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Objective: T lymphocyte exhaustion is an important component of immune dysfunction. Therefore, exploring peripheral blood-exhausted T lymphocyte features in patients with hepatitis B virus-related acute-on-chronic liver failure may provide potential therapeutic target molecules for ACLF immune dysfunction. Methods: Six cases with HBV-ACLF and three healthy controls were selected for T-cell heterogeneity detection using the single-cell RNA sequencing method. In addition, exhausted T lymphocyte subpopulations were screened to analyze their gene expression features, and their developmental trajectories quasi-timing. An independent sample t-test was used to compare the samples between the two groups. Results: Peripheral blood T lymphocytes in HBV-ACLF patients had different differentiation trajectories with different features distinct into eight subpopulations. Among them, the CD4(+)TIGIT(+) subsets (P = 0.007) and CD8(+)LAG3(+) (P = 0.010) subsets with highly exhausted genes were significantly higher than those in healthy controls. Quasi-time analysis showed that CD4(+)TIGIT(+) and CD8(+)LAG3(+) subsets appeared in the late stage of T lymphocyte differentiation, suggesting the transition of T lymphocyte from naïve-effector-exhausted during ACLF pathogenesis. Conclusion: There is heterogeneity in peripheral blood T lymphocyte differentiation in patients with HBV-ACLF, and the number of exhausted T cells featured by CD4(+)TIGIT(+)T cell and CD8(+)LAG3(+) T cell subsets increases significantly, suggesting that T lymphocyte immune exhaustion is involved in the immune dysfunction of HBV-ACLF, thereby identifying potential effective target molecules for improving ACLF patients' immune function.
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Humans , Hepatitis B virus , Acute-On-Chronic Liver Failure/pathology , Hepatitis B, Chronic , T-Lymphocyte Subsets/pathology , Receptors, ImmunologicABSTRACT
Polygoni Mulitiflori Radix, or dried root tuber of Polygonum multiflorum(PM), is a traditional Chinese tonic medicine, with the effect in nourishing liver and kidney, and benefiting blood essence and hair. It is widely used in clinical and healthcare products. In recent years, more and more reports about adverse reactions of root tuber of P.multiflorum and its preparations have been reported. Fortunately, there is also substantial progress in the experimental study on liver injury induced by PM. According to the literature review, the possible causes of liver injury were found to be the mixture of raw and processed PM and long-term high-dose administration. In addition, the liver injury induced by PM is idiosyncratic liver injury, and individual factors are also the important cause. At the same time, according to the literature reports, the effects of chemical components in different pathological animal models were summarized, finding that 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside was the main component for liver injury; based on the clinical manifestations of liver injury induced by PM, the effects of some chemical components on bilirubin and bile acid metabolism were analyzed. This paper reviews the study progress of liver injury induced by PM.
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Animals , Chemical and Drug Induced Liver Injury , Drugs, Chinese Herbal , Plant Roots , PolygonumABSTRACT
Aspergillus flavus is a pathogenic fungus, which can easily contaminate Chinese herbal medicines, food, and agricultural commodities. Aflatoxin (AFT) produced by the secondary metabolism of A. flavus caused serious threats to the health of people and animals due to its carcinogenic and highly toxic characteristics. Therefore, the search for inhibitors to A. flavus and its toxins has been widely concerned in the world. Essential oil is a natural antifungal agent extracted and highly concentrated from higher plants. It has the advantages of good antifungal effect, low pollution, and relatively safe to human body. Some kinds of them, including Thymus vulgaris, Origanum virens, Perilla frutescens, Foeniculum vulgare, and so on, displayed their antifungal activities. Specifically, active ingredients such as alcohols, aldehydes, and phenols have relatively good antifungal effects. The research progress on pathogenicity of A. flavus and AFT and the prevention and control by essential oils are reviewed in this article, which provided a reference for further exploring the antifungal mechanism of essential oils and developing natural and green antifungal products.
