OBJECTIVE Glioblastoma multiforme (GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis. No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de-veloping new agents to treat GBM is important. This study aimed to evaluate the anti-tumor effect of evodiamine (Evo) on GBM cells, and to determine the underlying mechanisms involved. METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and 48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo-diamine(0-10 μmol·L-1)for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species(ROS)production was detected using dichlorofluorescein diacetate (DCFH-DA) staining. The changes in mitochondrial mem-brane potential (MMP) were assessed by JC-1 after cells were treated with evodiamine. The expres-sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c, Caspase-3, cleaved Caspase-3, PRAP, and cleaved PARP were measured by Western blot analy-ses. RESULTS According to MTT assay results, Evo significantly inhibited the cell proliferation in a time- and dose-dependent manner. Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disruption. Finally, Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos-phorylation(p38 and JNK,but not ERK)to regulate apoptotic proteins(Bax,Bcl-2,Cytochrome c,Cas-pase-3, and PARP). CONCLUSION In summary, Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.

1,2,3,4,6-penta-O-galloyl-D-glucose (PGG) is one of the main active compounds of Guizhi Fuling capsule. Molecularly imprinted polymers (MIP) have high affinity toward template molecules synthesized by molecularly imprinted technology for its specific combined sites, which can overcome the shortcoming of traditional separation methods, such as complex operation, low efficiency, using large quantity of solvent and environmental pollution. In this paper, surface molecularly imprinted polymer (SMIP) was prepared by surface imprinting with PGG as the template molecule. Its adsorption capacity was measured by the scatchard equation. The separation of PGG from Guizhi Fuling capsule at preparatived scale was achieved with molecularly imprinted polymer as stationary phase and the purity was 90.2% by HPLC. This method can be used to prepare PGG from Guizhi Fuling capsule with large capacity and is easy to operate. It provides a new method for efficient separation and purification for other natural products.
Adsorption ; Capsules ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Hydrolyzable Tannins ; chemistry ; isolation & purification ; Molecular Imprinting ; Polymers ; chemical synthesis ; chemistry

Background Keratoconus is a bilateral,noninflammatory,gradually progressive corneal disorder characterized by progressive thinning and steepening of the central cornea.It is significant to investigate keratoconusrelated pathogenic gene for elaborating the pathogenesis and establishing early diagnosis standard and taking clinical measurement.Objective The aim of the study was to explore the relationship of visual system homeobox gene (VSX1) polymorphism and the risk of sporadic keratoconus.Methods This study was approved by Ethic Commission of First Hospital of Xi' an.Written informed consent was obtained from each subject prior to enrollment.A case-controlled study was conducted.One hundred and one Han nationality patients with sporadic keratoconus were included in this study.These keratoconus patients were clinically diagnosed by slit lamp examination and corneal tomography.Single nucleolide polymorphism (SNP) of VSX1 gene was assayed and classified using the MassARRAY SNP technique.Demography and relevant risk factors were collected from each subject by questionnaire.Eighty healthy volunteers served as controls.Chi-square test and Binary logistic regression were used to evaluate the difference in the distribution of allele frequency and genotype frequency and to analyze the association with keratoconus risks.Results SNP of two genes was found in the Chinese Han population (rs743018 (c.843+140 C＞T) and rs6138482(R217H C＞T)).There were no significant differences in the genotype frequency and allele frequency of the SNP of two genes in the keratoconus group in comparison with the normal control group (P＞0.05).After adjustment by age and sex,SNP of two genes was not significantly associated with the risk of keratoconus (regression model:rs743018 (C＞T) adjusted:P=0.35,OR=0.72,95％ CI:0.37-1.43 ;rs6138482 (C＞T) adjusted:P =0.48,OR=0.76,95％ CI:0.35-1.64).Conclusions Gene polymorphisms of rs743018(c.843+140 C＞T) and rs6138482(R217H C＞T) in the Chinese Han population is not associated with the risk of keratoconus.Due to the racial difference in genotype and allele frequency,the role of the VSX1 gene in the pathogenesis of keratoconus still remains controversial,and further study needs to be developed.

