Research progress on mechanism of tyrosine kinase inhibitor-induced liver injury / 中国药理学通报

Tyrosine kinase inhibitors (TKIs) are a class of molecular targeted drugs that inhibit the activation of downstream signaling pathways by inhibiting oncogene-related receptor tyrosine kinases to exert anti-cancer effects. TKIs are superior to traditional chemotherapeutics in terms of selectivity, effectiveness and safety, and are widely used in the treatment of cancer. However, TKIs-induced liver injury is one of the difficult problems in its clinical application. In this article, relevant literatures from domestic and abroad are reviewed and the research progress in the classification, clinical application of TKIs and the mechanism of TKIs-induced liver injury are summarized. This review intends to provide a reference for further elucidating the mechanism of TKIs-induced liver injury, and seeking effective prevention and treatment methods.

Multimorbidity in elderly patients with acute coronary syndrome: insights from BleeMACS registry / 中华心血管病杂志

Objective: To assess the prevalence, pattern and outcome of multimorbidity in elderly patients with acute coronary syndrome (ACS). Methods: Secondary analysis was performed based on the data from the BleeMACS registry, which was conducted between 2003 and 2014. We stratified elderly patients (≥65 years) according to their multimorbidity. Multimorbidity was defined as two or more chronic diseases in the same individual. Kaplan-Meier methods were used to estimate 1 year event rates for each endpoint, and comparisons between the study groups were performed using the log-rank test. The primary endpoint was net adverse clinical events (NACE), which is a composite of all-cause mortality, myocardial infarction, or bleeding. Results: Of 7 120 evaluable patients, 6 391 (89.8%) were with morbidity (1 594 with 1, 2 156 with 2, and 2 641 with ≥3 morbidity). Patients with morbidity were older, percent of female sex and non-ST-elevation acute coronary syndromes and implantation rate with drug-eluting stents and blood creatine level were higher compared to patients without morbidity. Compared with the patients without morbidity, the proportion of participants with oral anticoagulant increased in proportion to increased number of morbidities (5.8% vs. 6.4% with 1 morbidity, 7.3% with 2 morbidities, 9.0% with ≥3 morbidities, P trend<0.01) and the proportion of participants with clopidogrel prescription decreased in proportion to increased number of morbidity (91.9% vs. 89.7% with 1 morbidity, 87.9% with 2 morbidities, 88.6% with ≥3 morbidities, P trend = 0.01). During 1 year follow-up, compared with those with no morbidity, the hazard ratio (HR) and 95% confidence interval (CI) of risk of NACE for those with 1, 2, and ≥ 3 morbidities was 1.18 (0.86-1.64), 1.49 (1.10-2.02), and 2.74 (2.06-3.66), respectively (P < 0.01). Multimorbidity was not associated with an increased risk of bleeding of various organs (P>0.05). Conclusion: Multimorbidity is common in elderly patients with ACS. These patients might benefit from coordinated and integrated multimorbidity management by multidisciplinary teams.

Influence of continuous light and benzene exposure on erythrocyte parameters and expression of miRNA-144/451 in mice / 中国职业医学