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Ischemia-reperfusion (IR) is one of the significant medical problems in China. Triphenyltetrazolium chloride (TTC) stainingis used to detect the status of the infarct size, and real-time PCR and western blotting are used to detect expressions ofgenes. TUNEL assay has been used to detect apoptosis. Using a tree shrew myocardial IR model, we found that in thereperfusion period, resina draconis (RD) treatment reduced the infarct size by TTC staining, and significantly enhanced thesuperoxide dismutase expression and down-regulated the malondialdehyde concentration in a dose-dependent manner. Inhearts showing IR, Bax was increased and Bcl-2 was reduced, and RD treatment inhibited the IR-induced Bax expressionand up-regulated the IR suppressed level of Bcl-2. TUNEL assay showed that IR induced the apoptosis of myocardial cells,and RD treatment suppressed the IR-induced apoptosis. CHOP and GRP78 were also upregulated in IR hearts, and RDtreatment could significantly attenuate the CHOP and GRP78 levels compared with IR group. We further found that IRdecreased the miR-423-3p expression and upregulated its target gene ERK both in mRNA and protein levels, and RDtreatment upregulated miR-423-3p expression and downregulated ERK expression compared with the IR group. Importantly, miR-423-3p mimics inhibited IR increased ERK, CHOP and GRP78 expressions, and enhanced IR decreased Bcl-2expression, and inhibited the IR-induced apoptosis of myocardial cells. The findings of this study suggest that RD treatmentinhibited the endoplasmic reticulum induced apoptosis of myocardial cells via regulating miR-423-3p/ERK signalingpathway in a tree shrew myocardial IR model.
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Objective To develop a method to determine the encapsulation efficiency of doxorubicin hydrochloride and timosaponin AIII co-loaded liposomes. Methods In this paper, the thin-film rehydration method was used to prepare doxorubicin hydrochloride and timosaponin AIII co-loaded liposomes. Liposomes and free drugs were separated by dialysis, gel microcolumn centrifugation, and ultra-high speed centrifugation. The content of free drugs and drugs in liposomes was determined by HPLC, and the entrapment efficiency of doxorubicin hydrochloride and timosaponin AIII co-loaded liposomes was calculated. Results The optimal formulation of doxorubicin hydrochloride and timosaponin AIII co-loaded liposomes was DPPC-DSPE-PEG2000-TAIII-DOX with a molar ratio of 5:1:1:1. The liposomes prepared using thin-film rehydration method had a well-defined spherical shape with a size of (55.4 ± 0.40) nm, a PDI of (0.20 ± 0.02), and a weakly negative zeta potential of (-17.4 ± 0.6) mV. The excipients in the liposomal formulation can be well separated from doxorubicin hydrochloride and timosaponin AIII in the selected chromatographic conditions. The calibrated linear curve of doxorubicin hydrochloride was within 24.9-498.0 μg/mL (r = 0.999 9) and that of timosaponin AIII was within 50.55-1 011.0 μg/mL (r = 0.999 6). Free doxorubicin hydrochloride and timosaponin AIII were well separated from liposome by gel microcolumn centrifugation, and the encapsulation efficiency of doxorubicin hydrochloride and timosaponin AIII was (85.12 ± 1.27)% and (76.51 ± 0.46)% respectively. Conclusion The thin-film dispersion- method can be used for the preparation of doxorubicin hydrochloride and timosaponin AIII co-loaded liposomes. The method of gel microcolumn centrifugation is accurate, reproducible, simple, and suitable for determination of the encapsulation efficiency of co-loaded liposomes.
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A method was established for the determination of chlorpyrifos metabolites employing QuEChERS method and ultra performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry (UPLC-QTRAP). The urine samples were extracted by acetonitrile and then cleaned up with PSA and GCB. The samples were separated with the gradient elution of acetonitrile-0.2% ammonia water on ZORBAX Eclipse Plus C18column. The analytes were detected by tandem mass spectrometry under negative ion mode with electrospray ionization (ESI) source and MRM-IDA-EPI mode. Under the optimized conditions, the calibration curve was linear in range of 1.0-100.0 μg/L,and the limits of detection were 0.10-0.73 μg/L. The average recoveries were 80.3%-90.1%, and RSDs were all within 10%. The developed method was simple,sensitive,accurate,and repeatable,and could avoid false positive result of samples effectively. The established method was successfully applied to determine the exposure level of chlorpyrifos metabolites in real samples of human health risk analysis. The results showed that the maximum concentration of chlorpyrifos metabolites was 54.6 μg/L. This method provided technic support for simultaneous identification and quantification of chemicals in complex matrix.