OBJECTIVETo study the anti-complementary phenolic acids from Lonicera japonica.

METHODThe anti-complementary activity-directed isolation was carried out with the hemolysis test as guide. All isolation was evaluated for their in vitro anti-complementary activities. The structures were identified by various spectroscopic data including ESI-MS, 1H-NMR, 13C-NMR data.

RESULTFourteen compounds were isolated from the EtOAc fraction of L. japonica extracts, including 8 phenolic acids: 5-O-caffeoylquinic acid (1), chlorogenic (2), 4-O-caffeoylquinic acid (3), 3,5-di-O-caffeoylquinic acid (4), 4,5-di-O-caffeoylquinic acid (5), 3,4-di-O-caffeoylquinic acid (6), caffeic acid (7) and methyl caffeate acid (8); 3 iridoids: secologanoside (9), sweroside (10) and secoxyloganin (11); and 3 flavonoids: luteolin (12), quercetin (13) and kaempferol (14). Compounds 1-9 and 11-14 showed anti-complementary activity in different extents and 3,5-di-O-caffeoylquinic acid (4) exhibited the most significant activity against the classical pathway.

CONCLUSIONCompound 14 is obtained from this plant for the first time, phenolic acids are the main anti-complementary constituents of L. japonica and 3,5-di-O-caffeoylquinic acid(4) is a potential complement inhibitor with strong activity, which worthy to be studied further in the future.

Complement Inactivating Agents ; chemistry ; isolation & purification ; pharmacology ; Hydroxybenzoates ; chemistry ; isolation & purification ; pharmacology ; Lonicera ; chemistry

The development of a RF ablation therapeutic instrument based on improved PID algorithm is introduced here. It is based on the theory of radio frequency local destruction. By adopting the improved PID temperature control algorithm, the problem of the temperature control precision reduction due to tumor tissue characteristic changing by heating has been solved, thus ensuring homogeneous and smooth radio frequency heating to tumor foci. Experiments demonstrate that the new algorithm has strong adaptability and anti-disturbance capability, the equipment works stably and reliably, and can control therapeutic temperature precisely (+/- 2 degrees C), which indicates a good clinical application value.
Algorithms ; Calorimetry ; instrumentation ; methods ; Catheter Ablation ; instrumentation ; methods ; Electrodes ; Equipment Design ; Humans ; Hyperthermia, Induced ; instrumentation ; methods ; Information Storage and Retrieval ; Neoplasms ; therapy ; Software ; Temperature

Objective: Patients with a history of ischemic stroke are at risk for a second ischemic stroke. This study aimed to investigate the relationship between carotid plaque enhancement on perfluorobutane microbubble contrast-enhanced ultrasonography (CEUS) and future recurrent stroke, and to determine whether plaque enhancement can contribute to risk assessment for recurrent stroke compared with the Essen Stroke Risk Score (ESRS). Materials and Methods: This prospective study screened 151 patients with recent ischemic stroke and carotid atherosclerotic plaques at our hospital between August 2020 and December 2020. A total of 149 eligible patients underwent carotid CEUS, and 130 patients who were followed up for 15–27 months or until stroke recurrence were analyzed. Plaque enhancement on CEUS was investigated as a possible risk factor for stroke recurrence and as a possible adjunct to ESRS. Results: During follow-up, 25 patients (19.2%) experienced recurrent stroke. Patients with plaque enhancement on CEUS had an increased risk of stroke recurrence events (22/73, 30.1%) compared to those without plaque enhancement (3/57, 5.3%), with an adjusted hazard ratio (HR) of 38.264 (95% confidence interval [CI]:14.975–97.767; P < 0.001) according to a multivariable Cox proportional hazards model analysis, indicating that the presence of carotid plaque enhancement was a significant independent predictor of recurrent stroke. When plaque enhancement was added to the ESRS, the HR for stroke recurrence in the high-risk group compared to that in the low-risk group (2.188; 95% CI, 0.025–3.388) was greater than that of the ESRS alone (1.706; 95% CI, 0.810–9.014). A net of 32.0% of the recurrence group was reclassified upward appropriately by the addition of plaque enhancement to the ESRS. Conclusion Carotid plaque enhancement was a significant and independent predictor of stroke recurrence in patients with ischemic stroke. Furthermore, the addition of plaque enhancement improved the risk stratification capability of the ESRS.

