Induction of apoptosis in triple-negative breast cancer cells by petroleum ether extract of Sageretia thea / 药学实践与服务

Objective To investigate the effect of the petroleum ether extract of Sageretia thea on the proliferation and apoptosis of breast cancer cells. Methods After breast cancer cells were incubated with the petroleum ether extract for different times, cell viability was analyzed by CCK8 assay, cell proliferation was detected by plate cloning test, nuclear morphology was observed by DAPI staining, mitochondrial membrane potential（MMP）and reactive oxygen species（ROS）were determined by immunofluorescence, and the cell cycle and apoptosis were detected by flow cytometry. After incubating with the extract for 24 h, the CCK8 assay was used to observe the toxicity to normal human vascular endothelial cells. Results The IC50 of BT549 and MDA-MB-231 breast cancer cell lines treated with the petroleum ether extract for 24 h were 45.40 μg/ml and 12.23 μg/ml, respectively. The extract time and dose dependently inhibited breast cancer cell viability and clonal formation, induced cell apoptosis and cycle arrest in G1/S phase, decreased MMP and increased ROS levels. There was no toxic effect on normal endothelial cells. Conclusion The petroleum ether extract of Sageretia thea may induce apoptosis by increasing ROS to cause MMP collapse, followed by activating mitochondrial pathway, thereby hindering the growth of breast cancer cells. These results could support the application of Sageretia thea to anti-breast tumor in the folk.

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The main protease (Mpro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent Mpro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent Mpro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent Mpro inhibitors with desirable properties have been developed based on available crystal structures of Mpro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent Mpro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent Mpro inhibitors are also discussed.

Screening methods of SARS-CoV-2 main protease inhibitors and current applications / 药学学报

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (Mpro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 Mpro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 Mpro inhibitors.

Clinicopathological and molecular features of metaplastic thymoma / 中华病理学杂志

Objective: To investigate the clinicopathological features, and molecular genetic alterations of metaplastic thymoma (MT). Methods: A total of ten MT cases, diagnosed from 2011 to 2021, were selected from the Department of Pathology of Jinling Hospital, Nanjing University Medical School, Nanjing, China for clinicopathological and immunohistochemical (IHC) examination and clinical follow-up. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and YAP1 C-terminus (YAP1-CT) IHC were performed to detect YAP1::MAML2 fusions. Results: There were four males and six females, ranging in age from 29 to 60 years (mean 50 years, median 54 years). Microscopically, all tumors showed a typical biphasic morphology consisting of epithelial components and gradually or abruptly transitioning spindle cell components. The two components were present in varying proportions in different cases. Immunophenotypically, the epithelial cells were diffusely positive for CKpan, CK5/6 and p63. The spindle cells were diffusely positive for vimentin and focally positive for EMA. TdT was negative in the background lymphocytes. Ki-67 proliferation index was less than 5%. YAP1 and MAML2 break-apart FISH analyses showed that all ten cases had narrow split signals with a distance of nearly 2 signal diameters and may be considered false-negative. Using YAP1::MAML2 fusion FISH assays, abnormal fusion signals were observed in all the ten cases. NGS demonstrated YAP1::MAML2 fusions in all eight cases with adequate nucleic acids; in two cases the fusions were detected by DNA sequencing and in eight cases by RNA sequencing. All ten cases of MT demonstrated loss of YAP1 C-terminal expression in epithelioid cells. Conclusions: MT is a rare and low-grade thymic tumor characterized by a biphasic pattern and YAP1::MAML2 fusions. Break-apart FISH assays may sometimes show false-negative results due to the proximity of YAP1 and MAML2, while YAP1 C-terminal IHC is a highly sensitive and specific marker for MT. Loss of YAP1 C-terminal expression can also be used to screen YAP1::MAML2 fusions for possible MT cases.

