The preclinical safety assessment of hepatotoxicity drugs has a low sensitivity and low specificity. Related tests often generate false negative results and unexpected toxicity,which is one of the major reasons for the cessation of development and withdrawal from the market. Proteomics enjoys advantages of rapidness,high sensitivity and high throughout,and therefore can be used in the search for new biomarkers of hepatotoxicity in preclinical studies,leading to the development of safer drugs and a more efficient drug discovery process. In this review,the current preclinical biomark?ers of liver toxicity and development of proteomic technologies in the discovery and validation of bio?markers of drug-induced liver injury are described,in general the application of proteomics to Chinese medicine-induced liver toxicity in particular. Compared with traditional methods,proteomic technologies show promising results for the discovery of novel hepatotoxic markers. Proteomics,in conjugation with other omics techniques,will play a major role in the early stage of hepatotoxicity screening and will prove to be a good bridge in clinics in the future.

AIM To observe the relationship between dose effect and time effect on hepatoxicity of Gardenia jasminoides Ellis extract in rats.MOTHODS Wistar rats were divided into four groups:low,middle and high (3,10,and 30 g/kg) dose of G.Jasminoides groups (administrated by gavage),and the normal control group were orally given deionized water.All rats were observed daily during the administration period.On the 7th,14th,28th day after the administration,blood samples were collected;serum alanine transaminase (ALT),aspartate transaminase (AST),alkaline phosphatase (ALP),glutamic dehydrogenase (GLDH) activity and total bile acid (TBA) and total bilirubin (TBIL) were determined.The livers were weighed and the liver index was calculated.HE staining and observation of histopathological changes in the structure of liver tissue under light microscopy were performed.RESULTS After the 7th day of administration,the rats in high dose group showed lower food consumption and slowly increased body weight.Serum ALT,AST,ALP,TBA,TBIL and GLDH in rats from high dose group were significantly higher than those in the normal control group.The liver index of rats in the middle and high dose groups was significantly increased than that in the normal control group.After the 14th day of administration,serum ALT,TBA and TBIL in rats from the high dose group were significantly higher than those in the normal group.The liver index of rats in the middle and high dose groups was significantly increased than that in the normal control group.After 28th day of administration,serum ALT and TBA in the rats from the high dose group,TBIL and GLDH in rats from the middle dose group,and GLDH in rats from the low dose group were significantly higher than those in the normal control group.The liver indexes of rats in all dose groups were significantly increased than those in the normal control group.After the 7th,14th or 28th day of the treatment,histopathological changes such as the liver cell hypertrophy,interlobular bile duct hyperplasia,and inflammatory cell infiltration appeared in the middle and high dose groups.CONCLUSION The high dose of G.jasminoides can induce and increase liver toxicity with the increase in dose,but at high dose level,liver toxicity does not increase with time.

Background Dry eye is a common disease worldwide.Cyclosporine A(CsA) is provided to be a immunosuppressive agent and is effective on dry eye.But in China,0.05％ CsA is not yet applied in dry eye treatment.Objective This study was to evaluate the efficacy and safety of 0.05％ CsA eye drops in the treatment of dry eye.Methods This was a randomized,double-blind,vehicle-controlled parallel group study.Forty eyes of 40 patients with moderate to severe dry eye were randomly divided into two groups,with the corresponding treatment of 0.05％ CsA eye drops or the vehicle emulsion.The patients in both the groups received non-preserved artificial tear.Symptoms and signs were observed before administration,(7±1),(28±2),(56±3),and (84±3) days and also 14 days after withdrawal.The clinical effective rate was considered as the primary outcome.The subjective assessment of the patients including total symptom scores and ocular surface disease index (OSDI) scores,Schirmer Ⅰ test (S Ⅰ t) with topical anaesthesia,tear film breakup time (BUT),rose Bengal and fluorescein staining scores were evaluated.The safety profile was evaluated by adverse events,visual acuity and ocular tolerance.Results At the end of this trial,the ocular symptoms scores,conjunctival hyperemia,BUT,S Ⅰ t and keratoconjunctiva staining scores of the two groups had statistically significant difference.The total effective rate of 0.05％ CsA treatment group was 75％ (15/20) and vehicle group was 25％ (5/20).There was a statistically significant difference between groups (P =0.000),and the 95％ confidence interval (C1) of the difference value of total effectiveness between the two groups was 30.80％-53.75％.At the end of this trial,there was no statistically significant difference in visual acuity distribution (P =0.890).No obvious discomfort was found in the patients received 0.05％ CsA eye drops.There were no adverse events during the follow-up duration.Conclusions 0.05％ CsA ophthalmic emulsion is an effective and safe treatment for dry eyes.

