Interpretation on Consensus on drug-induced liver injury by CIOMS Working Group:liver injury attributed to herbal and dietary supplements / 中国中药杂志

With the increase in the medical level, the improvement of adverse drug reaction(ADR) monitoring systems, and the enhancement of public awareness of safe medication, drug safety incidents have been frequently reported. Drug-induced liver injury(DILI), especially liver injury attributed to herbal and dietary supplements(HDS), has globally attracted high attention, bringing great threats and severe challenges to the people for drug safety management such as clinical medication and medical supervision. Consensus on drug-induced liver injury had been published by the Council for International Organizations of Medical Sciences(CIOMS) in 2020. In this consensus, liver injury attributed to HDS was included in a special chapter for the first time. The hot topics, including the definition of HDS-induced liver injury, epidemiological history, potential risk factors, collection of related risk signals, causality assessment, risk prevention, control and management were discussed from a global perspective. Based on the previous works, some experts from China were invited by CIOMS to undertake the compilation of this chapter. Meanwhile, a new causality assessment in DILI based on the integrated evidence chain(iEC) method was widely recognized by experts in China and abroad, and was recommended by this consensus. This paper briefly introduced the main contents, background, and characteristics of the Consensus on drug-induced liver injury. Significantly, a brief interpretation was illustrated to analyze the special highlights of Chapter 8, "Liver injury attributed to HDS", so as to provide practical references for the medical staff and the researchers who worked on either Chinese or Western medicine in China.

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

San-Cao Granule () Ameliorates Hepatic Fibrosis through High Mobility Group Box-1 Protein/Smad Signaling Pathway / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the possible mechanism of San-Cao Granule (SCG, ) mediating antiliver fibrosis.</p><p><b>METHODS</b>A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid (UDCA, 60 mg/kg), SCG (3.6 g/kg) group, SCG (1.8 g/kg) group and SCG (0.9 g/kg) group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein (HMGB1), transforming growth factor β1 (TGF-β1), phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3), Smad7, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) and α-smooth muscle actin (α-SMA) were determined by western blot, immunohistochemistry and real time quantitative-reverse transcription polymerase.</p><p><b>RESULTS</b>Both SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and IVC and preventing the serum level reducing of ALB compared with the model group (all P<0.01). Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-β1, p-Smad3, TLR4, MyD88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group (all P<0.01).</p><p><b>CONCLUSION</b>SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-β1/Smad signaling pathway.</p>

Relationship Between Traditional Chinese Medicine(TCM)Constitution and TCM Syndrome in the Diagnosis and Treatment of Chronic Diseases / 中国医学科学杂志(英文版)

Chronic diseases are global threats to human health. By applying the traditional Chinese medicine (TCM) theory of body constitution to the treatment of chronic diseases, and comprehensively identifying and differentiating the syndrome, disease, and constitution, TCM can be fully used in the diagnosis and treatment of chronic diseases. In this manner, population-based and evidence-based modern medicine can organically align with the individual-focused and speculation-based TCM, with subsequent benefits for the control of chronic diseases, reducing their burden on human health.

Expression of FLi-1, h-caldesmon and collagen Ⅳ in glomus tumor: a clinicopathologic study / 临床与实验病理学杂志

Purpose To explore the expression of FLi-1,h-caldesmon and collagen Ⅳ in glomus tumor and possible relationship between different histological types and clinical-pathological characteristics.Methods Immunohistochemistry of EnVision method was used to detect the expression of FLi-1,h-caldesmon and collagen Ⅳ in 35 cases of glomus tumor under microscope,and the relationship between different histological types and clinical-pathological characteristics was analyzed.Results The pathological morphology of tumor cells was round or polygonal,patchy distribution in blood vessels or arranged in a ring around the blood vessels.The tumor cell boundary was clear and the shape was regular,gradual transition between tumor cells and spindle smooth muscle cells was sometimes visible.The positive rate of FLi-1,h-caldesmon and collagen Ⅳ in 35 cases of glomus tumor were 58.6％,97.1％ and 100％ respectively.Different histological types of glomus tumors had no correlation with the sex of patient and the size of tumor,but had correlation with the age of patient.Vimentin and SMA were positive for glomus tumors by immunohistochemistry in 35 cases.CD34 was positive in 2 cases.Desmin positive was found in 1 case.EMA,S-100,CgA,CD68 and CD99 were negative.Conclusion h-caldesmon and collagen Ⅳ are the markers for glomus tumor diagnosis,and FLi-1 can serve as a good auxiliary reference marker.