Research progress of SARS-CoV-2 main protease inhibitors / 药学学报

As a common protease with high similarity among coronavirus species, the main protease (Mpro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

Discovery of novel sulfonamide substituted indolylarylsulfones as potent HIV-1 inhibitors with better safety profiles

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R10L4 was endowed with significant inhibitory activity towards wild-type HIV-1 (EC50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC50 = 0.017 μmol/L, SI = 13,055), E138K (EC50 = 0.017 μmol/L, SI = 13,123) and Y181C (EC50 = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R10L4 was characterized with significantly reduced cytotoxicity (CC50 = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R10L4 and HIV-1 RT. Additionally, R10L4 presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Papillary renal neoplasm with reverse polarity: a clinicopathological analysis / 中华病理学杂志

Objective: To study the clinical pathological characteristics, immunophenotype, molecular changes and prognosis of the papillary renal neoplasm with reverse polarity (PRNRP). Methods: Nine cases of PRNRP, diagnosed from 2013 to 2019, were retrieved from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histomorphology, immunophenotype and molecular genetics were analyzed with review of the literatures. Results: There were five male and four female patients, aged from 49 to 70 years, with an average age of 60.1 years. During a mean follow-up of 29 months, one patient died for other cause, and the others survived without disease. Microscopically, the tumor cells arranged in papillary structure with a fibrovascular core, the surface of which was covered with a single layer of cuboidal or columnar cells. The most prominent feature was that the tumor nuclei located at the top of the cytoplasm far from the basement membrane, and they were monotonous in size and arranged neatly with no or few nucleoli. Immunohistochemically, all nine cases of PRNRP showed diffuse positive expression of CK7 and E-cadherin, various degrees of P504s expression, and no expression of CD10 and CD117, with a Ki-67 index of 1%-3%. Unlike other papillary renal cell carcinoma, the nine cases of PRNRP all showed characteristic positive expression of GATA3. The fluorescence in situ hybridization assay showed that the majority of PRNRPs (8/9) did not have triploids on chromosomes 7 and 17. The sequencing of the KRAS gene confirmed the presence of a nonsense KRAS mutation in 8 of the 9 cases. Conclusions: PRNRP is a subtype of papillary renal cell carcinoma with characteristic morphological, immunophenotypic and molecular features, and indolent behaviors. More data are needed to define PRNRP as "carcinoma", and a definitive diagnosis of PRNRP is of great significance for proper treatment choice and accurate prognostication.

Semiquantitative parameters of 18F-FDG PET/CT, gene mutation states of epidermal growth factor receptor and anaplastic lymphoma kinase in prognosis evaluation of patients with lung adenocarcinoma / 北京大学学报(医学版)

OBJECTIVE@#To explore the valuable predictors for evaluating progression-free survival (PFS) in patients with lung adenocarcinoma, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from 18F-FDG PET/CT, combining with the gene mutation states of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and other clinical characteristics.@*METHODS@#Data of 84 lung adenocarcinoma patients pre-treated, who underwent 18F-FDG PET/CT scans, EGFR gene mutations test, ALK rearrangement assay and other relative tests, were retrospectively collected. Then a series of clinical parameters including EGFR/ALK mutation status and SUV-derived features [maximum standardized uptake value (SUVmax), average of standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were evaluated. Best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Survival analysis was performed using Cox proportional hazards model to determine the prognostic markers for progression-free survival (PFS). Survival curves were obtained through Log-rank test and Kaplan-Meier curve.@*RESULTS@#The median follow-up period was 31 months (24 to 58 months). It was found that SUVmax (≥3.01), SUVmean (≥2.25), MTV (≥25.41 cm3), and TLG (≥55.02) of the primary tumors were significantly associated with PFS in univariate Cox proportional hazards regression. Then regardless of age, gender, co-morbidity, EGFR/ALK mutation status, and treatment program, TLG (≥ 55.02, HR=4.965, 95%CI: 1.360-18.133), TNM stage (Ⅲ/Ⅳ, HR=7.811, 95%CI: 2.977-20.489), pro-gastrin releasing peptide (proGRP) (≥45.65 ng/L, HR=4.070, 95%CI: 1.442-11.487), tissue polypeptide antigen (TPA) (≥68.20 U/L, HR=6.996, 95%CI: 1.458-33.574), alkaline phosphatase (ALP) (≥82.50 IU/L, HR=4.160, 95%CI: 1.416-12.219) and ratio of activated partial thromboplastin time (aPTTR) (≥1.16: HR=4.58, 95%CI: 1.913-10.946) showed the independently relevant to PFS through multivariate Cox proportional hazards analysis. The EGFR mutant (P=0.343) and ALK rearrangement (P=0.608) were not significant either in survival analysis.@*CONCLUSION@#High SUV-derived parameters (SUVmax, SUVmean, MTV and TLG) might provide prognostic value to some extent. Especially, TLG, and other clinical features [TNM stage, proGRP, TPA, ALP, and aPTTR] could be independently and significantly associated with PFS of lung adenocarcinoma patients. However, EGFR/ALK gene status could not be effectively relevant to PFS in lung adenocarcinoma patients.

