Objective To observe the effects of applying incremental positive end expiratory pressure(PEEP)lung recruitment method in lung protective ventilation strategy during anesthesia for laparoscopic colorectal cancer surgery on the respiratory mechanics and postoperative pulmonary complications.Methods The patients who underwent laparoscopic colorectal cancer surgery from June to December 2023 were randomly divided into two groups with 30 cases each group:the incremental PEEP lung recruitment combined with lung protective ventilation method group(RM group)and the lung protective ventilation method group(control group,C group).Both groups underwent lung protective ventilation.The RM group underwent the first lung recruitment immediately after the placement of Trendlenburg position,and then the lung recruitment was performed with the incremental PEEP method hourly thereafter.In the C group,no lung recruitment was performed throughout the procedure.The data of respiratory mechanics and oxygenation were recorded at 5 min before tracheal intubation(T0),immediately after tracheal intubation(T1),after the first pulmonary recruitment(after positioning in the C group)(T2),after the second pulmonary recruitment(60 min after positioning in the C group)(T3),after stopping the pneumoperitoneum(T4),and 30 min after extubation(T5),respectively.Postoperative pulmonary complications(PCC)were compared between the two groups.Results In terms of respiratory mechanics:the differences in peak airway pressure(Ppeak),airway plateau pressure(Pplat),driving pressure(△P),and pulmonary dynamic compliance(Cdyn)at the time point of T1 between the two groups were not significant(P＞0.05);the Ppeak,Pplat,and △P at the time points of T2 and T3 in the RM group were smaller than those in the C group(P＜0.05),and the Cdyn was larger than that in the C group(P＜0.05);the Ppeak at the time point of T4 in the RM group was smaller than that in the C group(P＜0.05),while the Pplat,△P,and Cdyn were not significant(P＞0.05).In terms of oxygenation:the differences in arterial partial pressure of oxygen(PaO2)and partial pressure of CO2(PaCO2)at the time point of T0 in the two groups were not significant(P＞0.05);the PaO2 at the time points of T3,T4,and T5 in the RM group was higher than that in the C group(P＜0.05),and the PaCO2 at the time points of T4 and T5 was lower than that in the C group(P＜0.05).In terms of postoperative pulmonary complications,the incidences of pulmonary atelectasis(5 cases vs.12 cases,P=0.045)and PPC(9 cases vs.18 cases,P=0.020)were lower in the RM group than those in the C group,while the difference of incidence of pulmonary infection and pleural effusion between the two groups was not significant(P＞0.05).There was no occurrence of respiratory failure in both groups.Conclusion Application of incremental PEEP lung recruitment in lung protective ventilation strategy can improve lung respiratory mechanics and reduce incidence of postoperative pulmonary complications in patients undergoing laparoscopic colorectal cancer surgery.

Micro/nanoplastics (MNPs), recognized as emerging environmental pollutants, are widely distributed in natural environments. Due to their small particle size and significant migratory capacity, MNPs can infiltrate diverse environmental matrices, then invade and accumulate in the organism via the skin, respiration, and digestion. Recently, concerns have grown over the detrimental effects and potential toxicity of MNPs on reproductive health. This review summarized published epidemiological and toxicological studies related to MNPs exposure and their effects on reproductive health. Firstly, this review critically examined the current landscape of epidemiological evidence and found that MNPs (e.g., polystyrene, polypropylene, polyvinyl chloride, polyethylene, etc.) are present in various biological specimens from both males and females, and their presence may be associated with an increased risk of reproductive disorders. Secondly, extensive toxicological studies revealed that MNPs exposure induces reproductive health damage through mechanisms such as disrupting the microstructure of reproductive organs and altering molecular-level expressions. Oxidative stress, inflammatory responses, and apoptosis are identified as potential links between MNPs exposure and reproductive damage. Finally, this review addressed the prevalent shortcomings in existing studies and proposed future directions to tackle the challenges posed by MNPs-induced reproductive harm. These insights aim to inform strategies for safeguarding public reproductive health and ecological security, providing a scientific foundation for mitigating risks associated with MNPs pollution.