Objective: To investigate the multidetector computed tomography (MDCT) features of fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) with germline or somatic mutations, and compare them with those of papillary type II RCC (pRCC type II). Materials and Methods: A total of 24 patients (mean ± standard deviation, 40.4 ± 14.7 years) with pathologically confirmed FH-deficient RCC (15 with germline and 9 with somatic mutations) and 54 patients (58.6 ± 12.6 years) with pRCC type II were enrolled. The MDCT features were retrospectively reviewed and compared between the two entities and mutation subgroups, and were correlated with the clinicopathological findings. Results: All the lesions were unilateral and single. Compared with pRCC type II, FH-deficient RCC was more prevalent among younger patients (40.4 ± 14.7 vs. 58.6 ± 12.6, p < 0.001) and tended to be larger (8.1 ± 4.1 vs. 5.4 ± 3.2, p = 0.002). Cystic solid patterns were more common in FH-deficient RCC (20/24 vs. 16/54, p < 0.001), with 16 of the 20 (80.0%) cystic solid tumors having showed typical polycystic and thin smooth walls and/or septa, with an eccentric solid component. Lymph node (16/24 vs. 16/54, p = 0.003) and distant (11/24 vs. 3/54, p < 0.001) metastases were more frequent in FH-deficient RCC. FHdeficient RCC and pRCC type II showed similar attenuation in the unenhanced phase. The attenuation in the corticomedullary phase (CMP) (76.3% ± 25.0% vs. 60.2 ± 23.6, p = 0.008) and nephrographic phase (NP) (87.7 ± 20.5, vs. 71.2 ± 23.9, p = 0.004), absolute enhancement in CMP (39.0 ± 24.8 vs. 27.1 ± 22.7, p = 0.001) and NP (50.5 ± 20.5 vs. 38.2 ± 21.9, p = 0.001), and relative enhancement ratio to the renal cortex in CMP (0.35 ± 0.26 vs. 0.24 ± 0.19, p = 0.001) and NP (0.43 ± 0.24 vs. 0.29 ± 0.19, p < 0.001) were significantly higher in FH-deficient RCC. No significant difference was found between the FH germline and somatic mutation subgroups in any of the parameters. Conclusion The MDCT features of FH-deficient RCC were different from those of pRCC type II, whereas there was no statistical difference between the germline and somatic mutation subgroups. A kidney mass with a cystic solid pattern and metastatic tendency, especially in young patients, should be considered for FH-deficient RCC.

OBJECTIVETo investigate the effects of smoking on sperm apoptosis and semen quality of healthy adult males in the main urban area of Chongqing.

METHODSAccording to the smoking habit, we divided 235 healthy adult males into a non-smoking group (n = 89) and a smoking group (n = 146). Then we detected the routine semen parameters by the computer-assisted semen analysis system and obtained the parameters of sperm apoptosis (the ratios of AN-/PI-, AN+/PI-, AN+/PI+ and AN-/PI+ sperm) by flow cytometry combined with Annexin V-FITC/PI fluorescence staining.

RESULTSThe rate of early apoptotic sperm (AN+/PI-) was higher in the smoking than in the non-smoking group ([8.1 +/- 5.1]% vs [6.8 +/- 3.8]%; P = 0.039), but there were no significant differences between the two groups in the rate of late apoptotic sperm (AN+/PI+) ([5.6 +/- 5.2]% vs [5.5 +/- 5.1]%; P = 0.87), as well as in such routine semen indexes as semen volume, sperm density, sperm motility, sperm vitality and normal sperm morphology (P = 0.30, 0.82, 0.37, 0.81 and 0.84, respectively).