Association Between Organic Dust Exposure and Adult-Asthma: A Systematic Review and Meta-Analysis of Case-Control Studies

BACKGROUND: Exposure to organic dust has been widely investigated as a potential risk factor for asthma with different results. To clarify a potential relationship, we performed the present meta-analysis to integrate the results of studies examining the association of organic dust exposure with asthma. METHODS: A comprehensive literature search in the electronic databases including EMBASE, PubMed and Cochrane Library databases (up to August 2018) was conducted. The adjusted odds ratios (ORs) with corresponding 95% confidence interval (CI) for organic dust exposure and asthma were retrieved and pooled to generate summary effect estimates in Revman 5.2. RESULTS: Database searches retrieved 1,016 records. A total of 17 studies containing 3,619 cases and 6,585 controls were finally included in our meta-analysis. The summary estimates suggested that organic dust exposure was positively associated with asthma (OR, 1.48; 95% CI, 1.26–1.75; P < 0.00001), whether among population-based case-control studies (OR, 1.24; 95% CI, 1.13–1.35; P < 0.00001) or hospital-based case-control studies (OR, 2.79; 95% CI, 1.27–6.12; P = 0.01). Subgroup analysis showed that paper/wood (OR, 1.62; 95% CI, 1.38–1.90; P < 0.00001), flour/grain (OR, 1.48; 95% CI, 1.11–1.97; P = 0.008), and textile dust (OR, 1.50; 95% CI, 1.08–2.09; P = 0.02) exposure were significantly associated with asthma. CONCLUSIONS: Based on the studies evaluated, our meta-analysis results prompt that organic dust exposure is a risk factor inducing asthma, although precise analysis focus on specific organic dust materials is still warranted.

Primary testicular diffuse large B-cell lymphoma: A clinicopathological analysis / 中华男科学杂志

Objective@#To investigate the clinicopathological features, immunophenotype and treatment of primary testicular diffuse large B-cell lymphoma (DLBCL).@*METHODS@#We retrospectively analyzed the pathomorphological characteristics and immunohistochemical markers of 23 cases of primary testicular DLBCL as well as their clinicopathological features with a review of the relevant literature. The patients were aged 48－76 (mean 61.4) years, 82.6% over 50 years, and all clinically presented with painless progressive unilateral testicular swelling, 9 cases in the left and the other 14 in the right testis.@*RESULTS@#Histologically, the lymphomas were composed of large atypical cells with prominent karyokinesis and diffusely infiltrated the testicular parenchyma. The neoplastic cells were positive for B-cell markers. Five of the patients were followed up for 2 to 32 months, of whom 4 survived and 1 died at 9 months.@*CONCLUSIONS@#Primary testicular DLBCL is a rare tumor with an invasive biological behavior, mostly found in elderly males and easily misdiagnosed or missed in diagnosis. Histopathology plays a key role and immunohistochemical markers are of high value in the definite diagnosis and differential diagnosis of the tumor.

DNA re-use after immunohistochemical staining of FFPE sections of non-small cell lung cancer / 医学研究生学报

Objective　The purpose of this study was to evaluate the quality of DNA from the formalin-fixed paraffin-embedded (FFPE) specimens of non-small cell lung cancer (NSCLC) after immunohistochemical staining and investigate DNA extraction by immunohistochemical staining of the specimens in small in number or difficult to obtain and the feasibility of related molecular tests.　Methods　We randomly collected 50 FFPE biopsy specimens of NSCLC in our Department of Pathology from June 2017 to December 2017 and sliced each into 12 sections, of which, 6 were directly subjected to DNA extraction (the control group) and the other 6 to immunohistochemical Envision two-step staining for DNA extraction (the experimental group). Then, we detected the mutations of the epidermal growth factor receptor (EGFR), kirsten rat sarcoma viral oncogene (KRAS) and V-raf murine sarcoma viral oncogene homolog B (BRAF) in all the DNAs extracted.　Results　No statistically significant differences were observed between the experimental and control groups in the DNA concentration and purity in the 50 FFPE biopsy specimens of NSCLC (P>0.05). Of the 50 NSCLC FFPE specimens of the experimental group, 20 (40%) showed the mutation of EGFR, 8 (16%) exhibited that of KRAS, and 5 (10%) manifested that of BRAF. In the other 50 specimens of the control group, 33 showed the mutations of EGFR, KRAS and BRAF. A 100% consistency was found in the results of detection between the experimental and control groups (P=0.000, Kappa=1.000).　Conclusion　 High-quality DNA can be extracted after immunohistochemical staining from NSCLC FFPE specimens, especially those small in number or difficult to obtain, and can be used for downstream molecular analysis of target genes, which is a good method for specimen recycling and provides a solution for subsequent molecular test of scarce or difficult-to-obtain clinical samples.