Objective To observe the effects of applying incremental positive end expiratory pressure(PEEP)lung recruitment method in lung protective ventilation strategy during anesthesia for laparoscopic colorectal cancer surgery on the respiratory mechanics and postoperative pulmonary complications.Methods The patients who underwent laparoscopic colorectal cancer surgery from June to December 2023 were randomly divided into two groups with 30 cases each group:the incremental PEEP lung recruitment combined with lung protective ventilation method group(RM group)and the lung protective ventilation method group(control group,C group).Both groups underwent lung protective ventilation.The RM group underwent the first lung recruitment immediately after the placement of Trendlenburg position,and then the lung recruitment was performed with the incremental PEEP method hourly thereafter.In the C group,no lung recruitment was performed throughout the procedure.The data of respiratory mechanics and oxygenation were recorded at 5 min before tracheal intubation(T0),immediately after tracheal intubation(T1),after the first pulmonary recruitment(after positioning in the C group)(T2),after the second pulmonary recruitment(60 min after positioning in the C group)(T3),after stopping the pneumoperitoneum(T4),and 30 min after extubation(T5),respectively.Postoperative pulmonary complications(PCC)were compared between the two groups.Results In terms of respiratory mechanics:the differences in peak airway pressure(Ppeak),airway plateau pressure(Pplat),driving pressure(△P),and pulmonary dynamic compliance(Cdyn)at the time point of T1 between the two groups were not significant(P＞0.05);the Ppeak,Pplat,and △P at the time points of T2 and T3 in the RM group were smaller than those in the C group(P＜0.05),and the Cdyn was larger than that in the C group(P＜0.05);the Ppeak at the time point of T4 in the RM group was smaller than that in the C group(P＜0.05),while the Pplat,△P,and Cdyn were not significant(P＞0.05).In terms of oxygenation:the differences in arterial partial pressure of oxygen(PaO2)and partial pressure of CO2(PaCO2)at the time point of T0 in the two groups were not significant(P＞0.05);the PaO2 at the time points of T3,T4,and T5 in the RM group was higher than that in the C group(P＜0.05),and the PaCO2 at the time points of T4 and T5 was lower than that in the C group(P＜0.05).In terms of postoperative pulmonary complications,the incidences of pulmonary atelectasis(5 cases vs.12 cases,P=0.045)and PPC(9 cases vs.18 cases,P=0.020)were lower in the RM group than those in the C group,while the difference of incidence of pulmonary infection and pleural effusion between the two groups was not significant(P＞0.05).There was no occurrence of respiratory failure in both groups.Conclusion Application of incremental PEEP lung recruitment in lung protective ventilation strategy can improve lung respiratory mechanics and reduce incidence of postoperative pulmonary complications in patients undergoing laparoscopic colorectal cancer surgery.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

【Objective】 To evaluate the effectiveness of Roche Cobas s 201 in detecting HBV by analyzing its blood nucleic acid testing (NAT) results. 【Methods】 The results were grouped according to the enzyme-linked immunosorbent assay (ELISA) and NAT minipool test (MP), NAT individual test (ID) and repeated NAT ID test (rID), and categorized into 4 groups as ELISA+ /NAT(ID)+ , ELISA+ /NAT(rID)+ , ELISA-/NAT(ID)+ and ELISA-/NAT(rID)+ . The data were statistically analyzed to explore whether there was a difference in the detection of reactive results by repeated NAT, and the correlation between cycle threshold (Ct) and nucleic acid detection rate for NAT-reactive samples with different ELISA results. The true infection status of blood donors was further analyzed by supplementary tests, including NAT systems and chemiluminescence serological marker assays using other methodologies. 【Results】 A total of 1 691 groups of 766 293 blood donor samples were HBV NAT(MP)+ , of which 1 418 groups(83.86%) were detected with reactive results (1 418 HBV NAT+ , 7 090 NAT-), and there were still 273 groups (16.14%) that remained undetected after repeated testing[a total of 1 638 NAT-, Ct(MP): 39.49±3.62]. Of the HBV NAT+ , 881(62.13%) were ELISA+ /NAT(ID)+ , 19(1.34%) were ELISA+ /NAT(rID)+ , 451(31.81%) were ELISA-/NAT(ID)+ , and 67(4.72%) were ELISA-/NAT(rID)+ . For samples with different ELISA results, difference was found in the detection of HBV by repeated NAT (P<0.05). There was no difference in Ct(ID) values between groups ELISA+ /NAT(rID)+ and ELISA-/ NAT(ID)+ , and groups ELISA+ /NAT(rID)+ and ELISA-/ NAT(rID)+ (P>0.05), but there were significant differences between other groups compared pairwise (P<0.05). Supplementary tests were performed on 228 ELISA-/ NAT(MP)+ (ID)- samples, 56 (24.56%) were reactive by chemiluminescent detection of HBsAg+ and 7 (3.07%) by other NAT systems. Among the remaining 221 NAT- samples/donors (96.93%), 53 (23.98%) HBsAg+ donors were likely to have chronic infection, 40 (18.10%) anti-HBe+ and/or anti-HBc+ donors might have previous infections, and the remaining 128 (57.92%) donors who were non-reactive were NAT (MP) pseudo-reactive, with significant differences in anti-HBs levels \'between groups (P<0.05). 