Objective To evaluate the value of L-(methyl-11C)-labeled methionine positron emissions tomography (MET PET) and MRI in target volume delineation for postoperative radiotherapy for brain high grade glioma (HGG).Methods Thirty-seven patients with supratentorial HGG were included.Both MRI and MET PET scan were performed in the same treatment position for all patients.The consistency to determine residual tumor between MRI and MET PET was analyzed.Imaging data of MET PET and MRI were coregistered using the BrainLAB image fusion software.The extension of the volume with high uptake (VMET) on MET PET were compared quantitately with the enhancing area on MRI T1W gadolinium enhancement (VGd) and the hyperintensity area on MRI T2W (VT2).Results Both MET PET and MRI were positive for 19 patients and negative for 7 patients.The consistency between these two scans was 70.3%.MET PET was integrated with MRI in 30 patients with positive MET uptake.VMET were partially or entirely outside VGd in 29 patients and VT2 in 17 patients, whereas VGd and VT2 were partially or entirely outside VMET in all patients.The maximal distance from the margin of VMET to VGd was ≥ 2.0 cm in 50%patients and the corresponding distance of VMET to VT2 was ≥ 1.0 cm in 33% patients.Conclusions The differences are existing between MET PET and MRI in determination and identification of the location and extension of residual tumor for patients with HGG.The integration of MET PET and MRI can accurately delineate radiation target volume.

[ABSTRACT]AIM:ToinvestigatetherolesofthecanonicalWntpathwayinautism.METHODS:Usinganau-tistic model induced by prenatal exposure to valproic acid ( VPA) , we detected the expression of the signaling molecules of the canonical Wnt pathway in the prefrontal cortex (PFC) and hippocampus formation (HF) of autistic rats.The expres-sion levels of glycogen synthase kinase 3β( GSK-3β) , phosphorylated GSK-3β, β-catenin and phosphorylated β-catenin were observed by Western blotting .The mRNA expression of GSK-3β, β-catenin, c-Myc and cyclin D1 was assessed by semi-quantitative RT-PCR.RESULTS:The results of Western blotting showed that inactivated GSK-3β(Ser9) phospho-rylation was significantly increased , and inhibitory β-catenin ( Ser33/37/Thr41 ) phosphorylation was obviously decreased compared with control group .The results of RT-PCR showed that the mRNA levels of β-catenin, c-Myc and cyclin D1 in-creased, and GSK-3βwas significantly enhanced in VPA-exposed rats compared with the controls .CONCLUSION: In-creased activity of canonical Wnt pathway in the PFC and HF of autistic rats may contribute to the susceptibility to autism .

Objective To investigate the relationship between the composition of vaginal microbiota and the course of cervical precancerous lesion.Methods A total of 64 vaginal swabs were collected from 22 healthy women, 18 CINⅠ patients and 24 CINⅡ/Ⅲ patients who visited Obstetrics and Gynecology of the Second Xiangya Hospital of Central South University during July 2014 and July 2015.The Bacterial genomic DNA was extracted and the V3 and V4 hypervariable regions of 16S rRNA were amplified and high-throughput sequenced.The abundance and composition of vaginal microbiota were analyzed by Uparse, Mothur and LefSe statistical software.Results There was no significant difference in Alpha diversity index between CINⅡ/Ⅲ group(Chao:63±32;ACE:72±38;Simpson:0.70±0.27;Shannon:0.70±0.63) and control group ( Chao:48±24;ACE:54±25;Simpson:0.71±0.27;Shannon:0.65±0.58)(W=192,P=0.11;W=189,P=0.10;W=281,P=0.72;W=241,P=0.62).The ACE(85±37) and Chao(66±25) values of CINⅠgroup were significantly different from those of the control group (ACE:54±25;Chao:48±24)(W=99,P=0.006;W=113,P=0.02).At the phylum level, 78.69%(309 020/392 722) of the vaginal microbiota in the control group was Firmicutes, 16%(62 846/392 722) was Actinobacteria.Firmicutes was reduced to 64.86%(208 422/321 318) and Actinobacteria increased to 27.71%(89 040/321 318) in CINⅠgroup.The composition of vaginal microbiotain in CINⅡ/Ⅲ group was similar to those of control group.At the genus level, the composition of vaginal microbiota were similar between CINⅡ/Ⅲ group and control group, with Lactobacillus as predominant genus[71.81%(307 658/418 424)], Gardnerella[12.91%(55 299/428 424)], others such as Prevotella, atopobium were less.In the CINⅠ group, the abundance of Lactobacillus was decreased to 56.26%(180 787/321 318), Gardnerella was increased to 19.62%(63 057/321 318), and Listeria was increased to 7.7%(24 746/321 318).The composition of vaginal microbiota in the most samples was classified as CSTⅢ and CSTⅠ, with Lactobacillus inersand and Lactobacillus crispatus were dominant respectively.There was no significant difference in the composition of vaginal microbiota between the three groups(χ2=2.72, P=0.949).LEfSe analysis showed that the abundance of bacteria in CIN group and control group were varied.At the genus level, there were significant differences in the abundance of Geobacter, Atopobium and Ureaplasma (P<0.05, P<0.05, P<0.01, respectively).At the species level, there was significant difference in the abundance of Ureaplasma urealyticum serotype 9 (P<0.01).Conclusion The diversity and the composition of vaginal microbiota were similar between CIN patients and healthy women, but the abundances of some bacteria were varied, with Ureaplasma increased in patients with CIN.

