型肝炎、肝硬化和肝细胞癌而同意进行肝穿刺的患者获取肝组织后确定肝病理炎症分级及纤维化分期。最后比较B、C基因型患者之间以上指标的统计学差异。结果:(1)C基因型乙肝患者的白蛋白、前白蛋白均低于B型患者,而谷丙转氨酶、HBV DNA载量及肝纤维指标HA(透明质酸)、CIV(IV型胶原蛋白)、PCⅢ(Ⅲ型前胶原)、LN(层粘连蛋白)水平均高于B型患者;(2)在病理组织检查较高的炎症分级和纤维分期中C型患者的发生率均高于B型患者;而且随肝组织病理炎症分级和纤维化分期的上升,C基因型患者的发生率增加;(3)C型患者重型肝炎、肝硬化、原发性肝癌等的发生率及HBeAg阳性率均高于B型患者。结论:B、C两种基因型乙肝患者临床特征明显不同,C型患者的肝细胞炎性损伤程度及肝组织纤维化程度高于B型患者,血清病毒标志物水平明显高于B型患者,重型肝炎、慢性晚期肝病的发生率高于B型患者。总之,C型患者病情重、预后差。

Acetylation of Chinese bamboo flour and thermoplasticity

Chinese bamboo flour was chemically modified by acetylation with acetic anhydride by using trichloroacetic acid as an activation agent and the optimized condition for acetylation of bamboo flour was determined as the trichloroacetic acid amount 6.0 g per 1.5-g bamboo flour, ultrasosonication duration 40 min and the reaction time 1 h at 65℃. The composition, microstructure and thermal behavior of acetylated bamboo flour were preliminarily characterized by FT-IR, DSC and SEM etc. The acetylated bamboo flour can be molded into sheets at 130℃ and 10 MPa, indicating the modified bamboo flour possesses thermalplastic performance.

Formability of AA5052/polyethylene/AA5052 sandwich sheets

The formability of AA5052/polyethylene/AA5052 sandwich sheets was experimentally studied. Three kinds of AA5052/polyethylene/AA5052 sandwich specimens with different thicknesses of core materials were prepared by the hot pressing adhesive method. Then, the uniaxial tensile tests were conducted to investigate the mechanical properties of AA5052/polyethylene/ AA5052 sandwich sheets, and the stretching tests were carried out to investigate the influences of polymer core thickness on the limit dome height of the sandwich sheet. The forming limit curves for three kinds of sandwich sheets were obtained. The experimental results show that the forming limit of the AA5052/polyethylene/AA5052 sandwich sheet is higher than that of the monolithic AA5052 sheet, and it increases with increasing the thickness of polyethylene core.

Novel Stilbene Glycosides from Polygonum multiflorum

Two new stilbene glycosides (1 and 2), together with nine known compounds (3-11), were isolated from the water extract of Polygonum multiflorum Thunb. The structures of the new compounds were elucidated by their chemical properties and spectroscopic analyses, including extensive 2D NMR experiments. Compound 2 showed strong DNA cleavage activity, and compounds 1, 2 and 10 (2, 3, 4′, 5_tetrahydroxy_ trans _stilbene_2_O_β_ D _glucopyranoside) exhibited significant inhibition of lipid peroxidation.

肝纤Ⅰ号联合超氧化物歧化酶脂质体对慢性乙型肝炎患者肝纤维化的治疗作用

目的：探讨联合应用肝纤Ⅰ号和超氧化物歧化酶脂质体（ＳＯＤＬ）对慢性乙型肝炎患者肝纤维化的治疗作用。方法：６３例慢性乙型肝炎患者随机分为治疗组（３３例）和对照组（３０例）。对照组用常规方法治疗，治疗组在常规方法的基础上加用肝纤Ⅰ号和ＳＯＤＬ。观察两组患者治疗前后血清肝纤维化指标（ＰＣⅢ、ＨＡ、ＬＮ）变化，同时观察肝功能、自由基、淋巴细胞亚群及乙型肝炎病毒标志物的变化。结果：治疗组在治疗前后血清ＰＣⅢ、ＨＡ、ＬＮ明显下降，而对照组无显著性变化，其中ＨＢＶＤＮＡ阴转者ＰＣⅢ、ＨＡ、ＬＮ下降最为显著。治疗组肝功能恢复程度、自由基及淋巴细胞亚群的改变也明显优于对照组。结论：两药联合应用对慢性乙型肝炎患者肝纤维化有较好的治疗作用，其抗肝纤维化作用与抗病毒作用密切相关。