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Objective:To evaluate the predictive value of pretreatment platelet-to-lymphocyte ratios (PLRs) in response to neoad-juvant chemotherapy and prognostic outcome in patients with International Federation of Gynecologists and Obstetricians (FIGO) Stag-es IB2-IIB cervical cancer. Methods:An investigation was conducted from January 2010 to December 2012 on 75 patients with FIGO Stages IB2-IIB cervical cancer, who underwent neoadjuvant chemotherapy and radical surgery in Changhai Hospital, Shanghai. A re-ceiver operating characteristic (ROC) curve was used to determine the best PLR cut-off value in predicting the response to neoadjuvant chemotherapy. The relationships between the pretreatment variables and the response to neoadjuvant chemotherapy were assessed in univariate and multivariate settings. The overall three-year survival rates were analyzed using the log-rank test and Cox regression mod-el. Results:The response to neoadjuvant chemotherapy was associated with PLR. At the threshold of 123.0, the PLR was 88.5%sensi-tive and 52.2%specific. Multivariate analysis showed that the low independent PLR predicted the response to neoadjuvant chemothera-py well. Based on the log-rank test, the three-year survival rate was lower in patients with PLR >123.0 than those with PLR 4 cm in diameter) and lymph node metastasis influenced the three-year survival rate. In the Cox regression model, only the lymph node metastasis was identified as an independent risk factor for poor prognosis (RR:5.375;95%CI:1.351-21.379; P=0.017). Conclusion: Pretreatment PLR is an easily measured, reproducible, and inexpensive marker of systemic in-flammation and thus shows a prognostic and independent predictive value for the response to neoadjuvant chemotherapy in cervical can-cer. However, pretreatment PLR is not a clinically significant factor for the assessment of cervical cancer prognosis.
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<p><b>OBJECTIVE</b>To evaluate the inhibitory effect of Nandeshi, an acrosin inhibitor, on human acrosin activity.</p><p><b>METHODS</b>We collected sperm samples from 10 healthy fertile men and cultured them with Nandeshi at 30 degrees C for 5 minutes at the concentrations of 0. 100, 0.120, 0.144, 0.173, 0.207, 0.249, 0.299, 0.358 and 0.430 mmol/L, with the controls treated with a well-known acrosin inhibitor N-alpha-p-tosyl-L-lysine chloromethylketone (TLCK) at 150.0, 189.8, 213.6, 240.3, 270.3, 304.1 and 342.1 mmol/L. Then we determined the residual activity of human acrosin by improved Kennedy assay.</p><p><b>RESULTS</b>The residual activity of acrosin was negatively correlated with the Nandeshi concentration, and Nandeshi exhibited an inhibition rate about 800 times that of TLCK.</p><p><b>CONCLUSION</b>Nandeshi has a powerful inhibitory effect on human acrosin, and improved Kennedy assay is a simple, practical and highly sensitive technique for the detection of human acrosin activity.</p>
Subject(s)
Humans , Male , Acrosin , Metabolism , Contraceptive Agents, Female , Pharmacology , Enzyme Inhibitors , Pharmacology , Spermatozoa , Tosyllysine Chloromethyl Ketone , PharmacologyABSTRACT
Teaching method is important to carry through the content of the course and guarantee the teaching quality.We have proceeded some reforms and research in the Obstetrics and Gynecology teaching and have obtained the good result by intergroting teaching conteut and teaching resoures,selecting high-level teaching team,case teaching,PBL teaching and multi-media teaching.