@#Abstract: Objective To explore the effects of continuous light and benzene exposure on peripheral blood erythrocyte - Methods parameters and expression of miR 144/451 in the bone marrow of mice. This was a 2×2 factorial design. Photoperiod ， ， factor was set as normal and continuous light levels and mice were treated for 12 hours/12 hours light/dark or 24 hours light - respectively. The benzene exposure factor was set as non exposure and exposure levels. Mice were exposed to benzene by static 3 ， inhalation with a mass concentration of 0.0 and 32.5 mg/m for three hours per day five days per week for a total of four weeks. ， ， Specific pathogen free male C57BL/6 J mice were randomly divided into negative control group simple continuous light group - - ， ， simple benzene exposure group and combined exposure group with 12 mice per group. After benzene exposure peripheral ， blood was collected for the detection of erythrocyte parameters in four periods. After the mice were sacrificed the expression of - - - - miR 451a and miR 144 5p was detected by real time fluorescence quantitative polymerase chain reaction in bone marrow Results （ ）， ， tissues. The hematocrit volume HCT mean corpuscular volume mean corpuscular hemoglobin concentration （ ） - MCHC and mean corpuscular hemoglobin in peripheral blood and the relative expression of miR 451a in bone marrow tissue （ P< ） ， were statistically significant only in mice with benzene exposure all 0.05 . Among them the MCHC of benzene exposed （P< ）， （ P< ） - mice increased 0.05 but the other four indexes decreased all 0.05 compared with non benzene exposed mice. In thenegative control group the change of red blood cells count hemoglobin level and HCT in peripheral blood were rhythmical all P < ） ， （ P > ） rhythmical 0.05 . However the indexes above were out of rhythm all rhythmical 0.05 in the simple continuous light group and the - （ P > combined exposure group. The change of hemoglobin level and HCT of peripheral blood were also out of rhythm all rhythmical ） - - 0.05 in the simple benzene exposure group. The relative expression of miR 451a in bone marrow tissues of negative control （ P < ）， - group and simple continuous light group was rhythmical all rhythmical 0.05 while the relative expression of miR 451a in simple - - （ P > ）Conclusion benzene exposure group and combined exposure group was out of rhythm all rhythmical 0.05 . Benzene exposure ， induced changes in erythrocyte parameters of mice are independent effect and its mechanism may be related to the rhythmic - ， expression disorder of miR 451a in bone marrow tissues. Continuous light exposure benzene exposure and their interactions can ， interfere with the circadian rhythm of erythrocyte parameters such as red blood cell count hemoglobin and HCT to some extent.

Impact of obstructive sleep apnea on the long-term cardiovascular outcomes in patients with acute coronary syndrome / 中华心血管病杂志

Objective: To investigate the impact of obstructive sleep apnea (OSA) on long-term cardiovascular outcomes in patients with acute coronary syndrome (ACS). Methods: This is a single-center, prospective cohort study. Between June 2015 to January 2020, consecutive ACS patients hospitalized at Beijing Anzhen Hospital, Capital Medical University were enrolled. All patients underwent portable sleep breathing monitoring, and they were then divided into moderate/severe OSA group (apnea-hypopnea index (AHI)≥15 events/hour) and no/mild OSA group (AHI<15 events/hour). The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, ischemia-driven revascularization and hospital admission for unstable angina or heart failure. MACCE were compared yearly by the log-rank test. Multivariable Cox regression analyses were performed to determine the independent predictors of MACCE. Results: A total of 1 927 patients with ACS were enrolled, including 1 629 males (84.5%), aged (56.4±10.5) years. Moderate/severe OSA was present in 1 014 (52.6%) patients. Compared with no/mild OSA group, moderate/severe OSA group exhibited a higher body mass index (P<0.05). Hypertension, prior PCI were more prevalent in moderate/severe OSA group (both P<0.05). The difference of ACS category between the two groups was statistically significant (P=0.021). The rate of patients who underwent PCI and the number of stents were higher in the moderate/severe OSA group. During a 5-year follow-up (median 2.9 years (IQR 1.5-3.6 years)), the cumulative incidence of MACCE was significantly higher in the moderate/severe OSA group than in the no/mild OSA group (34.0% vs. 24.0%, HR=1.346, 95%CI 1.100-1.646, log-rank P=0.004). The cumulative incidence of MACCE remained statistically higher at 4 and 5 year in the moderate/severe OSA group as compared to the no/mild OSA group (33.3% vs. 22.9%, HR=1.397, 95%CI 1.141-1.710, log-rank P=0.001; 34.0% vs. 24.0%, HR=1.341, 95%CI 1.096-1.640, log-rank P=0.004, respectively). Multivariate analysis showed that moderate/severe OSA (HR=1.312, 95%CI 1.054-1.631, P=0.015) was an independent predictor of long-term MACCE in ACS patients. Conclusions: Moderate/severe OSA is observed in more than 52% ACS patients. Moderate/severe OSA is an independent predictor of long-term MACCE.