Objective To evaluate the advantage of 3D printing technique in treatment of complicated ace-tabula fracture,we compared the early clinical outcomes of surgical treatment for complex acetabula fracture with traditional surgery(group A)and that assisted by 3D printing technique(group B).Methods A prospective anal-ysis of 35 complicated acetabula fractures was performed at our department,13 patients cured assisted with 3D printing technique. The other 22 patients performed traditional surgery. Surgical trauma,systematic inflammation, immediate reduction effect were evaluated by Matta image assessment standard,and rehabilitation functional status evaluated by Harris score system and Merled' Aubigne and Postel Grading standard. Results There were signifi-cant differences between the two groups regarding intraoperative blood loss,postoperative drainage,operation time (P<0.05),and group B was superior to group A.C reactive protein,leucocyte and creatine kinase MM in periph-eral blood in group A were much higher than those in group B at 24 hours postoperatively(P<0.01).The result of reduction of fracture is poor in group A,but excellent rate of reduction is about 84% in group B. The result of Merled' Aubigne and Postel scores grading was superior in group B(P = 0.013). The excellent and good rate of Harris function score in B group was significantly higher than that in group A(P=0.027).Conclusion The treat-ment of complicated acetabula fracture assisted by 3D printing is excellent in short-term follow up,achieving good reduction with limited trauma,long-term prognosis needs to be further followed up.

Objective:Tumor-treating fields (TTFields) is a kind of non-invasive anti-mitotic tumor therapy, which has been approved for patients with newly diagnosed and recurrent glioblastoma. This study aims to explore the efficacy and safety of TTFields in high-grade gliomas in clinical practice settings.Methods:The clinical data of 15 patients with recurrent glioma and 9 patients with newly diagnosed high-grade glioma admitted to our center from April 2019 to January 2021 were retrospectively analyzed. All patients accepted TTFields≥1 month. Follow-up was performed for 5.3 months (ranged from 2.3 to 10.7 months); Response Assessment in Neuro-Oncology Working Group (RANO) criteria was used to evaluate the glioma responses. The progression-free survival (PFS) and overall survival (OS) were calculated according to Kaplan-Meier method. Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Quality of life questionnaire-core 30 (QLQ-C30) and QLQ-brain cancer module (QLQ-BN20) questionnaires were used to evaluate the health-related quality of life (HRQoL). Treatment compliance was evaluated by data on the use of NovoTTF-200A devices, and calculated as a percentage of daily TTFields usage.Results:The median duration of TTFields was 4.2 months (ranged from 1.0 to 10.7 months), with a median compliance rate of 91.5% (67.0%-97.0%). TTFields was used alone in 2 patients and used with combination of chemotherapy in 22 patients. From follow-up to April 2021, 14 patients had stable symptoms and 10 had disease progression (8 died). The median PFS and OS of recurrent patients were 5.9 months ( 95%CI: 3.3-8.6 months) and 8.5 months ( 95%CI: 3.2-13.8 months), respectively; and the median PFS and OS of newly diagnosed patients were both 10.7 months (without 95%CI). The common adverse events included grading 1 dAE (58.3%) and grading 2 dAE (12.5%), without grading 3 or 4 dAE, manifested as contact or allergic dermatitis, erosion, folliculitis and ulcers. And 87.5% patients had stable HRQoL. Conclusions:The preliminary results showed that the survival of recurrent high-grade glioma patients treated by TTFields is similar to that reported in foreign literature; and the newly diagnosed patients need further survival follow-up. The patients' treatment compliance and safety are good. The dAE incidence (grading 1-2) is higher than that reported in the literature, and the toxicity was acceptable.