Endoplasmic Reticulum Stress Induces the Early Appearance of Pro-apoptotic and Anti-apoptotic Proteins in Neurons of Five Familial Alzheimer's Disease Mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Amyloid β (Aβ) deposits and the endoplasmic reticulum stress (ERS) are both well established in the development and progression of Alzheimer's disease (AD). However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated.</p><p><b>METHODS</b>The five familial AD (5×FAD) mice and wild-type (WT) mice aged 2, 7, and 12 months were used in the present study. Morris water maze test was used to evaluate their cognitive performance. Immunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic (CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12) and anti-apoptotic factors (chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN1]) in the ERS-associated unfolded protein response (UPR) pathway.</p><p><b>RESULTS</b>Compared with age-matched WT mice, 5×FAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months (all P < 0.05). Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN1, were significantly increased when compared with those in age-matched WT mice (all P < 0.05). Moreover, ERS occurred mainly in neurons, not in astrocytes.</p><p><b>CONCLUSIONS</b>These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.</p>

Identification of a metal ion-induced degradation impurity in huperzine A injection / 中国药学杂志

OBJECTIVE: To identify the structure of an impurity of huperzine A injection. METHODS: HPLC-QTOF-MS was adopted to analyze the structure of the impurity, which was further isolated and prepared by prep-HPLC and the structure was established on the basis of spectroscopic data. RESULTS: The impurity was elucidated as (111E)-7,8-dichloro-5-amino-11-ethylidene-7-methyl-5,8,9,10-tetrahydro-5,9-methenecyclooctatriene [b] pyridin-2(1H)-one. CONCLUSION: The impurity was deduced as a metal ion-induced degradation product. This investigation provides reference for the improvement of quality control and process optimization of huperzine A injection.

Postoperative recurrence of multifocal papillary thyroid microcarcinoma and related factors analysis / 中华内分泌外科杂志

Objective To investigate the risk factors related with the recurrence of multifocal papillary thyroid microcarcinoma(PTMC).Methods The data of 126 patients undergoing surgery from Jan.2001 to Jun.2011 proved to be multifocal PTMC by pathology were rctrospcctively analyzed.Logistic multifactor regression analysis was used to analyze the clinicopathological factors that may influence the recurrence of PTMC.Results The median age of the 126 patients was 46 years(ranging from 15 to 78 years old).The recurrence rate was 14.3％ (18/126) and the overall survival rate was 98.4％ with the medium follow-up of 75 months (ranging from 24 to 150 months).Multivariate analysis showed that extra-thyoidal extension,neck lymph node metastasis and non-total(or near total)thyroidectomy were the independent risk factors for the recurrence of multifocal PTMC (P =0.008,0.027,0.022 respectively).Conclusions Extension beyond the thyroid and metastatic neck lymph node predict a high risk of recurrence.Total or near total thyroidectomy can reduce the risk of recurrence.