Study on emergency metabolic changes of Anopheles sinensis larvae following exposure to deltamethrin / 中国血吸虫病防治杂志

Objective To analyze the changes of small molecular metabolites in the larvae of a deltamethrin-sensitive strain of Anopheles sinensis following exposure to deltamethrin, so as to provide the scientific basis for investigating the metabolic pathway and screening metabolic markers of deltamethrin in An. sinensis. Methods The 50% and 75% lethal concentrations (LC50 and LC75) of deltamethrin against the larvae of a deltamethrin-sensitive strain of An. sinensis were calculated in laboratory. The type and content of An. sinensis larvae metabolites were detected using high performance liquid chromatography and mass spectrometry (LC-MS/MS) following exposure to deltamethrin at LC50 and LC75 for 30 min and 24 h, and the changes of metabolites were analyzed. Results The LC50 and LC75 values of deltamethrin were 4.36 × 10-3 µg/mL and 1.12 × 10-2 µg/mL against thelarvae of a deltamethrin-sensitive strain of An. sinensis. Following exposure of the larvae of a deltamethrin-sensitive strain of An. sinensis to deltamethrin at LC50 and LC75 for 30 min, the differential metabolites mainly included organic oxygen compounds, carboxylic acid and its derivatives, fatty acyl and pyrimidine nucleotides, with reduced glucose levels. Following exposure for 24 h, the differential metabolites mainly included organic oxygen compounds, carboxylic acid and its derivatives, aliphatic acyl and purine nucleotides, with increased glucose level detected. Conclusion Carbohydrate, carboxylic acid and its derivatives, fatty acyls, amino acids and their derivatives may play important roles in deltamethrin metabolism in the larvae of a deltamethrin-sensitive strain of An. sinensis.

Surveillance of Culex mosquitoes in Jiangsu Province from 2018 to 2019 / 中国血吸虫病防治杂志

Objective To investigate the distribution and density of Culex mosquito populations and the resistance of Culex pipiens pallens to insecticides in Jiangsu Province in 2018 and 2019. Methods During the period from June to October in 2018 and 2019, six counties (districts, cities) were sampled in southern, northern and central Jiangsu Province as surveillance sites. The density of Culex mosquitoes was measured overnight using the light trapping technique. In addition, Culex pipiens pallens mosquitoes were collected from Hai’an of Nantong City and Yandu District of Yancheng City, central Jiangsu Province, and the sensitivity of female first filial generations to dichlorodiphenyltrichloroethane (DDT), malation, proposur, beta cypermethrin and deltamethrin was tested using the standard WHO insecticide susceptibility test assay. Results A total of 104 423 Culex mosquitoes were captured in six surveillance sites of Jiangsu Province in 2018 and 2019, and Culex quinquefasciatus (49.11%), Culex pipiens pallens (28.38%), and Culex tritaeniorhynchus (21.04%) were predominant species. The density of Culex mosquitoes started to increase since early June, peaked in July and tended to be low in late October. Culex pipiens pallens mosquitoes captured from Hai’an was susceptible to malation, while those from Yandu District were moderately resistant to malation. Culex pipiens pallens mosquitoes from both Yandu and Hai’an were moderately resistant to proposur, and were resistant to DDT, beta cypermethrin and deltamethrin. Conclusions Culex quinquefasciatus, Culex pipiens pallens and Culex tritaeniorhynchus are predominant Culex species in Jiangsu Province. Culex pipiens pallens is resistant to DT, beta cypermethrin and deltamethrin in central Jiangsu Province.

Critical hubs of renal ischemia-reperfusion injury: endoplasmic reticulum-mitochondria tethering complexes / 中华医学杂志(英文版)

Mitochondrial injury and endoplasmic reticulum (ER) stress are considered to be the key mechanisms of renal ischemia-reperfusion (I/R) injury. Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER, known as mitochondrial-associated membranes. The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes, which can play an important role in mitochondrial damage, ER stress, lipid homeostasis, and cell death. Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury. A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets. In this review, we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms, such as mitophagy, mitochondrial fission, mitochondrial fusion, apoptosis and necrosis, ER stress, mitochondrial substance transport, and lipid metabolism.

