基于扶正解毒消积方的中西医结合方案治疗原发性肝癌的疗效分析

目的探讨基于扶正解毒消积方的中西医结合方案对原发性肝癌的临床疗效及预后的影响。方法将68例原发性肝癌患者分为中西医结合组(西医综合治疗+扶正解毒消积方加减)和西医治疗组(西医综合治疗)各34例,观察两组治疗前后肝功能、甲胎蛋白和凝血酶原活动度情况以及实体瘤疗效、肝功能Child-Pugh分级及生存率。结果治疗后中西医结合组患者血清白蛋白(ALB)水平较治疗前明显升高,且高于西医治疗组治疗后(P<0.05)。治疗后中西医结合组实体瘤缓解率(33.33%)和稳定率(87.88%)均高于西医治疗组的17.24%和62.68%(P<0.05)。两组治疗后Child-Pugh分级比较差异无统计学意义(P>0.05)。治疗后中西医结合组生存率为97.1%,西医治疗组为85.3%,两组比较差异无统计学意义(P>0.05)。结论基于扶正解毒消积方的中西医结合方案治疗能够控制原发性肝癌的复发和进展,提高患者的生存时间。

扶正解毒消积方联合肝动脉化疗栓塞术对原发性肝癌气阴两虚、毒瘀蕴积证患者免疫功能及生存情况的影响

目的观察扶正解毒消积方对行肝动脉化疗栓塞术(TACE)的原发性肝癌气阴两虚、毒瘀蕴积证患者免疫功能及生存情况的影响。方法选取120例原发性肝癌气阴两虚、毒瘀蕴积证患者作为研究对象,均为TACE初治患者,根据患者意愿分为中西医组56例和西医组64例。西医组采用TACE和对症支持治疗,每位患者行TACE治疗2~4次,每次间隔时间为6~8周。中西医组在TACE治疗同时加用扶正解毒消积方,每日1剂,3个月为1个疗程,连服3个疗程。比较两组患者治疗前后T细胞免疫功能相关指标(CD3^(+)、CD4^(+)、CD8^(+)及CD4/CD8)、血清甲胎蛋白(AFP)水平、肿瘤无进展生存期,分析患者复发时间影响因素。结果西医组患者治疗后CD3^(+)、CD4^(+)明显低于治疗前(P<0.05)。治疗后中西医组CD3^(+)、CD4^(+)水平明显高于同期西医组,而血清AFP水平明显低于同时期西医组(P<0.01)。两组患者治疗后,中西医组无进展生存期在3个月、6个月、9个月、12个月、18个月各时段病例数均明显高于同时期西医组(P<0.01)。中西医组的复发时间为8.5(4.00,12.00)个月,西医组的复发时间为2.00(1.00,3.00)个月。中西医组的复发时间长于西医组(P<0.01)。复发时间影响因素分析显示,组别和BCLC分期是复发时间的影响因素,西医组的复发风险是中西医组的3.483倍(OR=3.483,95%CI为2.272~5.340),BCLC分期每进展一期,复发风险上升1.758倍(OR=1.758,95%CI为1.104~2.800)。结论扶正解毒消积方可改善TACE初治的原发性肝癌气阴两虚、毒瘀蕴积证患者免疫功能,增强抗肿瘤能力,抑制短期复发,延长无进展生存期,从而延缓病情进展。

扶正解毒消积方加减联合西医治疗乙型肝炎相关原发性肝癌气阴不足、毒瘀蕴积证80例临床观察

目的观察扶正解毒消积方加减联合西医治疗乙型肝炎相关原发性肝癌气阴不足、毒瘀蕴积证患者的疗效及安全性。方法163例乙型肝炎相关原发性肝癌气阴不足、毒瘀蕴积证患者随机分为中西医结合组80例,西医组83例。西医组给予抗病毒、内科综合治疗及肝动脉化疗栓塞术(TACE)治疗,中西医结合组在西医组基础上加用扶正解毒消积方加减口服,每日1剂。两组均治疗52周,随访52周。比较两组患者一年生存率及二年生存率,并进行实体瘤疗效判定,于治疗前及治疗第12、24、36、52周检测肝功能[包括丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、总胆红素(TBiL)、白蛋白(ALB)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)]、血肌酐(Scr)、甲胎蛋白(AFP)水平,并记录不良反应。结果中西医结合组巴塞罗那临床肝癌分期(BCLC分期)为A期患者二年生存率为86.5%,高于西医组的65.0%;B期患者一年生存率为80.0%,高于西医组的66.7%(P<0.05)。中西医结合组实体瘤疗效缓解率为46.6%,稳定率为78.1%,均高于西医组的30.1%、56.2%(P<0.05)。治疗第12、24、36、52周,两组患者ALT、AST、TBiL、ALP、GGT、AFP水平均较本组治疗前降低(P<0.05或P<0.01),且治疗第36、52周各指标中西医结合组较西医组降低更显著(P<0.05或P<0.01)。两组均未出现与药物相关的不良反应。结论扶正解毒消积方加减联合西医治疗能提高乙型肝炎相关原发性肝癌气阴不足、毒瘀蕴积证BCLC分期为A期和B期患者的生存率,改善肝功能,优于单纯的西医治疗,且具有较好的安全性。

