Methylmercury induces inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasome.

Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood-brain barrier and cause irreversible damage to the human central nervous system (CNS). CNS inflammation and autophagy are known to be involved in the pathology of neurodegenerative diseases. Meanwhile, MeHg has the potential to induce microglia-mediated neuroinflammation as well as autophagy. This study aims to further explore the exact molecular mechanism of MeHg neurotoxicity. We conducted in vitro studies using BV2 microglial cell from the central nervous system of mice. The role of inflammation and autophagy in the damage of BV2 cells induced by MeHg was determined by detecting cell viability, cell morphology and structure, reactive oxygen species (ROS), antioxidant function, inflammatory factors, autophagosomes, inflammation and autophagy-related proteins. We further investigated the relationship between the inflammatory response and autophagy induced by MeHg by inhibiting them separately. The results indicated that MeHg could invade cells, change cell structure, activate NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and autophagosome, release a large amount of inflammatory factors and trigger the inflammatory response and autophagy. It was also found that MeHg could disrupt the antioxidant function of cells. In addition, the inhibition of NLRP3 inflammasome alleviated both cellular inflammation and autophagy, while inhibition of autophagy increased cellular inflammation. Our current research suggests that MeHg might induce BV2 cytotoxicity through inflammatory response and autophagy, which may be mediated by the NLRP3 inflammasome activated by oxidative stress.

The role of DRP1 mediated mitophagy in HT22 cells apoptosis induced by silica nanoparticles.

Silica nanoparticles (SiNPs) are widely used in the biomedical field and can enter the central nervous system through the blood-brain barrier, causing damage to hippocampal neurons. However, the specific mechanism remains unclear. In this experiment, HT22 cells were selected as the experimental model in vitro, and the survival rate of cells under the action of SiNPs was detected by MTT method, reactive oxygen species (ROS), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and adenosine triphosphate (ATP) were tested by the kit, the ultrastructure of the cells was observed by transmission electron microscope, membrane potential (MMP), calcium ion (Ca2+) and apoptosis rate were measured by flow cytometry, and the expressions of mitochondrial functional protein, mitochondrial dynein, mitochondrial autophagy protein as well as apoptosis related protein were detected by Western blot. The results showed that cell survival rate, SOD, CAT, GSH-Px, ATP and MMP gradually decreased with the increase of SiNPs concentration, while intracellular ROS, Ca2+, LDH and apoptosis rate increased with the increase of SiNPs concentration. In total cellular proteins,the expressions of mitochondrial functional proteins VDAC and UCP2 gradually increased, the expression of mitochondrial dynamic related protein DRP1 increased while the expressions of OPA1 and Mfn2 decreased. The expressions of mitophagy related proteins PINK1, Parkin and LC3Ⅱ/LC3Ⅰ increased and P62 gradually decreased, as well as the expressions of apoptosis related proteins Apaf-1, Cleaved-Caspase-3, Caspase-3, Caspase-9, Bax and Cyt-C. In mitochondrial proteins, the expressions of mitochondrial dynamic related proteins DRP1 and p-DRP1 were increased, while the expressions of OPA1 and Mfn2 were decreased. Expressions of mitochondrial autophagy associated proteins PINK1, Parkin, LC3II/LC3I increased, P62 decreased gradually, as well as the expressions of apoptosis related proteins Cleaved-Caspase-3, Caspase-3, and Caspase-9 increased, and Cyt-C expressions decreased. To further demonstrate the role of ROS and DRP1 in HT22 cell apoptosis induced by SiNPs, we selected the ROS inhibitor N-Acetylcysteine (NAC) and Dynamin-related protein 1 (DRP1) inhibitor Mdivi-1. The experimental results indicated that the above effects were remarkably improved after the use of inhibitors, further confirming that SiNPs induce the production of ROS in cells, activate DRP1, cause excessive mitochondrial division, induce mitophagy, destroy mitochondrial function and eventually lead to apoptosis.

Comparison of the transportation network for public transit and private vehicles in Shanghai: An accessibility approach.