Study on Safe Dosage of Imazethapyr for an Imazethapyr Resistant Millet Variety and Its Effect on Weed Control

[Objective] This study aimed to investigate the safe dosage of imazethapyr for an imazethapyr resistant millet variety and its effect on weed control. [Method] The Imazethapyr resistant millet ＂M1508＂ was used as the experimental material and the experiment was arranged in a split plot design with two factors： herbicide application time and herbicide dosage. Application time was taken as the main plot with six treatments： A1 （preemergence treatment）, A2 （postemergence treatment on the 3rd d）, A3 （postemergence treatment on the 6th d）, A4 （postemergence treatment on the 9th d）, A5 （postemergence treatment on the 12th d）, A6 （postemergence treatment on the 15th d）; spraying dosage（B） with nine treatments： B1 （0 ml/hm2 , taking water as control）, B2 （750 ml/hm2 ）, B3 （1 125 ml/hm2 ）, B4 （1 500 ml/hm2 ）, B5 （2 250 ml/hm2 ）, B6 （3 000 ml/hm2 ）, B7 （4 500 ml/hm2 ）, B8 （6 000 ml/hm2）, B9 （7 500 ml/hm2 ）; water was added at 675 kg/hm2 . [Result] Imazethapyr showed a good herbicidal effect, and the imazethapyr resistant new variety M1508 also had a high drug resistance; the dosage range of 750 -7 500 ml/hm2 was safe for millet; considering the weed control efficacy, the yield and weeding cost comprehensively, postemergence treatment on the 6th day at 1 500 -2 250 ml/hm2 was the best for herbicide application. [Conclusion] Matched chemical weeding techniques to imazethapyr resistant millet varieties were preliminarily identified, and the efficacy of imazethapyr on weed control and its security on millet were investigated, providing references for the application and promotion of imazethapyr resistant millet varieties.

Target-site Mechanisms Involved in Annual Bluegrass(Poa annua L.) Tolerance to Fenoxaprop-P-ethyl

Annual bluegrass （Poa annua L.） was found to be tolerant to fenoxaprop- P-ethyl as well as quizalofop-P-ethyl, haloxyfop-R-methyl, clodinafop-propargyl, fluaz- ifop-P-butyl, cyhalofop-butyl, sethoxydim and tralkoxydim, whereas it was sensitive to clethodim and tepraloxydim. The acetyI-CoA carboxylase （ACCase） IC50 values of five P. annua biotypes were 10.46 to 11.98-fold higher than the susceptible Japanese foxtail （Alopecurus japonicus Steud.）. The presence of the polymorphic lie and Leu at 1 781, which the presence of Leu at 1 781 had been reported to be in- volved in the resistance of grass weeds to ACCase inhibitors, was subsequently i- dentified in the ACCase of P. annua. Furthermore, the expression level of gene that encoding P. annua ACCase was found to be approximately 4.67 to 7.37-fold higher than A. japonicus, possibly explaining the P. annua target site tolerance to fenoxaprop-P-ethyl.

Conversion of Pretreated Biomass into Levulinic Acid via Continuous Extraction at Atmosphere Pressure

Conversion of biomass to chemicals or fuels under mild condition is still a challenge. As a platform molecule for chemicals and fuels, levulinic acid （LA） has been prepared by lique-faction of biomass at high pressure. In order to carry out the conversion from wheat straw to LA at atmosphere pressure, continuous extraction of the reactive system by an organic solvent with a higher density than that of water was utilized for degradation of pretreated biomass. Yields of LA were measured by means of gas chromatography-mass spectrometry and nuclear magnetic resonance. The results revealed that a maximum yield of 30.66% of LA can be obtained from wheat straw. In addition, the effects of biomass pretreated conditions on the LA conversion have been studied. The study provides a new route to convert biomass to valuable chemicals at atmosphere pressure.