Toxicity and bioaccumulation of heavy metals in Phanerochaete chrysosporium

The responses of the growth and metabolism activity of Phanerochaete chrysosporium （P. chrysosporium） to cadmium （Cd）, lead （Pb） and their combined pollution stress, were investigated in plate and liquid culture conditions. The diameter of colony, biomass ofP. chrysosporium, ligninolytic enzyme activities and bioaccumulation quantity of heavy metals were detected. The results indicated that Cd was more toxic than Pb to P. chrysosporium and the toxicity of Cd and Pb to P. chrysosporium was further strengthened under Cd＋Pb combined pollution in different culture conditions. Heavy metals Cd and Pb had indirect influence on the production of ligninolytic enzymes by directly affecting the fungal growth and metabolic activity, and by another way in liquid culture. In addition, the results provided an evidence of the accumulation of Cd and Pb on the mycelia ofP. chrysosporium.

扶正解毒消积方辅助治疗早中期原发性肝癌患者2年生存情况回顾性分析及对NLR的影响

目的探讨扶正解毒消积方对早中期原发性肝癌患者2年生存情况的影响及可能作用机制。方法回顾性分析首都医科大学附属北京地坛医院中西医结合中心首次确诊的原发性肝癌且随访满2年(24个月)的早中期患者76例,根据治疗方式的不同分为扶正解毒消积方组55例和西医治疗组21例。比较两组患者2年病死率,治疗前及治疗6、12、18、24个月时中性粒细胞与淋巴细胞比值(NLR)。结果扶正解毒消积方组2年病死率为12.7%,明显低于西医治疗组的33.3%(P<0.05)。扶正解毒消积方组在治疗6、12、18个月时NLR水平与治疗前比较差异无统计学意义(P>0.05),而治疗24个月与治疗前比较明显升高(P<0.05)。西医治疗组在治疗6、12、18、24个月与治疗前比较NLR均明显升高(P<0.05)。扶正解毒消积方组治疗6、12、18、24个月时NLR水平均明显低于同时间西医治疗组(P<0.05)。结论扶正解毒消积方能提高早中期原发性肝癌患者两年生存率,调节维持NLR水平可能是其重要作用机制之一。

Heavy Metal Bioaccumulation and Toxicity with Special Reference to Microalgae

The bioaccumulation and toxicity of heavy metals were reviewed with special reference to microalgae, the key compo- nent of the food web in aquatic ecosystems. Heavy metals enter algal cells either by means of active transport or by endocytosis through chelating proteins and affect various physiological and biochemical processes of the algae. The toxicity primarily results from their binding to the sulphydryl groups in proteins or disrupting protein structure or displacing essential elements. Metals can break the oxidative balance of the algae, inducing antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and ascorbate peroxidase (APX). The amount of oxidized proteins and lipids in the algal cells thus indicates the severity of the stress. Algal tolerance to heavy metal is highly dependent upon the defense response against the probable oxidative damages. Pro- duction of binding factors and proteins, exclusion of metals from cells by ion-selective transporters and excretion or compartmen- talization have been suggested with regard to reducing heavy metal toxicity. However, a comprehensive description on the mecha- nisms underlining metal toxicity of microalgae and gaining tolerance is yet to be elaborated.

Aquaporins:Their role in cholestatic liver disease

This review focuses on current knowledge on hepato-cyte aquaporins(AQPs)and their significance in bile formation and cholestasis.Canalicular bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate water flow in response to the osmotic gradients created. During choleresis,hepatocytes rapidly increase their canalicular membrane water permeability by modulating the abundance of AQP8.The question was raised as to whether the opposite process,i.e.a decreased canalicular AQP8 expression would contribute to the development of cholestasis.Studies in several experimental models of cholestasis,such as extrahepatic obstructive cholestasis,estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition,biophysical studies in canalicular plasma membranes revealed decreased water permeability associated with AQP8 protein downregulation.The combined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water flow.Thus cholestasis may result from a mutual occurrence of impaired solute transport and decreased water permeability.