Effect of BRWD3 on lymph node metastasis in breast cancer / 解放军医学杂志

Objective: To explore the effect of the bromodomain and WD repeat domain containing 3 (BRWD3) on lymph node metastasis in breast cancer and its mechanism. Methods: In vitro cell invasion experiments were used to explore the effect of BRWD3 on the invasion phenotype of breast cancer cell lines. Mouse lymph node metastasis model and lung metastasis model were used to investigate the role of BRWD3 in regulating breast cancer lymph node metastasis and lung metastasis in BALB/c nude mice. The BRWD3 co-expressed genes were searched through cBioPortal databases to analyze the biological functions and pathways of BRWD3, constructed a BRWD3 molecular regulatory network, which is examined with Western blotting analysis partly. The public breast cancer dataset and the KMPLOT analysis platform was used to analyze the expression of BRWD3 in breast cancer and the relationship between the expression of BRWD3 and breast cancer prognosis. Results: In vitro experiments showed that knockdown of BRWD3 significantly enhanced the invasion and migration of breast cancer cells (P<0.01), but did not promote their proliferation. The lymph node metastasis model demonstrated that knockdown of BRWD3 dramatically enhanced lymph node metastasis of breast cancer. Interestingly, the lung metastasis model showed that BRWD3 did not affect the mouse lung metastasis ability. Further functional clustering GO analysis of the co-expressed genes of BRWD3 suggested that they are mainly involved in gene expression regulation, DNA damage repair, chromosome organization and modification, ubiquitination, etc. Meanwhile, KEGG enrichment analysis showed that they were involved in signaling pathways such as ubiquitination, oxidative phosphorylation, MAPK, etc. Besides, via the Western blotting experiment, it was found that knockdown of BRWD3 increased the phosphorylation of ERK1/2. Moreover, BRWD3 expression in breast cancer with lymph node metastasis is significantly lower than in patients without lymph node metastasis. Further, the survival analysis in KMPLOT found that the prognosis of patients with low expression of BRWD3 was poor, which was significantly lower than that of patients with high expression of BRWD3. Conclusions: BRWD3 can regulate breast cancer invasion in vitro and lymph node metastasis in vivo. Afterward, the prognosis of patients with low expression of BRWD3 is poor. Meanwhile, ubiquination, oxidative phosphorylation, MAPK pathway, etc. were the possible regulation pathways of BRWD3, which provide a new theoretical basis for the research and application of molecular markers related to breast cancer lymph node metastasis.

Optimization of Electromagnetic Cracking Extraction Technology of Baicalin in Scutellariae Radix by Response Surface Methodology / 中国实验方剂学杂志

Objective: To optimize the extraction conditions of baicalin from Scutellariae Radix by electromagnetic pyrolysis. Method: Based on single factor experiments, taking extraction time, material size and liquid-material ratio as factors, yield of baicalin as index, extraction parameters were optimized by response surface methodology, and compared with ultrasonic method, ethanol refluxing method and decoction method. Result: The optimal extraction conditions were as follows:extraction time of 2.41 min, material size of 100 mesh, liquid-material ratio of 33 mL·g-1. Under these conditions, the yield of baicalin was 12.21%. The yields of baicalin by ethanol refluxing method, decoction method and ultrasonic method were 12.91%, 12.62% and 11.61%, respectively. The yield of baicalin by electromagnetic cracking extraction was close to several other conventional extraction methods, and the extraction time was significantly shortened. Conclusion: As a novel extraction technology of traditional Chinese medicine, electromagnetic cracking extraction has the advantages of high efficiency, energy and time saving, green environmental protection, etc. And it can provide a new method for the industrial extraction of baicalin.