【Conclusion】 Repeated NAT has differential detection of donor samples with different reactivity categories or different serologic results, especially within a certain interval, and repeated NAT for ELISA- samples can significantly improve the detection rate. Ct values can assist in assessing the stability and accuracy of the NAT system. For ELISA-/NAT(MP)+ (ID)- donors, the combination of other highly sensitive assays can reduce the risk of viral residuals and safeguard clinical blood safety.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To provide more objective reference in diagnosis and prognosis of coronary heart disease(CHD)combined with heart failure(HF)by analyzing features of pulse graph parameters improved with moving average line method of patients with CHD combined with HF.Methods From September 2018 to December 2020,a random sampling method was used to collect 78 inpatients with CHD and 73 inpatients with CHD combined with HF in department of cardiology of Shu Guang Hospital Attached to Shanghai TCM University,Shanghai Municipal Hospital of Traditional Chinese Medicine and Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine as well as 78 healthy people from physical examination center of Shu Guang Hospital Attached to Shanghai TCM University and Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine.Smart TCM-I type pulse digital acquisition analyzer was used to collect pulse samples.χ2 test,LSD test,Dunnett's T3 test and Kruskal Wallis test were used to analyze the differences of pulse graph parameters among the groups improved with moving average line method.Results ①Results of pulse graph parameters about chronaxy:Compared with those in healthy people,t5 of patients with CHD decreased significantly(P<0.01),t,t3,t5 of patients with CHD combined with HF increased significantly(P<0.01).Compared with those in patients with CHD,t5 of patients with CHD combined with HF increased significantly(P<0.01),t3 increased(P<0.05).②Results of pulse graph parameters about ratio of chronaxy:Compared with those in healthy people,t1/t,w/t,tf/4/t,tf/3/t4,tf/4/t4,tf/5/t4,tf/3/tmax,tf/4/tmax,tf/5/tmax,tf/6/tmax of patients with CHD decreased significantly(P<0.01),tmax/t,w/t4,tf/3/t,tf/5/t,tf/6/t,tf/6/t4 decreased(P<0.05),t0.8/tmax increased(P<0.05),w/t,t0.9/t,t0.8/t,tf/3/t,tf/4/t,tf/5/t,tf/6/t,tf/3/t4,tf/4/t4,tf/3/tmax,tf/4/tmax,tf/5/tmax,tf/6/tmax of patients with CHD combined with HF decreased significantly(P<0.01),t1/t,tmax/t,w/t4,t0.9/t4 decreased(P<0.05),t3/t4 increased significantly(P<0.01).Compared with those in patients with CHD,t0.9/tmax of patients with CHD combined with HF decreased significantly(P<0.01),t0.9/t,t0.8/tmax decreased(P<0.05),t3/t4 increased significantly(P<0.01).③Results of pulse graph parameters about amplitude:Compared with those in healthy people,h4 of patients with CHD decreased(P<0.05),h3,h4 of patients with CHD combined with HF decreased significantly(P<0.01).Compared with those in patients with CHD,h5 of patients with CHD combined with HF decreased significantly(P<0.01),h3 decreased(P<0.05).④Results of pulse graph parameters about ratio of amplitude:Compared with those in healthy people,h4/h1 of patients with CHD decreased(P<0.05),h3/h1,h4/h1 of patients with CHD combined with HF decreased significantly(P<0.01).Compared with those in patients with CHD,h5/h1 of patients with CHD combined with HF decreased significantly(P<0.01).Conclusion Patients with CHD combined with HF characterize a weakening arterial compliance and an increasing peripheral resistance.Their cardiac contractility is decreased with shorten rapid ejection phase.The myocardium is likely to remodel which leads to a slower heart rate and the decreased stroke volume may cause a low pulse pressure.Patients with CHD combined with HF are more likely to suffer from decreased function of aortic valve.The most common pulse conditions are infrequent pulse,uneven pulse,thready pulse,slippery pulse and taut pulse.Pulse graph parameters improved with moving average line method can provide more objective reference in studying features of pulse graph of CHD combined with HF.It is conducive to further promote the objectification of pulse diagnosis.