Consciousness and abilities on health emergency and the roles of emergency response among public at the communities / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the consciousness of health emergency and the abilities on self- and mutual medical aids among the public at the community level, as well as the community responses on health-related emergencies and other factors.</p><p><b>METHODS</b>Random equidistant sampling method was used to extract 617 households before choosing a family member sampled by Kish Grid method. All the members were investigated face to face on a questionnaire-"Health emergency and related ability regarding self and mutual medical aids of the residents". Data were entered into computer database by using software Epi Data 3.1 and were analyzed by SPSS 21.0.</p><p><b>RESULTS</b>Among the 617 households under survey, 47.84% of the public had general awareness on health-related emergencies. Regarding the following items as:prevention and isolation strategies of infectious disease, on safely procedures of earthquake and fires, on prevention of food poisoning, on prevention and first aid of emerging infectious diseases etc., the rates of awareness were 65.04%, 62.92%, 43.62% and 18.79% respectively. Proportions of households which had the first aid supplies were:first aid medicine box as 56.08%; fire extinguisher as 43.60%; spare water and food as 39.40%; having facilities as ropes, whistles and smoke masks for escape were all less than 15%. Rates of awareness on the following items as: correct use of gas switch as 81.52%, knowing the location of the circuit with gear and the fire hydrant as 74.39% and 35.98% , respectively. The correct disposal rates of the residents on the following items were:electric shock and falls (89.63%), patients of infectious diseases (83.31%), gas poisoning (82.98%), suspected symptoms on infectious diseases(82.66%), explosion and burns (66.78%), scald (62.72%)and sprain (57.05%). Scores on the related abilities were as follows: emergency(7.65, out of 10 points), escape(3.55, out of 5 points), self- and mutual medical aids (10.71, out of 16 points). Proportions of having learned and applied of first aid techniques among residents on the following items were:artificial breathing, chest compressions and cardiopulmonary resuscitation were all less than 10%. Level of knowing the first aid techniques was correlated with age and culture of the residents (P < 0.05).</p><p><b>CONCLUSION</b>Both consciousness on health emergency and the abilities on self- and mutual medical aids were low among the community public, suggesting that both the government and pubic should pay more attention to the role of the abilities on self- and mutual medical aids.</p>

Value of virtual touch tissue quantification technique in the diagnosis of small solid thyroid nodules / 中华超声影像学杂志

Objective To explore the application value of virtual touch tissue quantification(VTQ) technique in differentiating small solid thyroid nodules.Methods The patients with suspiciously malignant thyroid nodules(solitary,size range 5-15 mm),homogeneous and normal color Doppler flow imaging in the rest of thyroid parenchyma,were enrolled in this study.Five repeated measurements were performed on both nodules and extra-nodular tissues using VTQ.A receiver-operating characteristic (ROC) curve was drew according to shear wave velocity(Vs).Results 62 patients with a total of 67 lesions were included in this study,turned out to be 39 malignant and 28 benign.The Vs of malignant group nodules,malignant group extra-nodular tissues,benign group nodules and benign group extra-nodular tissues were (3.91 ±1.85) m/s,(2.03 ± 0.42)m/s,(2.29 ± 0.56)m/s,(1.84 ± 0.45)m/s,respectively.The Vs difference between malignant and benign nodules was statistically significant (P =0.000),while the Vs difference between malignant and benign extra-nodular tissues had no statistical significance (P =0.07).The best cutoff Vs value for distinguishing malignant from benign nodules was 2.78 m/s,with the sensitivity,specificity and accuracy of 76.9％,78.6％ and 80.6％ respectively.The area under ROC curve was 0.84.Conclusions VTQ could evaluate the elasticity of thyroid nodules,and was helpful in the diagnostic work-up of thyroid nodules.

Investigation on the related prognostic factors of the patients with thyroid microcarrinoma / 中国基层医药

Objective To explore the related prognostic factors of the patients with thyroid microcarcinoma.Methods Clinical data,including clinical,pathologic,and therapeutic factor of 203 patients with thyroid microcarcinoma admitted were analyzed retrospectively.Results The cause specific survival and locoregional failure free survival rates at 10 years were 100.0% and 91.4% , respectively.Univariate analysis showed that multifocality, cervical lymph node metastasis and radioiodine treatment was associated with prognosis.Multivariate analysis revealed that cervical lymph node metastasis was the only independent prognostic factor for locoregional failure free survival.The risk of locoregional recurrence increased 2.5 folds when lymph nodes metastasis occurred at presentation.Conclusion The ratio of thyroid microcarcinoma to thyroid carcinoma increased yearly and the overall survival rate of thyroid microcarcinoma was excellent.Of all the prognostic factors,lymph node metastasis was the most important one related to survival.