【Objective】 To explore the correlation between serological screening of human T-lymphotropic virus antibodies (anti HTLV) and Western blot(WB) confirmatory tests among blood donors, so as to explore the infection status of HTLV Ⅰ/Ⅱ in Guangzhou. 【Methods】 The anti HTLV Ⅰ/Ⅱ enzyme-linked immunosorbent assay(ELISA) kit was used to screen voluntary blood donors from Guangzhou Blood Center from July 2016 to August 2022. WB was used to confirm 395 reactive blood samples by ELISA. The correlation between the S/CO values of anti HTLV Ⅰ/Ⅱ ELISA reagents and the confirmatory test was analyzed using ROC curves. 【Results】 The results showed that 25 out of 395 initially screened reactive blood donor samples were confirmed as HTLV positive by WB, while 16 were uncertain. ROC curve analysis showed a correlation between the S/CO values by ELISA and the confirmatory test results: the S/CO value at the highest Youden index was 3.789, which was the optimal threshold. The S/CO value had a certain correlation with the predicted positive rate of confirmatory results (P<0.05): the larger the S/CO value, the higher the predicted positive value. The overall prevalence of HTLV in Guangzhou is relatively low. 【Conclusion】 The prevalence of HTLV among blood donors in Guangzhou is low.Since the false positive rate of HTLV Ⅰ/Ⅱ antibody by ELISA serological screening is high, the confirmatory testing is particularly important.

Objective To investigate the consistency between Shengxiang (S) and Xinbo (X) real-time PCR methods in the quantification of HBV RNA. Methods In the prospective follow-up cohort of 108 chronic hepatitis B (CHB) patients established from July 2007 to August 2008, 20 patients with HBeAg seroconversion were selected, and 20 patients without seroconversion were selected by propensity score matching at a ratio of 1∶ 1. The two quantification methods from S and X companies were used, and a retrospective analysis was performed for HBV RNA in serum samples at baseline and weeks 12, 24, and 48. The paired t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data. The Pearson correlation coefficient, intraclass correlation coefficient (ICC), and the Bland-Altman method were used to evaluate the consistency of the two quantification methods. Results A total of 132 serum samples were tested by S reagent, and 154 were tested by X reagent; the detection rate of HBV RNA was 100% by both reagents. A total of 131 serum samples were tested by both reagents, with 34 samples at baseline and 29, 35, and 33 samples, respectively, at weeks 12, 24, and 48 of follow-up; at these four time points, the HBV RNA quantification data detected by X reagent were significantly higher than those detected by S reagent (5.75±1.64/5.43±1.73/5.13±1.54/4.76±1.55 log 10 copies/mL vs 4.80±1.48/4.52±1.53/4.10±1.50/3.92± 1.43 log 10 copies/mL, t =8.348, t =5.341, Z =-5.086, Z =-4.762, all P < 0.001). The correlation analysis of the two methods showed a Pearson correlation coefficient of 0.915 (95% confidence interval [ CI ]: 0.836-0.957) and an ICC of 0.771(95% CI : -0.021 to 0.931) at baseline, a Pearson correlation coefficient of 0.849(95% CI : 0.701-0.927) and an ICC of 0.733(95% CI : 0.138-0.902) at week 12, a Pearson correlation coefficient of 0.951(95% CI : 0.905-0.975) and an ICC of 0.776(95% CI : -0.058 to 0.942) at week 24, and a Pearson correlation coefficient of 0.933(95% CI : 0.867-0.967) and an ICC of 0.804(95% CI : -0.014 to 0.944) at week 48 (all P < 0.05). The Bland-Altman analysis showed that the difference of 96.18%(126/131) samples tested by the two methods was within the mean difference±1.96 standard deviation. Conclusion HBV RNA quantification by X reagent is higher than that by S reagent, while the two real-time PCR quantification methods show a good consistency in CHB patients with HBeAg seroconversion and those without seroconversion.