The predictive value of PNI for post-operative intra-abdominal infections in gerontal liver cancer patients / 中国实用外科杂志

OBJECTIVE: To investigate the predictive significance of prognostic nutritional index(PNI)for intraabdominal infections(IAIs)in gerontal liver cancer patients who received hepatectomy.METHODS: The clinical data of270 gerontal(age≥60 y)patients with primary liver cancer(PLC)who received hepatectomy in the First Affiliated Hospital of Xi' an Jiaotong University were retrospectively analyzed.Receiver operating characteristic curve(ROC),multivariate analysis and survival curve were used to conduct the predictive significance of preoperative PNI for IAIs.RESULTS: The incidence of IAIs was 12.59%(34/270)in this cohort.The cut-off value of preoperative PNI for the prediction of postoperative IAIs was 47.58(P0.05).CONCLUSION: Preoperative PNI determination has predictive value for postoperative IAIs in gerontal liver cancer patients who received hepatectomy.

Presentation of the concept of "pan-complicated IAIs" and the discussion of the strategy of its diagnosis and treatment / 中国实用外科杂志

Intra-abdominal infections(IAIs)is common in the clinic which includes a variety of pathological conditions,ranging from uncomplicated appendicitis to fecal peritonitis.IAIs can be classified as healthcare-associated IAIs and community-acquired IAIs according to the circumstance of origin.IAIs can be also classified as uncomplicated IAIs and complicated IAIs according to the extent of infection.However,the circumstance of origin and extent of infection can't predict the therapy difficulty and clinical outcome.So,the authors first propose the new concept of "pan-complicated IAIs" and elaborate its clinical significance which may evoke the interest of clinicians to pay close attention to the diagnosis and treatment of IAIs.

New concept of diagnosis and treatment of intra-abdominal infections:consensus and controversies / 中国实用外科杂志

The incidence of intra-abdominal infections(IAIs)is increasing theses years which receives more and more attention in the clinic.Especially the complicated IAIs,post-operative IAIs,intra-abdominal candidiasis and abdominal sepsis get an unacceptably high mortality,which is the most difficult and dispirited for the clinicians.How to recognize these IAIs and implement adequate treatment in the early time are the keys to improve the prognosis.Early diagnosis and accurate classification are the keys to assess the severity.Effectiveinfection source control is the core of treatment.For the IAIs accompany with organ dysfunction,surgeon-predominant IAIs multiple disciplinary team(MDT)should be establish to improve the diagnosis and treatment of IAIs.

Effects of mesenteric lymph duct ligation on sepsis-induced lung and intestinal injuries in rats / 西安交通大学学报(医学版)

Objective To study the effect of mesenteric lymph duct ligation(MLDL)on sepsis-induced lung and intestinal injuries in rats.Methods Sepsis was induced by cecal ligation and puncture(CLP)in male rats.The rats were randomly divided into sham control group in which rats received sham operation,sepsis group(CLP group)in which rats received saline after CLP operation,and CLP+MLDL group in which rats received mesenteric lymph duct ligation(MLDL)after CLP operation.The rats were sacrificed at 24 h after CLP modeling. Bronchoalveolar lavage fluid,arterial blood,and intestine and lung tissues were collected to determine organ injuries.Results The lung tissue histopathology and blood gas analysis revealed that MLDL markedly alleviated the lung injury(ALI score:6.14 ± 0.51 vs.8.12 ± 0.63,P=0.029 9),improved oxygen partial pressure[(78.67 ± 4.51)mmHg vs.(64.83 ± 2.90)mmHg,P=0.0273],decreased lung W/D ratio(6.12 ± 0.25 vs.7.63 ± 0.49,P=0.021 2),decreased BALF cytokines levels[TNF-α:(828.17 ± 81.89)pg/mL vs.(1 118.17 ± 79.22)pg/mL,P=0.029 1;IL-6:(39.33 ± 5.50)ng/mL vs.(68.67 ± 5.24)ng/mL,P=0.003 4],alveolar permeability[protein levels:2.117 ± 0.289 2 vs.3.033 ± 0.164 7,P=0.020 3,and cell levels:(30.00 ± 3.587)×106/L vs.(43.83 ± 2.358)×106/L,P=0.009 1].However,according to the results of HE and biochemical detection,MLDL had no protective effect on sepsis-induced intestinal injury.Moreover,MLDL could significantly reduce the bacterial loads of the blood and lung,but do not change the bacterial level in the intestines.Conclusion MLDL has a significant protective effect on sepsis-induced lung injury mainly by decreasing bacterial translocation,but had no effect on intestinal injury.This difference may be related to that MLDL inhibits the bacteria spreading from abdominal cavity to other organs in sepsis but it causes their accumulation in the intestines.