This study examines the differences in service level and coverage of public transit (PT) and private vehicles (PV) with multi-source data in Shanghai. To construct computable networks and address visual results, the constrained shortest path algorithm and a spatial grid accessibility model are employed to seek the optimal path for travelers to city key points. Travel time ratio of PV and PT is applied to reflect the competitiveness of the two modes over different areas of Shanghai. Results show that for PV, although the average travel time meets the needs of car travel, 51 % of the population cannot get to graded city centers within 45 min. In addition, the PV accessibility gradually weakens from the central city to the outside, highways and expressways may be feasible solutions. For PT, half of the population can't reach any city key points within two transfers, and almost all of these people live in the suburbs. Less than 30 % of the population can reach the city key points within 1 h, of which rail transit contributes more than conventional buses. Furthermore, the travel accessibility of PV is much better than that of PT. The average travel time ratio in all comparable grids is 2.04 for hubs, and 2.10 for graded city centers. For travels to graded city centers, the travel time ratio of suburbs is 35 % higher than that of central city, indicating that the inequity distribution of public transportation resources is worse in the suburbs than in the central city. This study also measures equity performance of groups based on spatial location and income level, and we find out that more core locations and higher income lead to higher accessibility. The gap among groups is significant, with a Gini coefficient over 0.5.

From mundane to classic: Sinomenine as a multi-therapeutic agent.

Sinomenine is an active substance extracted from the traditional Chinese medicine Sinomenium acutum. Sinomenine has been shown to mediate a wide range of pharmacological actions and is known to possess good anti-inflammatory, immunosuppressive, antitumor, neuroprotective, antiarrhythmic and other pharmacological effects. Understanding the underlying mechanisms and the association between the targets and the pharmaceutical effects on different diseases is crucial to the discovery and design of new treatment strategies. In this review, we aim to give a systematic and comprehensive overview of the research progress of sinomenine over the past 20 years. We first describe the metabolism of sinomenine in vivo and then summarize the pharmacological actions of sinomenine on different diseases. Furthermore, the potential binding properties of sinomenine and the potential of developing new sinomenine-based drugs are also reviewed.

The anti-aging mechanism of ginsenosides with medicine and food homology.

With the acceleration of global aging and the rise in living standards, the achievement of healthy aging is becoming an imperative issue globally. Ginseng, a medicinal plant that has a long history of dietary intake and remarkable medicinal value, has become a research hotspot in the field of food and medicine. Ginsenosides, especially protopanaxadiol-type saponins and protopanaxatriol-type saponins, are among the most important active ingredients in ginseng. Ginsenosides have been found to exhibit powerful and diverse pharmacological activities, such as antiaging, antitumor, antifatigue and immunity enhancement activities. Their effects in antiaging mainly include (1) promotion of metabolism and stem cell proliferation, (2) protection of skin and nerves, (3) modulation of intestinal flora, (4) maintenance of mitochondrial function, and (5) enhancement of telomerase activity. The underlying mechanisms are primarily associated with the intervention of the signaling pathways in apoptosis, inflammation and oxidative stress. In this review, the mechanism of action of ginsenosides in antiaging as well as the potential values of developing ginsenoside-based functional foods and antiaging drugs are discussed.

Orbital adenoid cystic carcinoma treated by radiotherapy combined with anlotinib in a 13-year-old girl: A case report.

RATIONALE: Adenoid cystic carcinoma (ACC) of orbit is a very rare epithelial tumor, often originating from the lacrimal glands. At the same time, treatment options are currently limited, such as radiation, chemotherapy. We report a case of a patient treated with antirotinib combined with radiotherapy. PATIENT CONCERNS: A 13-year-old girl was initially admitted with "left eye swelling for over half a year, 12 days after surgery for left orbital adenoid cystic carcinoma". Initial swelling of the lateral upper eyelid of the left eye, with gradual enlargement and occasional pain. DIAGNOSES: Left orbital adenoid cystic carcinoma. INTERVENTIONS: After diagnosis of orbital ACC, she underwent resection of the left orbital mass, and received 33 times of adjuvant radiotherapy, but brain metastases appeared later. She refused further treatment, and received 25 times of radiotherapy and anlotinib therapy after the disease progressed again. OUTCOMES: Now the patient has been followed up for 8 months, but no progress was found. LESSONS: Based on this, we hypothesized that radiation therapy in combination with anlotinib is effective for ACC or ACC metastases.