nhibitory effect and mechanism of deoxyschizandrin on NLRP3 inflammasome / 药学学报

This study was conducted to investigate the inhibitory effect and the molecular mechanism of deoxyschizandrin on the activity of NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome. Bone marrow-derived macrophages were used to study the effects of deoxyschizandrin on inflammasome activation using inflammasome inducers (ATP and nigericin). Cytotoxic effect was evaluated with CCK-8. The expression of IL-1β, caspase-1 in the supernatant and the expression of pro-caspase-1, pro-IL-1 β, ASC, NLRP3 in cell was detected by Western blot for the inhibitory effect of deoxyschizandrin (25, 50, 100 and 200 μmol·L-1) on the activity of NLRP3 inflammasome. Immunofluorescence was applied to investigate NF-κB (p65) transportation to the nucleus. The results of CCK-8 showed that the optimum concentration of deoxyschizandrin was 6.25-400 μmol·L-1. Deoxyschizandrin (25, 50, 100, and 200 μmol·L-1) could inhibit the activation of NLRP3 inflammasome caused by nigericin and ATP, and inhibit the secretion of IL-1 β, which was associated with inhibiting the cleavage of pro-caspase-1. The results of immunofluorescence and Western blot also suggest that the inhibitory activity of deoxyschizandrin on NLRP3 inflammasome was not dependent on NF-κB pathway and protein expression of NLRP3, ASC, pro-caspase-1 and pro-IL-1 β mediated by NF-κB. Our results confirmed that deoxyschizandrin could suppress the cleavage of pro-caspase-1 and inhibit the activity of NLRP3 inflammasome at 25-200 μmol·L-1 to reduce the inflammation response.

Analysis of Clinical Characteristics in 595 Patients with Herb-induced Liver Injury / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe clinical characteristics of herb-induced liver injury (HILI).</p><p><b>METHODS</b>General conditions, medical history, clinical manifestations, biochemical indices, prognosis, and Roussed Uclaf Causality Assessment Method (RUCAM) scores were retrospectively analyzed in 595 inpatients at 302 Military Hospital between January 2009 and January 2014.</p><p><b>RESULTS</b>There were 423 cases (accounting for 71.1%) were females with multiple onset age ranging 41 to 50 years old. The median time from starting Chinese herbs to the occurrence of liver injury (LI) was 30 days (15-75 days), and 511 cases (85.9%) were classified as hepatocellular injury. Chinese herbs inducing HILI were mainly used for skin disease (102 cases, 17.1%), osteoarticular disease (57 cases, 9.6%), and gastrointestinal disease (49 cases, 8.2%), covering 207 kinds of Chinese patent medicines. Polygonum multiflorum, Psoralea corylifolia, and Corydalis ambigua were often seen in Chinese prescriptions. In RUCAM scoring, 451 HILI patients (accounting for 74.1%) were very possibly associated with Chinese herbs. Liver failure occurred in 47 HILI patients (accounting for 7.9%), cirrhosis in 45 patients (accounting for 7.6%), chronic HILI in 80 patients (accounting for 13.4%), 27 (4.5%) died, and only 2 (0.3%) underwent liver transplantation.</p><p><b>CONCLUSIONS</b>Chinese herbs could cause LI or even death. Attention should be paid to herbal hepatotoxicity and improving monitoring system of HILI.</p>

Effects of lamivudine on growth of intestinal characteristic bacteria by microcalorimetry in vitro / 药学学报

The study is aimed to investigate the effect of lamivudine on growth and metabolism of three intestinal characteristic bacteria (namely, Bifidobacterium adolescentis, Escherichia coli and Shigella dysenteriae). The growth condition of the three bacteria was quantitatively evaluated by microcalorimetry with four characteristic parameters of the thermal power-time curves, including the growth rate constant (k), thermal power (p), time to peak (t) and calorific value (Q). The results showed that the IC50 value of lamivudine on B. adolescentis was 200 microg x mL(-1), and the IC50 values of lamivudine on S. dysenteriae and E. coli were higher than 3 000 microg x mL(-1) and 6 000 microg x mL(1), respectively. Therefore, lamivudine made different inhibitory effects on the three bacteria, in which the B. adolescentis was most susceptible to lamivudine. This work showed that taking lamivudine chronically is likely to affect the balance of good flora in the intestinal tract, and might increase endotoxin release, leading to inflammation and disease progression in hepatopathy.