Analysis and validation of PI3K/AKT signaling pathway associated with overall survival time of patients with HER2-positive breast cancer / 解放军医学杂志

Objective To analyze and validate the key molecular targets correlated with the overall survival of patients with HER2-positive breast cancer.Methods First,the survival time and transcriptome data of patients with HER2-positive breast cancer in stage Ⅰ / Ⅱ and Ⅲ/Ⅳ were downloaded from the TCGA database.The significantly differential genes between overall survival ＜2 years and ＞8.5 years in stage Ⅰ / Ⅱ were picked out by edgeR package,and the pathways were enriched by KEGG.Similarly,the differential genes between overall survival ＜2 years and ＞7 years in stage Ⅲ/Ⅳ were analyzed.Furthermore,KEGG pathway analysis was performed using the differential genes overlapped by stage Ⅰ /Ⅱ and Ⅲ/Ⅳ.Second,the relationships between the expression levels of key node genes and other genes in enriched pathway and the overall survival of patients with HER2-positive breast cancer were validated by KMplot database.Last,the correlation between the activity of pathway enriched in KEGG and the resistance to anti-HER2 treatment was validated in HER2-positive breast cancer cell line BT474.Results In patients with stage Ⅰ / Ⅱ HER2-positive breast cancer whose overall survival was ＜2 years,PI3K/AKT was the 9th signaling pathway enriched by up-regulated differential genes.In patients with stage Ⅲ/Ⅳ whose overall survival was ＜2 years,PI3K/AKT was the 2nd signaling pathway enriched by up-regulated differential genes.Furthermore,PI3K/AKT was the first signal pathway enriched by the overlapping upregulated genes of patients in stage Ⅰ / Ⅱ and Ⅲ / Ⅳ whose overall survival was ＜2 years.Patients with high expression of PI3K and AKT (key node genes) or CFAP221 and COL4A6 (other genes) of PI3K/AKT pathway had shorter overall survival than those with low expression.PI3K inhibitors could enhance the growth inhibitory effect of HER2 small molecule inhibitor on HER2-positive breast cancer cell line BT474.Conclusions The overexpression of PI3K/AKT pathway is associated with the shorter overall survival in HER2-positive breast cancer patients,and associated with anti-HER2 resistance in HER2-positive breast cancer cell line.

Research Progress of Desialylation in Immune Thrombocytopenia -Review / 中国实验血液学杂志

Some patients diagnosed as immune thrombocytopenia(ITP) have poor response to common first-line therapy such as corticosteroid and immunoglobulin. Studies in recent years have found a FC-independent platelet clearance pathway exists, which is characterized by desialylation of platelet surface glycoprotein(GP), recognition and phagocytosis by Ashwell-Morell receptor(AMR) on hepatocytes, independent on Fc receptors of the reticuloendothelial system. The up-regulation of neuraminidase-1(Neu1) expression on platelet caused by various factors, such as cold storage of platelet, septicemia and ITP could desialylate GPs. It has been found that ITP with positive anti-GPIbα antibody mostly has a poor response to first-line therapy and indicated that such antibody may lead to FC-independent platelet clearance. It also has been proved that anti-GPIbα antibody could desialylate GPs on platelet in animal experiments. Researchers have tris to use sialidase inhibitor agent to treat ITP and got a persistent response of platelet. Here, the desialylation of platelet and its role in ITP pathogensis and therapy are reviewed.