Objective:Analysis of hepatitis B surface antigen negative donations, initial detection of reactivity followed by subsequent differential tests or repeat the infection status of non-discriminated reactive (NDR) unresponsive blood donors to explore whether different nucleic acid detection systems have differences in the detection of HBsAg -/NDR. Methods:The test result and reactivity rates of blood donor samples received from January 2020 to August 2022 were compared, and some samples were repeated for both nucleic acid testing systems, and the characteristics of the HBsAg -/HBV DNA + blood donors were analyzed. Results:Through the analysis of nucleic acid result from January 2020 to August 2022, repeated nucleic acid detection can improve the detection of HBsAg -/NDR blood donors, and the detection rate is offset in different cycle threshold valve ( Ct value) intervals or different sample absorbance to cut-off absorbance ratio ( S/ CO value) interval. Also grouping of Ct values or S/ CO values revealed that there was variability in detection rates between intervals in the two nucleic acid detection systems (PCR: X2=108.23, P<0.001, TMA: X2=40.95, P<0.001), mainly concentrated in Ct values less than 38.5 or S/ CO values between 10 and 15. And analysis of selected HBsAg -/HBV DNA + blood donor populations revealed that repeat nucleic acid testing was found for donors of different age ( X2=9.38, P=0.025), number of blood donations ( X2=22.52, P<0.001), occupation ( X2=24.92, P=0.002) and education level ( X2=10.37, P=0.016) significant differences, while there was no statistically significant difference for blood donors by gender ( X2=9.38, P>0.05), with far more males (67.50%) than females. Conclusions:For blood donors with a Ct value of less than 38.5, or an S/ CO value between 10 and 15, or a blood donor at the age of 41 to 50 years, another detection technology can be combined to improve the detection rate, reduce the potential risk of virus transmission of HBsAg -/NDR blood donors, and ensure the safety of clinical blood.