Correlation analysis of cognitive function and changes in proton magnetic resonance spectroscopy of the hippocampus in patients with complex partial seizures / 中华神经医学杂志

Objective To investigate the features of cognitive impairment in patients with complex partial seizures (CPS) and the correlation between the cognitive function and proton magnetic resonance spectroscopy (~1H-MRS). Methods Forty-five patients with CPS and 16 healthy controls were examined by the following means: memory function examination by the clinical memory scale, intelligence function examination by Ravin's standard progressive Matrices (R'SPM) and ~1H-MRS scan in the bilateral hippocampus. Memory quotient (MQ), Intelligence quotient (IQ), the levels ofNAA, Cho, Cr and the ratio of NAA/Cr+Cho were compared between the two groups. Meanwhile, the correlation coefficients were calculated. Results The scores of pointing memory, associational learning, image free memory, association memory of portrait and MQ except insignificant figure recognition were significantly lower in patients with CPS than those in the control group (P<0.05); the scores of Ravin's standard progressive matrices and IQ were noticeably lower in patients with CPS than those in the controls. The levels of NAA, Cho, Cr and the ratio of NAA/Cr+Cho in patients with CPS were significantly lower than those in the controls (P<0.05). Patients with CPS showed positive correlation between MQ and the level ofNAA, MQ and the ratio ofNAA/Cr+Cho, IQ and the level of NAA, as well as IQ and the ratio ofNAA/Cr+Cho (P<0.05); while level of Cho and both MQ and IQ were in inverse proportion (P<0.05) and no correlation between the lever of Cr and both MQ and IQ was found in patients with CPS (P>0.05). Conclusions The patients with CPS do have the cognitive impairment including short-term memory deficit and the decreased ability of abstraction, maturity judgment and reasoning. The correlation between cognitive function and the levels ofNAA, Cho, Cr and the ratio of NAA/Cr+Cho indicated that ~1H-MRS can check the cognitive function of patients with CPS in early stage objectively. Together with neuropsychology examination, ~1H-MRS can detect the disturbance of cognitive function in the patients with CPS precisely in early stage.

Methylation status of DLEC1 promoter in colorectal cancer patients and its clinical relevance / 第二军医大学学报

Objective: To detect the methylation status of DLEC1 promoter in the tissue and serum of colorectal cancer (CRC) patients and to evaluate its clinical relevance. Methods: Genomic DNA was extracted from the tissues (cancer tissue and. corresponding adjacent normal tissue) and sera of 71 CRC patients; serum genomic DNA was also obtained from 20 patients with benign gastrointestinal diseases and 20 healthy donors. Promoter methylation status of DLEC1 gene was detected by methylation-specific polymerase chain reaction (MSP). Results: The incidence of aberrant methylation of DLEC1 promoter was 45.1% (32/71) in CRC tissues, which was significantly higher than that in the adjacent normal tissues (7.1%, 4/56) (P< 0.001). The hypermethylation status of DLEC1 was not correlated with the clinicopathological features and CEA/CA19-9 levels of CRC patients. Moreover, DLEC1 promoter methylation was also found in 28 of 71 (39. 4%) CRC serum samples and only 1 (2.5%) of the other 40 cancer-free serum samples (P<0.001); the methylation was in accordance with that in the tumor tissues. Conclusion: Hypermethylation of DLEC1 promoter is frequently seen in CRC patients, suggesting it might be a promising biomarker for the early diagnosis of CRC.

Effect of rosiglitazone on tumor necrosis factor-alpha-induced nuclear factor-kappaB and coupling factor 6 expressions in human umbilical vein endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of rosiglitazone on the expression of nuclear factor-kappaB (NF-kappaB) and coupling factor 6 (CF6) induced by tumor necrosis factor-alpha (TNF-alpha) in cultured human umbilical vein endothelial cells (HUVEC).</p><p><b>METHODS</b>Cultured HUVEC of passage 3-5 were stimulated with TNF-alpha and then cultured in the presence of rosiglitazone. The expression of CF6 and NF-kappaB subunit p65 were evaluated by immunocytochemistical method.</p><p><b>RESULTS</b>Pretreatment of HUVECs with rosiglitazone inhibited TNF-alpha-induced expression of CF6 in a dose-dependent manner. The activation of CF6 stimulated by TNF-alpha was suppressed by ROS in a dose-dependent manner.</p><p><b>CONCLUSION</b>TNF-alpha-induced enhancement of the gene expression and release of CF6 is mediated by activation of NF-kappaB signaling pathway. ROS can inhibit the activation of IKK, block NF-kappaB signaling pathway and inhibit the expression of CF6, which may be the mechanism underlying the action of TZDs on hypertension.</p>