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Objective To compare effects between laparoscopy and laparotomy for the treament of ovarian endometriosis cysts and to investigate the value of laparoscopy in the treatment of ovarian endometriosis cysts. Methods We retrospectively analyzed 144 cases of ovarian endometriosis cysts,92 of which underwent laparoscopic operations(Laparoscopic Group) and 52 of which received open operations(Open Group).All the cases were followed for 4 months ~ 5 years.Results The operation time,postoperative hospital stay,and intraoperative blood loss were 69?41.8 min,3.5?1.0 d,and 55?12.0 ml in the Laparoscopic Group,respectively,and 137?54.3 min,8.7?3.5 d,and 178?105.9 ml in the Open Group,respectively,with significant differences between the two groups(t=-8.402,-11.048,and-13.350;P=0.000).There was no significant difference in the rate of abdominal pain relief between the Laparoscopic Group(66.0%,35/53) and the Open Group(52.8%,19/36)(?~2=1.580,(P=0.209)).The recurrent rate was 19.6%(18/92) in the Laparoscopic Group and 19.2%(10/52) in the Open Group,without significant difference between the two groups(?~2=0.002,P=0.961). Conclusions Laparoscopic surgery gives similar efficacy to open surgery in the treatment of ovarian endometriosis cysts.Laparoscopic surgery can be used as the first choice in treating ovarian endometriosis cysts because of its minimally invasive characteristics.
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Objective To evaluate the value of combined use of laparoscopy and hysteroscopy in the diagnosis of infertility. Methods Clinical data of 168 cases of infertility receiving examinations with laparoscopy and hysteroscopy from June 1999 to October 2003 were retrospectively reviewed.Results Hysteroscopic examinations found intrauterine diseases in 79 cases(79/168,47.0%),including 46 cases of endometrial hyperplasia or polyps(46/79,58.2%).Laparoscopic examinations showed organic pelvic diseases in 99 cases,including 85 cases of chronic pelvic inflammation,endometriosis or polycystic ovarian syndrome(85/99,85.9%).Both laparoscopy and hysteroscopy gave normal findings in 15 cases and abnormal findings in 39 cases.Unilateral or bilateral tubal obstruction was found in 90 cases by tubal patency tests under hysteroscope(90/168,53.6%) and in 78 cases by laparoscopy(78/168,46.4%). Conclusions Combined use of laparoscopy and hysteroscopy offers accurate diagnostic evidences in examinations of infertility.
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<p><b>OBJECTIVE</b>To observe the effects of retinoic acid (RA) on the proliferation and differentiation of a human ovarian carcinoma cell line: 3AO cells.</p><p><b>METHODS</b>3AO cell proliferation was evaluated by viable cell count, percentage of cells in each cycle phase were analyzed by flow cytometric analysis, alkaline phosphatase (AKP) activity was determined as described, and CA125 expression was measured by ELISA.</p><p><b>RESULTS</b>RA could inhibit the proliferation of 3AO cells accompanied with morphological changes in a dose-dependent manner. Cell cycle analysis indicated that RA inhibition of 3AO cells growth occurred through induction of G1 arrest with a concomitant reduction in the proportion of cells in S phase, AKP activity increased significantly after treatment with RA (0.1 micromol/L) for 1-5 days. Dose-response studies revealed that the AKP activity increased to a different extent as a function of RA concentrations. Furthermore, RA could suppress the expression of CA125 tumor marker in 3AO cells.</p><p><b>CONCLUSION</b>RA could markedly inhibit the proliferation and induce the differentiation of 3AO cells.</p>
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Female , Humans , Alkaline Phosphatase , Metabolism , Antineoplastic Agents , Pharmacology , Biomarkers, Tumor , Cell Cycle , Cell Differentiation , Cell Line, Tumor , Cell Proliferation , Dose-Response Relationship, Drug , Ovarian Neoplasms , Metabolism , Pathology , Proteins , Metabolism , Tretinoin , PharmacologyABSTRACT
Objective To investigate the activity change pattern and corresponding significance of gly- colytic enzymes including alsolase A(ALDA)and lactate dehydrogenase M(LDH-M)regulated by hy- poxia-inducible factor 1?(HIF-1?)in spinal cord injury(SCI)of rats.Methods SD rats were ran- domly divided into control group and groups at 12 hours,1,2 and 3 days,1 and 2 weeks after compres- sive SCI,in which the activity changes of ALDA and LDH-M in the injured spinal cord were observed at different time points by means of enzyme histochemistry.Results Opitical density(A)value of AL- DA continued significant increase from two days to one week after SCI(P＜0.05)and decreased gradual- ly at 2 weeks after SCI.A value of LDH-M began significant increase at day 1 after SCI and recovered to normal level at 2 weeks after SCI(P＜0.05).Conclusion Activities of ALDA and LDH-M regulated by HIF-1?in spinal cord injury is significantly increased.
