Prognostic predictive value of Ki-67 in stage I-II triple-negative breast cancer.

Aim: Our research aimed to determine an optimal cutoff value and investigate the prognostic predictive function of Ki-67. Materials & methods: We retrospectively enrolled 1146 patients diagnosed with stage I-II triple-negative breast cancer. Disease-free and overall survival were analyzed using the Kaplan-Meier method and the Cox regression model. Results: We classified Ki-67 >45% as the high group (n = 716). A Ki-67 level of >45% was associated with poorer disease-free survival (p = 0.039) and overall survival (p = 0.029). Lymph node stage, neoadjuvant chemotherapy, and radiotherapy were independent predictive variables of prognosis. Conclusion: Triple-negative breast cancer may be further subcategorized according to the Ki-67 level. Neoadjuvant chemotherapy and postoperative radiotherapy can improve the prognosis of early triple-negative breast cancer.

This study aimed to find the best value of Ki-67, which is a marker used in breast cancer. At last, according to the Ki-67 level over 45%, triple-negative breast cancer may be divided into two groups. Based on the level of Ki-67, treatment decisions may be better. However, we still need more studies to confirm this.

Triple-negative breast cancer may be further subcategorized according to the Ki-67 level >45%, which is associated with a poorer prognosis. Treatment decisions based on the level of Ki-67 may be more favorable to the prognosis of patients.

Occurrence and genetic characterization of Enterocytozoon bieneusi in pet dogs in Yunnan Province, China.

Enterocytozoon bieneusi is the most common microsporidian species in humans and can affect over 200 animal species. Considering possible increasing risk of human E. bieneusi infection due to close contact with pet dogs and identification of zoonotic E. bieneusi genotypes, 589 fresh fecal specimens of pet dogs were collected from Yunnan Province, China to determine the occurrence of E. bieneusi, characterize dog-derived E. bieneusi isolates, and assess their zoonotic potential at the genotype level. Enterocytozoon bieneusi was identified and genotyped by PCR and sequencing of the internal transcribed spacer (ITS) region of the ribosomal RNA (rRNA) gene. Twenty-nine specimens (4.9%) were positive. A statistical difference was observed in occurrence rates of E. bieneusi in pet dogs among 11 sampling sites by Fisher's exact test. Fifteen genotypes were identified and all of them phylogenetically belonged to zoonotic group 1, including four known genotypes (EbpC, D, Peru 8, and Henan-III) and 11 novel genotypes. Genotype Henan-III was reported in dogs for the first time. The finding of known genotypes found previously in humans and novel genotypes falling into zoonotic group 1 indicates that dogs may play a role in the transmission of E. bieneusi to humans in the investigated areas.

Title: Occurrence et caractérisation génétique d'Enterocytozoon bieneusi chez les chiens de compagnie dans la province du Yunnan, Chine. Abstract: Enterocytozoon bieneusi est l'espèce de microsporidies la plus répandue chez l'homme et peut affecter plus de 200 espèces animales. Compte tenu du risque accru possible d'infection humaine à E. bieneusi en raison d'un contact étroit avec des chiens de compagnie et de l'identification de génotypes zoonotiques d'E. bieneusi, 589 échantillons fécaux frais de chiens de compagnie ont été collectés dans la province du Yunnan, en Chine, pour déterminer la présence d'E. bieneusi, caractériser les isolats obtenus de chiens, et évaluer leur potentiel zoonotique au niveau du génotype. Enterocytozoon bieneusi a été identifié et génotypé par PCR et séquençage de la région d'espacement transcrit interne (ITS) du gène de l'ARN ribosomal (ARNr). Vingt-neuf échantillons (4,9%) étaient positifs. Une différence statistique a été observée dans les taux de présence d'E. bieneusi chez les chiens de compagnie parmi 11 sites d'échantillonnage par le test exact de Fisher. Quinze génotypes ont été identifiés et tous appartenaient phylogénétiquement au groupe zoonotique 1, dont quatre génotypes connus (EbpC, D, Peru 8 et Henan-III) et 11 nouveaux génotypes. Le génotype Henan-III est signalé pour la première fois chez le chien. La découverte de génotypes connus précédemment trouvés chez l'homme et de nouveaux génotypes appartenant au groupe zoonotique 1 indique que les chiens peuvent jouer un rôle dans la transmission d'E. bieneusi aux humains dans les zones étudiées.

Treatments and Prognosis of the Breast Ductal Carcinoma In Situ.

INTRODUCTION: With progress in treatments, breast ductal carcinoma in situ (DCIS) outcomes have substantially improved. However, as various treatment methods are used in different countries and institutions, consensus on the optimal treatment method is lacking. This study aimed to analyze the prognostic factors and provide a reference for optimizing the clinical treatment of DCIS. PATIENTS AND METHODS: This retrospective clinical study collected data from DCIS patients at the Sun Yat-sen University Cancer Center from 2010 to 2017. The Kaplan-Meier method and Cox regression model were used to assess disease-free survival (DFS), overall survival (OS), and local control (LC) rates. RESULTS: Among the 483 included patients, 83.6% (404) underwent mastectomies. The median follow-up time was 101 months. The number of patients undergoing breast-conserving surgery (BCS) with radiotherapy has gradually increased. Axillary lymph node dissection was the main surgery performed from 2010 to 2015, and the proportion of sentinel lymph node biopsies (SLNBs) has increased. LC and DFS rates with BCS without radiotherapy were significantly lower than those with mastectomy (P = .002; P < .001). Additionally, the patients who did not undergo axillary surgery had worse LC and OS rates than those who underwent SLNB (P = .028 and P = .038). Endocrine therapy (ET) or its duration had no significant effect on prognosis. CONCLUSION: In conclusion, BCS without radiotherapy and lack of axillary surgery were independent prognostic factors. We recommend performing BCS with radiotherapy and SLNB more in clinical practice, as well as shortening the ET duration.