Prospect of targeting lysine methyltransferase NSD3 for tumor therapy.

Nuclear receptor binding SET domain protein 3 (NSD3) has recently been recognized as a new epigenetic target in the fight against cancer. NSD3, which is amplified, overexpressed or mutated in a variety of tumors, promotes tumor development by regulating the cell cycle, apoptosis, DNA repair and EMT. Therefore, the inhibition, silencing or knockdown of NSD3 are highly promising antitumor strategies. This paper summarizes the structure and biological functions of NSD3 with an emphasis on its carcinogenic or cancer-promoting activity. The development of NSD3-specific inhibitors or degraders is also discussed and reviewed in this paper.

VDAC1 Protein Regulation of Oxidative Damage and Mitochondrial Dysfunction-Mediated Cytotoxicity by Silica Nanoparticles in SH-SY5Y Cells.

Silica nanoparticles (SiNPs) have been widely used in industry, electronics, and pharmaceutical industries. In addition, it is also widely used in medicine, tumor treatment and diagnosis, as well as other biomedical and biotechnology fields. The opportunities for people to contact SiNPs through iatrogenic, occupational, and environmental exposures are gradually increasing. The damage and biological effects of SiNPs on the nervous system have attracted widespread attention in the field of toxicology. Central nerve cells are rich in mitochondria. It is suggested that the effects of SiNPs on mitochondrial damage of nerve cells may involve the maintenance of neuronal membrane potential, the synthesis and operation of neurotransmitters, and the transmission of nerve pulses, and so on. We established an experimental model of SH-SY5Y cells to detect the cell survival rate, apoptosis, changes of reactive oxygen species and mitochondrial membrane potential, and the expression of mitochondrial function-related enzymes and proteins, so as to reveal the possible mechanism of SiNPs on neuronal mitochondrial damage. It was found that SiNPs could cause oxidative damage to cells and mitochondria, destroy some normal functions of mitochondria, and induce apoptosis in SH-SY5Y cells. The voltage-dependent anion channel 1(VDAC1) protein inhibitor DIDS could effectively reduce intracellular oxidative stress, such as the reduction of ROS content, and could also usefully restore some functional proteins of mitochondria to normal levels. The inhibition of VDAC1 protein may play an important role in the oxidative damage and dysfunction of neuronal mitochondria induced by SiNPs.

Hyper-thermophilic anaerobic pretreatment enhances the removal of transferable oxazolidinone and phenicol cross-resistance gene optrA in enterococci.

The extensive use of florfenicol in poultry industry results in the emergence of optrA gene, which also confers resistance to clinically important antibiotic linezolid. This study investigated the occurrence, genetic environments, and removal of optrA in enterococci in mesophilic (37 °C) and thermophilic (55 °C) anaerobic digestion systems, and a hyper-thermophilic (70 °C) anaerobic pretreatment system for chicken waste. A total of 331 enterococci were isolated and analyzed for antibiotic resistance against linezolid and florfenicol. The optrA gene was frequently detected in enterococci from chicken waste (42.7%) and effluents from mesophilic (72%) and thermophilic (56.8%) reactors, but rarely detected in the hyper-thermophilic (5.8%) effluent. Whole-genome sequencing revealed that optrA-carrying Enterococcus faecalis sequence type (ST) 368 and ST631 were the dominant clones in chicken waste, and they remained dominant in mesophilic and thermophilic effluents, respectively. The plasmid-borne IS1216E-fexA-optrA-erm(A)-IS1216E was the core genetic element for optrA in ST368, whereas chromosomal Tn554-fexA-optrA was the key one in ST631. IS1216E might play a key role in horizontal transfer of optrA due to its presence in different clones. Hyper-thermophilic pretreatment removed enterococci with plasmid-borne IS1216E-fexA-optrA-erm(A)-IS1216E. A hyper-thermophilic pretreatment is recommended for chicken waste to mitigate dissemination of optrA from animal waste to the environment.

Discovery of new tetrahydroisoquinolines as potent and selective LSD1 inhibitors for the treatment of MLL-rearranged leukemia.