Case report of one child with idiopathic hypereosinophilic syndrome and literature review / 天津医药

@#Idiopathic hypereosinophilic syndrome (IHES) is a very rare disorder in children, characterized by increased eosinophils in bone marrow, peripheral blood and tissue, resulting in multiple organ damage. We report a case of an 8-yearold girl with IHES, whose initial complaints were diarrhea and abdominal distension. Image examinations indicated that the digestive tract, lung and urinary bladder were all affected. Routine blood test showed that the eosinophilia was 20.64×109/L. Bone marrow smear showed that the mature eosinophilic granulocytes increased to 32%. The FIL1P1/PDGFRA, FGFR1 and IGH gene detection, parasites and antibody tests were all negative. The diagnosis of IHES was considered. The eosinophil decreased significantly and symptoms relieved after steroid treatment, though with recurrences, steroids were still sensitive. Then we reviewed the relevant literature and cases of children with IHES in China.

Influence of drug metabolizing enzyme inhibitors on liver injury susceptibility to trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside / 药学学报

By using the drug metabolizing enzyme inhibitors, the effects of metabolic factors on potential liver injury induced by the main component, trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside(trans-SG), in Polygonum multiflorum was investigated. The main metabolic enzyme isoforms involved in trans-SG metabolism were also screened. The results showed that trans-SG at the dosage 31 mg·kg-1 did not cause liver injury; and the combination of trans-SG with the phase I metabolic enzyme inhibitor, 1-benzylimidazole (10 mg·kg-1), did not change the degree of liver injury(compared with LPS + trans-SG group, P > 0.05). However, the combination of trans-SG with phase II metabolic enzyme inhibitor, ketoconazole(35 mg·kg-1), significantly increased the degree of liver injury(compared with LPS + trans-SG group, P < 0.05). The phase I metabolites of trans-SG were not detected in human liver microsomes phase I metabolism system, while the phase II trans-SG metabolites were detected in recombinant human UGT isozymes phase II metabolism system. Six isoforms of uridine diphosphate glucuronate transferase(UGT)exhibited abilities to metabolize trans-SG and the order of metabolic ability was: UGT1A1 > UGT1A9 > UGT1A7 > UGT1A10 > UGT2B7 > UGT1A8. The results showed that trans-SG was mainly metabolized by UGT in phase II metabolism. The inhibition of drug metabolizing enzymes of phase II can increase the liver injury susceptibility of trans-SG, which provides a reference to the evaluation of susceptible factors and drug incompatibility research of Polygonum multiflorum.

Glutathione S-transferase P1 Ile105Val Polymorphism and Male Infertility Risk: An Updated Meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Several studies concerning the association between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and male infertility risk have reported controversial findings. The present study was aimed to explore this association using a meta-analysis.</p><p><b>METHODS</b>The PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched. Odds ratios (OR s) with 95% confidence intervals (CI s) were calculated to estimate the strength of the association.</p><p><b>RESULTS</b>A total of 3282 cases and 3268 controls in nine case-control studies were included. There was no significant association between GSTP1 Ile105Val polymorphism and male infertility in the overall population, but significant associations were found under the dominant (OR = 1.23, 95% CI = 1.04-1.46, I2 = 32.2%) and heterozygote (OR = 1.29, 95% CI = 1.08-1.53, I2 = 26.8%) models after excluding studies for which the data did not satisfy Hardy-Weinberg equilibrium (HWE). Similarly, subgroup analyses revealed no significant association in Asians or Chinese population although a significant association was apparent among Chinese population in studies with HWE under the heterozygote model (OR = 1.25, 95% CI = 1.03-1.52, I2 = 44.1%). Significant heterogeneity could be observed in some genetic models, but this heterogeneity was not significant when stratified by HWE. No evidence for publication bias was found.</p><p><b>CONCLUSIONS</b>The GSTP1 Ile105Val polymorphism might not be associated with male infertility risk, and thus additional well-designed studies with larger sample size are warranted.</p>