Investigation of Hexagonal Mesoporous Silica-Supported Composites for Trace Moisture Adsorption.

Moisture control is an important part of effective maintenance program for gas-insulated switchgear (GIS). Herein, hexagonal mesoporous silica (HMS) materials were synthesized by adopting dodecylamine as a structure directing agent, which was then employed as a host for supporting polyethylenimine (PEI) without further calcinations or extraction treatment. The physicochemical properties of the silica support and composites were characterized, and the moisture adsorption capacity of these composites was determined. The reserved template agents resulted in a dramatic improvement in moisture adsorption amount. Among them, 50PEI/DHMS showed the highest adsorption value. The enhanced adsorption could be attributed to the generated hydrogen bonding between amino groups and H2O molecules and the improved diffusion of moisture into the bulk networks of PEI polymers due to its better spatial dispersion imposed by the long alkyl chains of template agents, which was confirmed by thermogravimetry results and hydrogen efficiency analysis. Moreover, the maintained terminal amino groups of templates could also function as active sites for moisture adsorption. The results herein imply that the PEI/DHMS composites could be appealing materials for capturing moisture in GIS.

Investigation by MD simulation of the key residues related to substrate-binding and heme-release in human ferrochelatase.

Molecular dynamics (MD) simulations of three models based on the crystal structure of the E343K variant of human ferrochelatase were performed in this study. The "open" and "closed" conformations of the enzyme obtained by simulations are in agreement with the corresponding crystal structures. The snapshots and the structure analysis indicate that alterations of the hydrogen bonds and the positions of E347 and E351 lead to a conformational change in the π-helix. The hydrogen bonded form of residue R164 could be regarded as a signal indicating alteration of the active site conformation. When R164 forms a hydrogen bond with D95, the active site is closed, and when a hydrogen bond is formed with E171, the active site is open. Interestingly, the protoporphyrin with Fe(2+) is observed to move noticeably out of the enzyme while the protoporphyrin lacking Fe(2+) remains almost fixed. Alterations of the hydrogen bonds between the propionate of the heme and R115, K118 and S303 trigger movement of the heme out of the active site. Residues E347 and E351, which are located on the π-helix and form an acidic path leading to a salt bridge interaction with the propionate of the heme, accelerate the release process.

Is it possible for Fe2+ to approach protoporphyrin IX from the side of Tyr-13 in Bacillus subtilis ferrochelatase? An answer from QM/MM study.

We previously reported the insertion process of the ferrous ion into the protoporphyrin IX from the side of the residue His-183 (J. Inorg. Biochem. 103 (2009) 1680-1686). Sellers et al. suggested that the ferrous ion probably approaches the protoporphyrin IX via the opposite side in the human enzyme. In this paper, we simulated the insertion process of Fe(2+) into the protoporphyrin IX from the side of the residue Tyr-13 at the opposite site of His-183 by QM/MM method on Bacillus subtilis ferrochelatase. The model was built with Fe(2+) ion coordinated by Tyr-13, His-88 and two water molecules. Geometries were optimized at the BP86/6-31G* level and energies were calculated at the B3LYP/6-311+G(2d,2p) level. The overall process involves the displacement of the residues Tyr-13, His-88 and one water molecule and deprotonation of the porphyrin ring. All the local minimum structures and energy barriers were obtained and an optimal insertion pathway was suggested. The rate-determining step is the removing of the second proton from the porphyrin accompanied by the formation of the fourth Fe-N bond with an energy barrier of 138.00 kJ/mol.

QM/MM study of the insertion of metal ion into protoporphyrin IX by ferrochelatase.

Ferrochelatase catalyzes the metallation of protoporphyrin IX in the terminal step of heme biosynthesis. Mutations in the ferrochelatase gene can lead to the disease erythropoietic porphyria. The catalyzing mechanism of ferrochelatase is still not fully understood. In this paper, we have studied the insertion of Fe(2+) into the protoporphyrin IX ring by Bacillussubtilis ferrochelatase using combined quantum mechanical and molecular mechanics (QM/MM) calculations. Geometries were optimized at the BP86/6-31G * level and energies were calculated at the B3LYP/TZVP level. The overall process involves the stepwise displacement of Glu-264, His-183, and a water molecule from Fe(2+), and the removal of two protons from the porphyrin ring. The rate-determining step is the cleavage of the bond between the oxygen atom of Glu-264 and Fe(2+), concomitant with the formation of the first Fe-N bond. It has an energy barrier of 57 kJ mol(-1). The porphyrin ring is only slightly distorted in the enzyme active site. The residue Tyr-13 plays a key role for the catalytic process extracting two protons from protoporphyrin IX.