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Objective The purpose of this study was to explore the teaching method PBL in gynecology and obstetric education. Methods We took PBL in teaching Acute Gynecological Abdomen Pain in 102 students between 2008 and 2009. Results Questionnaire results and high scores in tests suggested that the students showed great subjective initiative in studies.PBL can cultivate students'self-learning capability,improve their ability of analyzing and solving prob-lems. Conclusion PBL is a better way in clinical medical education and worthwhile to be further researched and carried out.
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Objective To study the expression of GPC3 mRNA and GPC3 protein in ovarian carcinoma, and to investigate the clinical significance of their expression. Methods 35 specimens of ovarian carcinomas and 23 specimens of normal ovarian tissues were obtained from the patients undergoing operation during Jan. 2004 to Oct. 2005. The expressions of GPC3 mRNA in ovarian carcinomas and normal ovarian tissues were detected by real-time fluorescence quantitative PCR (RT-PCR). The clinical and pathological characteristics of ovarian carcinomas were analyzed. The expression of GPC3 protein was detected in 4 specimens of ovarian carcinomas and 3 specimens of normal ovarian tissues by Western bloting. Results The expression level of GPC3 mRNA in ovarian carcinomatous was down-regulated compared with that in normal ovarian tissues (P0.05). The expression of GPC3 protein was consistent with the expression of GPC3 mRNA. GPC3 protein was doubly or trebly expressed in normal ovarian tissues compared with ovarian carcinomas. Conclusion The present study suggests that GPC3 may be related to the occurrence and development of the ovarian carcinoma. The simultaneous determination of GPC3 and CA125 may increase the sensitivity of diagnosis for ovarian carcinoma.
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Ovarian cancer is sex hormone-Dependent.Gonadotropin releasing hormone (GnRH) analogues inhibit ovarian cancer not only through the hypothalamus-pituitary-gonadal axis, but also through directly inhibiting the proliferation and inducing the apoptosis via GnRH receptors on the ovarian carcinoma cells.In addition, GnRH analogues target GnRH receptors on the cancer cells and can serve as a carrier for cytotoxic agents, improving the efficiency of cytotoxic agents and lowering the side effect.In a word, treatment with GnRH analogues may be a valuable alternative for advanced and recurrent ovarian cancer.
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Retrospective study was carried out in 93 cases of endometrial carcinoma admitted to our hospital since Jan. 1985 to Dec. 1994. Thirty five cases were older than 60 years, and 24 cases were younger than 50 years. All of the cases had pathological diagnosis and were staged according to FIGO. When compared with the younger group, the rate of older patients with stage Ⅰa was higher (11.4% in younger and 45.4% in older, P
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Objective To study the expression of human giant larvae-1 (Hugl-1) in ovarian carcinoma and its clinical significance.Methods Hugl-1 mRNA expression in 31 ovarian cancer and the corresponding adjacent tissues was examined by real time fluorescence quantitative RT-PCR and in situ hybridization.Moreover,analysis was done while taking into consideration of the clinicopathologic parameters of ovarian cancer.Results The expression of Hugl-1 mRNA in ovarian cancer tissue was significantly higher than that in the corresponding adjacent tissues ([0.051 ? 0.029]vs [0.026 ? 0.043],P
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Objective:To study the effect of GnRH analog triptorelin in resensitizing cisplatin-resistant human ovarian canc- er cells and to discuss the related mechanism.Methods:Cisplatin-resistant human ovarian cancer cell line OVCAR-3/CDDP was established in vitro.MTT assay was used to assess the inhibitory effects of triptorelin,cisplatin alone or a combination of both on OVCAR-3/CDDP cells.Flow cytometry was employed to observe the expression changes in epidermal growth factor receptor (EGFR)in different groups.Results:The drug restant index of OVCAR-3/CDDP cells was 13.42.The resensitizing fold of cisplatin combined with triptorelin was 3.80.The expression of EGFR had the most prominent decrease in OVCAR-3/CDDP cells in the combination group.Conclusion:Triptorelin can partially resensitize cisplatin-resistant OVCAR-3/CDDP cells,which might be related to the down-regulation of EGFR.