Confocal Microscopy Evaluation of Meibomian Gland Dysfunction in Dry Eye Patients with Different Symptoms / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dry eye patients suffer from all kinds of symptoms. Sometimes, the clinical signs evaluation does not disclose any obvious difference in routine examination; in vivo confocal microscopy (IVCM) is a powerful tool for ocular surface disease. This study aimed to clarify meibomian gland (MG) alterations in dry eye patients with different symptoms and to compare the findings using IVCM.</p><p><b>METHODS</b>A total of sixty patients were recruited, all subjected to Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ), and questionnaires for the assessment of dry eye symptoms before clinical sign examinations were given to the patients. Finally, IVCM was applied to observe MG's structure. Statistical analysis was performed using the t-test, Mann-Whitney U-test and Spearman correlation analysis. The differences were statistically significant when P< 0.05.</p><p><b>RESULTS</b>In the severe symptom group, OSDI and SEEQ scores were significantly higher (P< 0.05) compared with the mild symptoms group. All other clinical sign examinations had no statistical difference in the two groups (P> 0.05). However, all the IVCM-observed data showed that patients with severe symptoms had more significant fibrosis in MG (acinar unit area 691.87 ± 182.01 μm2 for the severe, 992.17 ± 170.84 μm2 for the mild; P< 0.05) and severer decrease in the size of MG acinar units than those observed in patients with mild symptoms (MG acinar unit density [MGAUD] 70.08 ± 18.78 glands/mm2, MG acinar unit longest diameter [MGALD] 51.50 ± 15.51 μm, MG acinar unit shortest diameter [MGASD] 20.30 ± 11.85 μm for the severe, MGAUD 89.53 ± 39.88 glands/mm2, MGALD 81.57 ± 21.14 μm, MGASD 42.37 ± 14.55 μm for the mild;P< 0.05). Dry eye symptoms were negatively correlated with MG confocal microscopic parameters and positively correlated with conjunctival inflammatory cells and Langerhans cells (P< 0.05).</p><p><b>CONCLUSIONS</b>IVCM application provides a strong support to differentiate dry eye patients with different symptoms: meibomian gland dysfunction (MGD) plays a pivotal role in dry eye aggravation, and using IVCM to observe MG fibrosis, changes in size and density of MG as well as status of inflammation cells can help not only correctly diagnose the type and severity of dry eye, but also possibly prognosticate in routine eye examination in the occurrence of MGD.</p>

Geinsten inhibits the proliferation of VCaP castration-resistant prostate cancer cells / 中华男科学杂志

<p><b>Objective</b>To explore the inhibitory effect of genistein (GEN) on the proliferation of VCaP castration-resistant prostate cancer (CRPC) cells.</p><p><b>METHODS</b>VCaP CRPC cells were treated with GEN at the concentrations of 0, 12.5, 25, 50, 100, and 200 μmol/L for 24, 48, and 72 hours followed by determination of their proliferation by CCK-8 assay and their cycle by flow cytometry. The expression of Ki-67 in the cells was detected by immunocytochemistry and the levels of PSA, Cyclin D1, PCNA, and P53 determined by Western blot.</p><p><b>RESULTS</b>After 72 hours of treatment with GEN at 12.5, 25, 50, 100, and 200 μmol/L, the inhibition rates of the VCaP cells were (25.38±0.02)%, (31.14±0.29)%, (45.27±0.03)%, (52.19±0.05)%, and (68.21±0.19)%, respectively, all significantly higher than in the 0 μmol/L group (［10.08±0.02］%)(P<0.05). GEN caused the arrest of the VCaP cells in the G2/M phase (P<0.05) and inhibited the expression of Ki-67. The expressions of PSA, Cyclin D1, and PCNA were gradually down-regulated while that of P53 up-regulated with the increased concentration of GEN (P<0.05).</p><p><b>CONCLUSIONS</b>GEN inhibits the proliferation of VCaP CRPC cells by arresting the cell cycle with related protein expression changes.</p>