Persistence of malachite green and leucomalachite green in perch (Lateolabrax japonicus)

The persistence of malachite green (MG), and its metabolite leucomalachite green (LMG), in fish tissues is still unclear, leading to many trade disputes. In this research, we established and evaluated an HPLC method that could detect MG and LMG simultaneously, and then investigated the persistence of these two toxins in the tissues of juvenile perch (Lateolabrax japonicus) post sub-chronic MG exposure at 1.0 mg/L. Exposure lasted for 2 h everyday and was repeated six times. The perch were then placed in MG-free seawater for 100 d to eliminate the toxins. Results show that MG accumulated in the tissues, including the gills, liver, muscle, blood and viscera, and then was metabolized rapidly to LMG. The concentrations of these two toxins increased significantly with the accumulation process. In general, the highest concentrations of MG and LMG in all tissue exceeded 1 000 μg/kg, except for MG in the muscle. The order of accumulation levels (highest to lowest) of MG was gill>blood>liver>viscera>muscle, while that of LMG was liver>blood>gill>viscera>muscle. High levels of MG or LMG could persist for several hours but decreased rapidly during the elimination process. The concentration of LMG was much higher than that of MG during the experiment, especially in the gill, liver and blood. Therefore, the three tissues play important roles in toxin accumulation, biotransformation, and elimination. Although the MG and LMG concentrations in muscle were much lower than in other tissues, the content still exceeded the European minimum required performance limit (MRPL), even after 2 400 h (100 d) of elimination. This demonstrates that it is extremely difficult to eliminate MG and LMG from tissues of perch, and therefore use of these toxins is of concern to public health.

Studies on the Time of Accumulation and Elimination of Alexandrium tamarense Toxins in Argopectens irradias

Using a PSP （paralytic shellfish poisoning） toxin-producing strain of4lexandrium tamarense, it studied the timing of toxin accumulation and elimination of PSP toxins in Argopectens irradias. The PSP toxicity was studied by following the standard PSP mouse bioassay developed by the Association of Official Analytical Chemists （AOAC）. Alexandrium tamarense was cultured to an average density of 1.26 × 10^4/mL for a total of about 50 L culture. The toxicity of the alga was 2.18 ×10^-6 MU/cell. The results show that PSP content increased with time in both visceral and muscle tissue during a two-week accumulation period during which scallops were fed with ,4. tamarense. The average toxin level in scallop＇s viscera was 49.4 MU/g, with an average of 10.0 MU/g in muscle tissue. This level is 2.5 times higher than the sanitation standard （4.0 MU/g of muscles）. The highest value was 61.0 MU/g in the viscera. In summary, the viscera accumulated greater concentrations of toxin than muscle tissue. Scallops that had accumulated toxins were transplanted for two weeks into a field environment containing no toxic algae. The PSP content of the scallops decreased to 7.9 MU/g viscera and 1.6 MU/g muscles two weeks after being transplanted, but did not reach the sanitation standard. Under the experimental conditions, the toxin depuration rate of shellfish toxin was 12% daily. This study worked toward the development of a sanitary shellfish industry and better management of PSP toxin-impacted shellfish in China.

Novel insight into mechanisms of cholestatic liver injury

Cholestasis results in a buildup of bile acids in serum and in hepatocytes.Early studies into the mechanisms of cholestatic liver injury strongly implicated bile acidinduced apoptosis as the major cause of hepatocellular injury.Recent work has focused both on the role of bile acids in cell signaling as well as the role of sterile inflammation in the pathophysiology.Advances in modern analytical methodology have allowed for more accurate measuring of bile acid concentrations in serum,liver,and bile to very low levels of detection.Interestingly,toxic bile acid levels are seemingly far lower than previously hypothesized.The initial hypothesis has been based largely upon the exposure of μmol/L concentrations of toxic bile acids and bile salts to primary hepatocytes in cell culture,the possibility that in vivo bile acid concentrations may be far lower than the observed in vitro toxicity has far reaching implications in the mechanism of injury.This review will focus on both how different bile acids and different bile acid concentrations can affect hepatocytes during cholestasis,and additionally provide insight into how these data support recent hypotheses that cholestatic liver injury may not occur through direct bile acid-induced apoptosis,but may involve largely inflammatory cell-mediated liver cell necrosis.