Microcalorimetric investigation on the interaction of six alkaloids from rhizoma coptidis / 药学学报

How to identify active constituents of traditional Chinese medicines (TCMs) and study their interactions are key problems in the development of TCMs. The inhibitory effect of six alkaloids from Rhizoma Coptidis (RC) on Shigella dysenteriae (S. dysenteria) growth had been investigated by microcalorimetry in this study. Main active constituents of RC were confirmed by comparing their contributions to the bacteriostatic effect, and the interactions among active constituents were further researched. According to the result, in 0.8 mg-mL-1 extract of RC, the contributions of six active alkaloids including berberine, coptisine, epiberberine, palmatine and the combination of jatrorrhizine and columbamine were 52.83%, 36.31%, 2.49%, 4.27% and 3.21%, respectively. Therefore, berberine and coptisine were the main active constituents of RC that inhibited the growth of S. dysenteria. The study of interactions among the six alkaloids indicated that, 1 there were some contstituents antagonizing the inhibitory effect of RC, 2 there was a synergy effect between berberine and coptisine, 3 there were additive effects between other four alkaloids and the main active constituents. These results may provide some useful references for the establishment of the quality standard for RC and the development of multi-component TCMs.

Relationship between colorectal adenocarcinoma with invasive micropapillary carcinoma component and lymph node metastasis / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between colorectal adenocarcinoma with invasive micropapillary carcinoma (IMPC) component, lymphovascular invasion, and lymph node metastasis.</p><p><b>METHODS</b>One hundred and thirty one cases of colorectal adenocarcinoma with invasive micropapillary carcinoma component were evaluated by H&E and immunohistochemical staining. The main pathological features, percentage of IMPC component, lymphovascular invasion, and lymph node metastasis were assessed and compared to 296 cases of conventional colorectal adenocarcinoma.</p><p><b>RESULTS</b>The maximum diameter of the tumors of the IMPC group was significantly lower than the conventional group. The degree of differentiation, the lymph node metastatic rate, the average number of metastatic lymph nodes, the number of cases with lymphovascular tumor emboli were significantly higher in the IMPC group (P = 0.000). The rate of distant metastasis at operation was higher in the IMPC group (14.5%) compared to the conventional group (10.8%) even though statistical significance was not achieved (P = 0.278) . In IMPC group, as the IMPC component increased, the rate of lymph node metastasis also showed an increasing trend. The rate of lymph node metastasis were 53.0% (157/296) , 67.7% (42/62) and 85.5% (59/69) " respectively" for conventional adenocarcinoma, adenocarcinoma with ≤ 10% IMPC component and adenocarcinoma with > 10% IMPC component; the difference was statistically significant (P = 0.000).</p><p><b>CONCLUSIONS</b>Compared to conventional colorectal adenocarcinomas, the colorectal carcinomas with IMPC component show a significantly higher rate of lymphovascular invasion, lymph node metastasis and distant metastasis. The percentage of IMPC component in colorectal adenocarcinoma is significantly correlated to the rate of lymph node metastasis. Therefore, presence of IMPC component and degree of tumor differentiation are predicting factors of lymph node metastasis.</p>

Inhibition effects of all trans-retinoic acid on the growth and angiogenesis of esophageal squamous cell carcinoma in nude mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The potential application of retinoic acid receptor activators, such as all trans-retinoic acid (ATRA), for treating various cancers have been studied both pre-clinically and clinically. Whether ATRA has an anticancer effect on human esophageal squamous cancer cell (ESCC) is still unknown. We have explored the anticancer effect of ATRA in ESCC, and in this study, the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor (VEGF) signal transduction pathway in transplantable tumor growth of the human ESCC cell line, EC9706, in nude mice.</p><p><b>METHODS</b>The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice. Reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues.</p><p><b>RESULTS</b>Compared to the control group, the tumor inhibition rates in the low dose ATRA, high dose ATRA, and 5-FU groups were 83.21%, 88.32%, 91.02%, respectively. The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group (P < 0.05). The study also revealed that ATRA specifically down-regulated VEGF and the component of the VEGF signal transduction pathway of CD31, CD34, and CD105 (component of the TGF-β receptor) in ESCC xenograft tissues (P < 0.05).</p><p><b>CONCLUSIONS</b>ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice. These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction, which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells.</p>