Objective:To analyze the situation of hepatitis B enzyme immunoassay-positive but nucleic acid negative infection (HBsAg ELISA(+ )/HBV-DNA(-)) among unpaid blood donors in Zhejiang Blood Center, and to explore the causes of inconsistency between enzyme immunoassay and nucleic acid result.Methods:A single nucleic acid test was performed on blood donors whose routine blood screening result were HBsAg-ELISA(+ )/HBV-DNA(-), and the test result of such blood donors were analyzed.Results:A total of 205 HBsAg-ELISA(+ )/HBV-DNA(-) samples were screened from 114017 blood donors from May to November, 2022. The proportion of male blood donors (0.14%) were significantly lower than that of the female blood donors (0.24%)( χ2= 14.761, P<0.005); the proportion of the first blood donor (0.32%) was significantly higher than that of the second blood donor (0.09%) ( χ2 = 78.781, P<0.005); the difference between different education levels is statistically significant ( χ2 =47.753, P<0.005). After single-person nucleic acid re-detection, the re-detection rate of nucleic acid in ELISA double-reagent positive samples was higher than that in single-reagent positive samples ( χ2=94.378, P<0.005); there was no significant difference between ELISA reagent 1 and reagent 2 in the detection rate of nucleic acid ( χ2 =0.163, P>0.005). There was no significant difference in the positive rate of secondary nucleic acid detection between the two nucleic acid detection systems ( χ2=0.626, P>0.005). Serological supplementary test showed that 11 HBV-DNA(+ ) samples showed two serological combination patterns after chemiluminescence detection, namely HBsAg(+ )/HBeAb(+ ) and HBeAb(+ ), most of which were HBsAg(+ )/HBeAb (+ ), a total of 10 cases, accounting for 90.91%, and only one case was HBeAb (+ ), accounting for 9.09%. The quantitative result of HBsAg showed that most of them were at low HBsAg level. Conclusions:After re-detection by single nucleic acid detection method, HBsAg-ELISA(+ )/HBV-DNA(-) samples of blood donors do have a certain proportion of HBV-DNA(+ ), but most of the samples were still HBV-DNA (-), additional experiments on HBV serological markers and HBV-DNA are needed to determine their true infection status and clarify the reasons for the inconsistency between enzyme immunoassay and nucleic acid test result. In addition, nucleic acid and HBsAg detection reagents with high sensitivity and specificity should be selected as far as possible in blood donor screening to ensure the accuracy of result.

OBJECTIVE To study the spectru m-toxicity relationship of in vitro hepatotoxicity of aqueous extract from Euodia rutaecarpa. METHODS The aqueous extract from 16 batches of E. rutaecarpa from different habitats were prepared. The fingerprints of aqueous extract from E. rutaecarpa were established by ultra high performance liquid chromatography （UPLC） method and Similarity Evaluation System of TCM Fingerprint （2012A edition ），and common peaks were identified and the similarity was evaluated. Using normal human hepatocytes L 02 as subject ，inhibitory effect of aqueous extract from 16 batches of E. rutaecarpa to them were investigated. The spectrum-toxicity relationship of UPLC fingerprint of aqueous extract from E. rutaecarpa with the hepatotoxicity of hepatocytes L 02 was analyzed by grey relational analysis （GRA）and partial least squares regression analysis （PLSR）. The corresponding compound of the chromatographic peak with the greatest correlation with the in vitro hepatotoxicity of E. rutaecarpa were isolated ，prepared and identified. RESULTS There were 27 common peaks in UPLC fingerprints of aqueous extract from 16 batches of E. rutaecarpa ，with similarity of 0.375-0.995. Totally 9 peaks were confirmed ，i.e. neochlorogenic acid （peak 5），chlorogenic acid （peak 9），cryptochlorogenic acid （peak 10），caffeic acid （peak 12），rutin （peak 16），hyperin（peak 17），dehydroevotarine（peak 19），evotarine（peak 24），rutecarpine（peak 25）. The aqueous extract from 16 batches of E. rutaecarpa showed significant inhibitory effect on the growth of L 02 cells（P＜0.05 or P＜0.01），and the inhibitory rate ranged from 6.68％ to 67.95％. GRA showed that there were 18 common peaks with correlation degree greater than 0.8，which were peak 8＞peak 3＞peak 23＞peak 7＞peak 4＞peak 9＞peak 12＞peak 2＞peak 19＞peak 6＞ 4928381。E-mail：799247687@qq.com peak 15＞peak 5＞peak 1＞peak 17＞peak 21＞peak 26＞ peak 20＞peak 14 in descending order of correlation degree. PLSR showed that there were 14 peaks with regression coefficient＞0 and variable importance projection value ＞1，and the order of regression coefficient was peak 8＞peak 3＞peak 23＞ peak 2＞peak 7＞peak 4＞peak 12＞peak 9＞peak 19＞peak 5＞peak 17＞peak 26＞peak 10＞peak 15. Peak 8 had the greatest correlation with in vitro hepatotoxicity，and the corresponding compound of this peak was identified as 6-O-trans caffeoyl gluconic acid. CONCLUSIONS The in vitro hepatotoxicity of aqueous extract from E. rutaecarpa is the result of multiple component interaction，among which 6-O-trans caffeoyl gluconic acid shows closest relation with in vitro hepatotoxicity.