Factors predicting occurrence and prognosis of hepatitis-B-virus-related hepatocellular carcinoma

Primary liver cancer is an important cause of cancer death, and hepatocellular carcinoma （HCC） accounts for 70%-85% of total liver cancer worldwide. Chronic hepatitis B virus （HBV） infection contributes to 〉 75% of HCC cases. High serum viral load is the most reliable indicator of viral replication in predicting development of HCC. HBV genotype C is closely associated with HCC in cirrhotic patients aged 〉 50 years, whereas genotype B is associated with development of HCC in non-cirrhotic young patients and postoperative relapse of HCC. Different HBV subgenotypes have distinct patterns of mutations, which are clearly associated with increased risk of HCC. Mutations accumulate during chronic HBV infection and predict occurrence of HCC. Chronic inflammation leads to increased frequency of viral mutation via cellular cytidine deaminase induction. Mutations are negatively selected by host immunity, whereas some immuno-escaped HBV mutants are active in hepatocarcinogenesis. Inflammatory pathways contribute to the inflammation-necrosis-regeneration process, ultimately HCC. Their hallmark molecules can predict malignancy in HBV-infected subjects. Continuing inflammation is involved in hepatocarcinogenesis and closely related to recurrence and metastasis. HBV load, genotype C, viral mutations and expression of inflammatory molecules in HBV-related HCC tissues are significantly associated with poor prognosis. Imbalance between intratumoral CD8^＋T cells and regulatory T cells or Thl and Th2 cytokines in peritumoral tissues can predict prognosis of HBV-related HCC. These factors are important for developing active prevention and surveillance of HBV-infected subjects who are more likely to develop HCC, or for tailoring suitable treatment to improve survival or postpone postoperative recurrence of HCC.

原发性肝癌之“三因九毒”说

原发性肝癌致病因素的"三因九毒学说"主要包括:①内因三毒(正虚之引毒、情志之心毒、基因之天毒);②外因三毒(六淫之常毒、肝炎之疫毒、环境之癌毒);③不内外因三毒(摄生之积毒、疾病之变毒、药物之副毒)。

Accumulation and depuration of pectenotoxins in brown crab Cancer pagurus

Pectenotoxins (PTXs) are a group of marine algal toxins. In this study, the accumulation and depuration of pectenotoxins in brown crab Cancer pagurus were investigated. Crabs were fed with toxic blue mussels Mytilus edulis for 21 days and then depurated for 42 days. Toxins were extracted with methanol from the digestive glands of contaminated crabs, uncontaminated crabs (control group) and from blue mussels for comparison. Extracts were analyzed by liquid chromatograph coupled with tandem mass spectrometry (LC-MS-MS). The concentrations of PTX-2, PTX-2 SA, 7-epi-PTX-2 SA, and PTX-12 were analyzed in two batches of toxic blue mussels and the crabs. A one-compartment model was applied to describe the depuration of PTXs. The half-life of PTXs was estimated to be 6–7.5 days. After depuration for 42 days, the amount of PTXs measured in the crab digestive glands was less than 1 μg/kg.

Prolonged cholestasis after raloxifene and fenofibrate interaction: A case report

Assigning causality in drug-induced liver injury is challenging particularly when more than one drug could be responsible. We report a woman on long-term therapy with raloxifen who developed acute cholestasis shortly after starting fenofibrate. The picture evolved into chronic cholestasis. We hypothesized that an interaction at the metabolic level could have triggered the presentation of hepatotoxicity after a very short time of exposure to fenofibrate in this patient. The findings of an overexpression of vascular endothelial growth factor in the liver biopsy suggest that angiogenesis might play a role in the persistance of toxic cholestasis.

Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis

Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.

CUMULATIVE RESULTS OF CHEMOSENSITIVITY TEST USING MTT ASSAY IN DOUBLE-LAYER AGAROSE

Objective To investigate cumulative results of chemosensitivity test using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl （MTT） assay in double-layer agarose. Methods A total of 2 491 patients with different kinds of cancers were enrolled in the study, in which 18 kinds of different anticancer drugs were used. A computer soft was used to get charts. ResultsThe total evaluability rate was 82.7% （2 060/2 491）. Among all agents, the efficiency rates of 5-Fu, MMC, DDP, BLM and CBP were higher than the efficiency rates of others. The response rate range of different cancer in vitro sensitivity by using MTT assay in double layer agarose were from 9.2% （biliary duct） to 37.5% （malignant lymphoma）. For colon and rectum cancer, 5-Fu, DDP, MMC and BLM were more sensitive than other anti-tumor agents. For breast carcinomas, ACTD and DDP were more sensitive. For gastric cancer, 5-Fu, DDP and BLM were more sensitive. For leukemia, VM-26 and HHRT were more sensitive. ACM was more sensitive to kidney and MXT and BLM were more sensitive to pancreas cancer. For Lung cancer, DDP and EPI were more sensitive. Mean true positive rate, mean true negative rate, mean sensitivity, mean specificity and mean accuracy were 44% , 92% , 72% , 77% , and 76% , respectively. Conclusion Chemosensitivity tesing using the MTT assay in a double layer agarose was a very useful reference to chem- therapy.