Correlation of TOP2A gene expression and survival of breast cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to assess the TOP2A RNA expression and the relationship of TOP2A protein expression with metastasis-free interval in breast cancer patients.</p><p><b>METHODS</b>TOP2A expression was analyzed prior to surgery in 86 patients. The level of TOP2A gene amplification was analyzed by fluorescence in situ hybridization (FISH), its RNA expression level with RT-PCR, and their correlation with TOP2A protein expression was assessed by immunohistochemistry (IHC). The correlation between RNA expression level and metastasis-free interval in breast cancer patients was also analyzed.</p><p><b>RESULTS</b>Aberrations (amplification or deletion) of TOP2A copy number was observed in 25.6% (22/86) of the cases. TOP2A protein expression was detected in 66.3% (57/86) of the samples. There was a significant correlation between the TOP2A RNA expression and protein expression (P < 0.001). TOP2A gene expression was significantly associated with the metastasis-free interval in the breast cancer patients (P = 0.001). There was no significant correlation between TOP2A gene amplification and TOP2A protein expression (P = 0.211).</p><p><b>CONCLUSIONS</b>TOP2A RNA level is an objective and reliable prognostic indicator in breast cancer.</p>

Expression of IGF-1R in esophageal squamous cell carcinoma and the effect of its silencing by siRNA on the proliferation of esophageal cancer EC9706 cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the correlation of IGF-1R expression with clinical features of esophageal squamous cell carcinoma (ESCC) and to investigate the effect of silencing IGF-1R by siRNA on the proliferation of esophageal cancer cell line EC9706 cells.</p><p><b>METHODS</b>Immunohistochemistry was used to detect the expresion of IGF-1R in 80 specimens of ESCC and 18 specimens of normal esophageal mucosa. IGF-1R siRNA was transfected into esophageal squamous cell carcinoma EC9706 cells, and the effect of RNAi was assessed by Western blot. The proliferation of EC9706 cells was determined by drawing growth curve, MTT assay and plate colony-forming assay.</p><p><b>RESULTS</b>The total and strong positive rates of IGF-1R expression were 86.3% and 51.3% in ESCC, and 61.1% and 11.1% in normal esophageal epithelium, respectively. The total and strong positive rates of IGF-1R expression in patients with lymph node metastasis were 94.4% and 74.1%, significantly higher than 69.2% and 3.9%, respectively, in those without lymph node metastasis (P<0.01). A significantly higher IGF-1R expression was associated with lower histological grade (P<0.05). The total and strong rates of IGF-1R expression in 39 patients of stages III and IV were 97.4% and 71.8% , significantly higher than the 75.6% and 31.7%, respectively, in 41 cases of stages I and II (P<0.01). IGF-1R RNAi significantly inhibited IGF-1R expression and the growth of EC9706 cells. The clone formation rate of RNAi-IGF-1R transfected cells was 19.1%, significantly lower than that of 52.3% in non-transfected cells and 49.0% in empty vector-transfected EC9706 cells (P<0.05).</p><p><b>CONCLUSIONS</b>The overexpression of IGF-1R is colerated with lymph node metastasis, differentiation and clinical stage. Down-regulation of IGF-1R can inhibit the proliferation of esophageal cancer EC9706 cells in vitro.</p>