CONCLUSIONThe rate of early apoptotic sperm is higher in smokers than in non-smokers, suggesting that smoking may induce early damage to sperm cells. Compared with routine semen parameters, sperm apoptosis is a more sensitive biomarker to reflect smoking-induced damage to sperm.

Apoptosis ; China ; Humans ; Male ; Semen ; Semen Analysis ; Smoking ; Sperm Count ; Sperm Motility ; Spermatozoa ; cytology

Objective To study the effects of the serum Nesfatin-1 level change by type 2 diabetes in patients with Non-alcoholic fatty liver,and provides a reliable basis for its prysiological effects.Methods Selected 300 cases with type 2 diabetes mellitus in deoartment of endocrinology from January 2014 to January 2016 in Affiliated Hospital of Yan'an University as the object of this study.According to whether the patients were combined with non-alcoholic fatty liver,the patients were divided into T2DM with NAFLD group (150 cases) and T2DM without NAFLD group (150 cases).In addition,150 volunteers for healthy check-up in the hospital were selected as control group.Compared the serum Nesfatin-1 levels of three group patients,and monitored the insulin resistance index of two groups patients with type 2 diabetes.Results BMI,TG,ALT and INS of NGT(23.1±1.9,1.7±0.5,26.9±12.7 and 9.7±2.4,respectively) group and T2DM (22.1±2.5,2.0± 0.9,22.1 ± 10.5 and 11.2± 4.5,respectively) group were significantly lower than those of T2DM-NAFLD group (26.5 ± 3.8,3.0± 2.5,31.9 ± 11.5 and 14.2 ± 6.5;all P value were 0.00).FBG,HbAlc,LDL-C,HOMA-IR and Nesfatin-1 of T2DM group (8.4±3.1,8.8±2.7,3.4±1.0,4.5±2.9 and 6.9±3.0) and T2DM-NAFLD group (8.2±2.7,8.5± 1.9,3.7 ± 2.1,5.2 ± 2.7 and 5.2 ± 2.7) were significantly higher than those in serum NGT group (5.1 ± 0.5,5.4 ± 0.4,2.7 ±0.8,2.7±0.8 and 2.3± 0.7,all P value were 0.00).The serum Nesfatin-1 levels of T2DM patients and patients with T2DM-NAFLD had moderate correlation (r=-0.421,P＜0.05) by Pearson correlation analysis.BMI,TG and serum Nesfatin-1 levels were closely associated with the occurrence of fatty liver (r=-0.402 ～ 0.273;P=0.00 ～ 0.01).Conclusion Nesfatin-1 may be involved in type 2 diabetes mellitus and the occurrence of non-alcoholic fatty liver.

OBJECTIVETo validate the value of the Oxford classification of IgA nephropathy in predicting the renal outcome in Chinese population.

METHODSRetrospective study was done in patients with IgA nephropathy. All slides were re-assessed according to the Oxford classification of IgA nephropathy. The primary end point is doubling serum creatinine, or a 50% reduction in estimated glomerular filtration rate (eGFR), or end-stage renal disease. Pathologic predictors for the progression to the end point were determined by univariate and multivariate Cox regression.

RESULTSTotally 533 patients were enrolled in the study. During the follow-up (median: 39 months; range: 12-263 months), 5.07% of the patients reached the end point. While tubular atrophy and interstitial fibrosis and arterial/ arteriolar lesion were associated with the endpoint in univariate analysis, only the T score was predictive of the renal outcome in multivariate Cox regression. Combination of the patho- logic lesions had no impact on renal outcome.

CONCLUSIONAccording to the Oxford classification of IgA nephropathy, the degree of tubulointerstitial fibrosis is the only feature independently predictive of renal outcome.

Adolescent ; Adult ; Aged ; Female ; Follow-Up Studies ; Glomerulonephritis, IGA ; classification ; pathology ; Humans ; Kidney ; pathology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Young Adult