Phyto-Toxicity of Chromium in Maize： Oxidative Damage, Osmolyte Accumulation, Anti-Oxidative Defense and Chromium Uptake

Agricultural production systems are immensely exposed to different environmental stresses in which heavy metal stress receives serious concerns. This study was conducted to explore the deleterious effects of different chromium （Cr） stress levels, i.e., O, 30, 60, 90, 120, and 150 μmol L^-1, on two maize genotypes, Wandan 13 and Runnong 35. Both genotypes were evaluated by measuring their growth and yield characteristics, Cr accumulation in different plant tissues, alterations in osmolyte accumulation, generation of reactive oxygen species （ROS）, and anti-oxidative enzyme activity to scavenge ROS. The results showed that Cr stress decreased the leaf area, cob formation, 100-grain weight, shoot fresh biomass, and yield formation, while Cr accumulation in different maize tissues was found in the order of roots 〉 leaves 〉 stem ~ seeds in both genotypes. The increased Cr toxicity resulted in higher free proline, soluble sugars and total phenolic contents, and lower soluble protein contents. However, enhanced lipid peroxidation was noticed in the forms of malondialdehyde, hydrogen peroxide （H2O2） and thiobarbituric acid reactive substance accumulation, and electrolyte leakage. The hyperactivity of superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, especially glutathione peroxidase and glutathione reductase indicated that these anti-oxidative enzymes had a central role in protecting maize from Cr toxicity, especially for Wandan 13. Moreover, higher uptake and less translocation of Cr contents into the grains of Wandan 13 implied its importance as a potential candidate against soil Cr pollution.

Citric Acid-Enhanced Electroremediation of Toxic Metal-Contaminated Dredged Sediments： Effect of Open/Closed Orifice Condition, Electric Potential and Surfactant

Citric acid(CA), a widely used eco-friendly electrolyte, can be employed as an agent for enhancing toxic metal(TM) removal from contaminated dredged sediment using electrokinetic(EK) technology. In this study, dredged harbor sediments co-contaminated by TMs were subjected to enhanced EK treatment using a mixture of chelating agent(CA) and surfactant as an additive in the processing fluids. Several control conditions that may influence the efficiency of TM removal were tested, including open/closed sediment chamber orifices, electric potential gradients(0.5, 1.0, and 1.5 V cm^(-1)), and electrolyte surfactant. Tween 20(4 mmol L-1) was used as a surfactant within the electrolyte to investigate the extent of TM removal in sediment with high organic matter content. The results showed that an open orifice led to a greater electro-osmotic flow(EOF) with moderate TM removal. In contrast, a closed orifice with a nonionic surfactant electrolyte allowed the highest removal of TMs from the matrix. Moreover, increasing the electric potential gradient led to a higher EOF under the open orifice condition, but no significant increase in TM removal was observed owing to a higher accumulation of TMs in the middle of the matrix, caused by the opposite direction of EOF and electro-migration of metal-citrate complexes.

Graph attention convolutional neural network model for chemical poisoning of honey bees’ prediction

The impact of pesticides on insect pollinators has caused worldwide concern. Both global bee decline and stopping the use of pesticides may have serious consequences for food security. Automated and accurate prediction of chemical poisoning of honey bees is a challenging task owing to a lack of understanding of chemical toxicity and introspection. Deep learning(DL) shows potential utility for general and highly variable tasks across fields. Here, we developed a new DL model of deep graph attention convolutional neural networks(GACNN) with the combination of undirected graph(UG) and attention convolutional neural networks(ACNN) to accurately classify chemical poisoning of honey bees. We used a training dataset of 720 pesticides and an external validation dataset of 90 pesticides, which is one order of magnitude larger than the previous datasets. We tested its performance in two ways: poisonous versus nonpoisonous and GACNN versus other frequently-used machine learning models. The first case represents the accuracy in identifying bee poisonous chemicals. The second represents performance advantages. The GACNN achieved ~6% higher performance for predicting toxic samples and more stable with ~7%Matthews Correlation Coefficient(MCC) higher compared to all tested models, demonstrating GACNN is capable of accurately classifying chemicals and has considerable potential in practical applications.In addition, we also summarized and evaluated the mechanisms underlying the response of honey bees to chemical exposure based on the mapping of molecular similarity. Moreover, our cloud platform(http://beetox.cn) of this model provides low-cost universal access to information, which could vitally enhance environmental risk assessment.