Promoting effect of all-trans retinoic acid on the chemosensitivity of esophageal cancer EC9706 cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the impact of all-trans retinoic acid (ATRA) on chemosensitivity to esophageal squamous cell carcinoma EC9706 cells in vitro and its mechanism.</p><p><b>METHODS</b>EC9706 cells were routinely cultured as the control group. The experimental group was divided into three groups. The ATRA group with ATRA in final concentration of 1 µmol/L; the 5-Fu group with 5-Fu in final concentration of 50 mg/L; the combined treatment group with ATRA in final concentration of 1 µmol/L and 5-Fu 50 mg/L. The cell apoptosis was detected by terminal deoxynucleotidy transferase mediated dUTP nick end labelling (TUNEL). The cell cycle and apoptosis were detected by flow cytometry.</p><p><b>RESULTS</b>The results of TUNEL showed that in the combined treatment group appeared a large number of apoptotic cells, and their nuclei were stained brown, with a positive rate of 89.7%. There was a significant difference in the comparison with the ATRA group (38.3%) and 5-Fu group (40.3%) (P < 0.05). The flow cytometry showed that the ATRA + 5-Fu group had a significantly higher apoptosis rate (76.9% ± 2.7%) than that in the ATRA group (38.2% ± 2.6%) and 5-Fu group (45.2% ± 2.3%) (P < 0.05). The ratio of cells in G(1) phase increased in the ATRA + 5-Fu group (83.4% ± 3.0%), significantly higher than (48.2% ± 2.5%) in the ATRA group and (53.2% ± 2.6%) in the 5-Fu group (P < 0.05). The ratio of cells in S + G(2)/M phase was decreased in the ATRA + 5-Fu group, with a significant difference (P < 0.05) when compared with other groups. There was no significant difference between the ATRA group and 5-Fu group (P > 0.05) in the apoptosis rate and the proportion of cells at different phases.</p><p><b>CONCLUSION</b>ATRA can induce apoptosis of esophageal carcinoma EC9706 cells in vitro. The combination of ATRA and 5-Fu may enhance the chemotherapeutic efficacy.</p>

Mechanism of apoptosis of esophageal cancer EC9706 in nude mice induced by all-trans retinoic acid / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of apoptosis of EC9706 tumor-bearing nude mice induced by all-trans retinoic acid (ATRA).</p><p><b>METHODS</b>Human esophageal carcinoma cell line EC9706 cells were inoculated into nude mice to establish the solid tumor model. The tumor models were divided into the following groups: ATRA group, fluorouracil group, the two-drugs combination group, and with an equal volume fraction of solvent as the control group. The nude mice were sacrificed after 10 days of medication. TUNEL staining was used to detect cell apoptosis. RT-PCR was used to detect the expression level of mRNA and immunohistochemistry was used to detect the expression level of protein of caspase-3 and survivin, the apoptosis-related genes in the tumor tissue.</p><p><b>RESULTS</b>The apoptosis rates of the ATRA group, 5-Fu group and ATRA + 5-Fu group were 44.3%, 39.7% and 91.0%, respectively. There was a significant difference in comparison with the control group (0.7%), and the ATRA group had no significant difference compared with that of the fluorouracil group (P > 0.05), but the apoptosis rate of the two-drugs combination group was significantly higher than that in the two single-drug groups (P < 0.05). The average gray value of caspase-3 protein expressed in the control group was 46.12 ± 0.33 and the relative expression of caspase-3 mRNA was 0.14 ± 0.03, both were significantly lower than that in the ATRA group, 5-Fu group and the two-drugs combination group (P < 0.05). The average gray value of survivin protein expressed in the control group was 96.07 ± 0.13 and the relative expression of survivin mRNA was 0.84 ± 0.04, both were significantly higher than those of other groups (P < 0.05). The ATRA group had no significant difference compared with the fluorouracil group (P > 0.05), but the two-drugs combination group was significantly different compared with the single-drug groups (P < 0.05).</p><p><b>CONCLUSION</b>Apoptosis in the EC9706 tumor cells in nude mice can be induced by ATRA. The mechanism may be related with down-regulation of the level of survivin gene expression and up-regulation of the level of caspase-3 gene expression.</p>

Effects of endothelin-1 on the cytoskeleton protein F-actin of human trabecular meshwork cells in vitro / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the effect of endothelin-1(ET-1) on the cytoskeleton protein F-actin of cultured human trabecular meshwork (HTM) cells. METHODS: Cultured HTM cells were randomly divided into four groups: control group(0mol/L), low-dose ET-1(10-9mol/L) treatment group, middle-dose ET-1(10-8 mol/L) treatment group, and high-dose ET-1(10-7 mol/L) treatment group. After treated with ET-1, the expression of cytoskeleton protein F-actin in trabecular meshwork was analyzed with Western-blot and the distribution of F-actin was detected with FITC-Phalloidin probe. RESULTS: ET-1 dose-dependently and significantly increased F-actin in trabecular meshwork cells. The F-actin stress fiber and periphery actin fiber highly increased and manifested mild reorganization after treated with ET-1; and there were much more cell-to-cell and cell-to-extracellular matrix attachments formation in ET-1 treated HTM cells than that in the untreated HTM cells. CONCLUSION: ET-1 promoted the expression of cytoskeleton protein F-actin and induced the trabecular meshwork actin cytoskeleton reorganization.

Influence and mechanism of He-Ne laser on scar formation of filtration canal after trabeculectomy in rabbit / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the influence of He-Ne laser on connective tissue growth factor (CTGF) expression and collagen formation of fibroblast in filtration site after trabeculectomy in rabbit, and to discuss the mechanism for preventing scar formation with He-Ne laserin vivo.METHODS: The upper nasal limbus area next to the upper rectus muscle in right eyes Received 10 minutes He-Ne laser irradiation (200mW/cm2) every day for three days, the left eyes served as control. Twenty-four hours after the last irradiation, both eyes of the rabbits were took trabeculectomy surgery. The expressions of CTGF in the filtration area were tested on the 7th, 14th and 28th day after surgery and collagen density was tested on the 14th and 28th day after surgery. Each of the time point had 7 rabbits. RESULTS: The expression of CTGF was lower than that of the control group's on the 7th and 14th day after trabeculectomy surgery (P=0.01, P=0.005). When examined on the 14th and 28th day, the collagen density of irradiation group were significantly lower than that of the control group's (P=0.013, P=0.01).CONCLUSION: Pretreating the filtration area with 200mW/cm2 He-Ne laser may be helpful in preventing scar formation after trabeculectomy in rabbit, possibly due to downregulation of the expression of CTGF and collagen synthesis in fibroblasts. He-Ne laser may be developed into a new scar preventing method in filtration surgery.

Insulin induces anticancer cytotoxicity of 5-Fu to two human colon cancer cell lines / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the possibility of use of insulin as a potentiator of 5-Fu to human colon cancer cell lines HCT-8 and HT-29 and study its mechanism.</p><p><b>METHODS</b>MTT assay was used to examine the inhibition rate of cell growth after treatment with 5-Fu and insulin. Cell cycle was determined by flow cytometry.</p><p><b>RESULTS</b>Insulin showed an enhancing effect on the chemotherapeutic response of 5-Fu when insulin was applied at a dose of exceeding 0.8 mU/ml 0 approximately 8 h before 5-Fu. Within the range of from 0.8 mU/ml to 8 mU/ml, a higher concentration of insulin gave a higher proportion of inhibited cells. But when the insulin concentration exceeds 8 mU/ml, the proportion became stable as that of 8 mU/ml. Insulin increased the percentage of S phase cells and decreased the percentage of G(1) phase cells (P < 0.01). The percentage of S phase cells reached a peak when the cells were treated with insulin for 6 hours.</p><p><b>CONCLUSION</b>Insulin can enhance the anticancer toxicity of 5-Fu to human colon cancer cell lines HCT-8 and HT-29 cells. Insulin increases the percentage of S phase cells, which may be one of the main mechanisms of insulin-induced enhancement of anticancer response of cancer cells to 5-Fu chemotherapy.</p>

Isolation and identification of swine NDV JL01 strain and phylogenetic analysis of F gene / 病毒学报

An outbreak of fever and dyspnea with high incidence rate and case fatality rate occurred among pigs in a pigfarm in Jilin province, China, in 2000. The paramyxovirus-like particles could be observed in lungs, spleens and kidneys of the dead pigs under the transmission electron microscope. A Newcastle disease virus (NDV) isolate designated as JL01 was determined as the causal agent for the disease outbreak. The purified virus was reinoculated into pigs, and then the pigs infected with the virus showed similar symptoms, and the HI antibody of NDV could be detected from the reinoculated pigs. The MDT, ICPI and EID50 of the JL01 isolate was 55.2h, 1.60 and 10(-7.5)/0.1 mL respectively. The F gene of JL01 was cloned and sequenced, and the results showed that the identities of F gene shared by JL01 and avirulent NDV reference strains were from 91.5% to 98.5%, and could be ascribed to NDV genotype I. Thus, the swine NDV JL01 strain should be an avirulent strain with gene variation, but the virulence of JL01 was just the same as velogenic strains.