Histone lysine-specific demethylase 1 (LSD1) is a promising target for cancer therapy. Here, we performed the design, synthesis, and extensive structure-activity relationship (SAR) studies based on our previously discovered natural LSD1 inhibitor, higenamine. We found that the tetracyclic tetrahydroisoquinoline FY-21 is a potent and selective inhibitor of LSD1 (IC50 = 340 nM). FY-21 inhibited leukemia cell proliferation and colony formation and increased the level of p53 expression. Meanwhile, FY-21 reduced the mRNA levels of the transcription factors HOXA9 and MEIS1. Furthermore, FY-21 significantly induced leukemia cell differentiation. In vivo studies showed that FY-21 prolonged the survival rate of leukemia mice. Collectively, FY-21 is a potent, selective LSD1 inhibitor and can serve as a lead compound for the development of novel and highly effective LSD1 inhibitors for AML treatment.

Pseudoprogression during immunotherapy for gastric adenocarcinoma: A case report and literature review.

Immunotherapy is a novel treatment option for various types of cancers. However, the optimal timing for response evaluation has not been well defined. Here, we present a gastric cancer (GC) patient with microsatellite instability-high who experienced recurrence 5 years and 11 months after radical gastrectomy. Then, the patient was treated with radiotherapy, targeted drugs, and immunotherapy. Immunotherapy resulted in 5 months of continuous progression, accompanied by significantly increased tumor marker CA19-9. However, the patient exhibited a satisfactory response without altering the treatment. Based on this, we hypothesized that some persistent progression with elevated tumor markers, known as pseudoprogression (PsP), might be observed in patients with recurrent GC during immunotherapy. This process might be prolonged, but if the treatment is continued, it will eventually produce remarkable therapeutic effects. PsP might challenge the globally accepted immune response evaluation criteria for solid tumors.

FRCNN-AA-CIF: An automatic detection model of colon polyps based on attention awareness and context information fusion.

It is noted that the foreground and background of the polyp images detected under colonoscopy are not highly differentiated, and the feature map extracted by common deep learning object detection models keep getting smaller as the number of networks increases. Therefore, these models tend to ignore the details in pictures, resulting in a high polyp missed detection rate. To reduce the missed detection rate, this paper proposes an automatic detection model of colon polyps based on attention awareness and context information fusion (FRCNN-AA-CIF) based on a two-stage object detection model Faster Region-Convolutional Neural Network (FR-CNN). First, since the addition of attention awareness can make the feature extraction network pay more attention to polyp features, we propose an attention awareness module based on Squeeze-and-Excitation Network (SENet) and Efficient Channel Attention Module (ECA-Net) and add it after each block of the backbone network. Specifically, we first use the 1*1 convolution of ECA-Net to extract local cross-channel information and then use the two fully connected layers of SENet to reduce and increase the dimension, to filter out the channels that are more useful for feature learning. Further, because of the presence of air bubbles, impurities, inflammation, and accumulation of digestive matter around polyps, we used context information around polyps to enhance the focus on polyp features. In particular, after the network extracts the region of interest, we fuse the region of interest with its context information to improve the detection rate of polyps. The proposed model was tested on the colonoscopy dataset provided by Huashan Hospital. Numerical experiments show that FRCNN-AA-CIF has the highest detection accuracy (mAP of 0.817), the lowest missed detection rate of 4.22%, and the best classification effect (AUC of 95.98%). Its mAP increased by 3.3%, MDR decreased by 1.97%, and AUC increased by 1.8%. Compared with other object detection models, FRCNN-AA-CIF has significantly improved recognition accuracy and reduced missed detection rate.

PD-1/PD-L1 Inhibitor Plus Chemotherapy Versus PD-1/PD-L1 Inhibitor in Microsatellite Instability Gastrointestinal Cancers: A Multicenter Retrospective Study.

PURPOSE: To investigate the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy versus anti-PD-1/PD-L1 monotherapy in advanced microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers. METHODS: We retrospectively recruited patients with MSI/dMMR gastrointestinal cancer who received anti-PD-1/PD-L1 with or without chemotherapy and compared objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 inhibitor plus chemotherapy (chemo-anti-PD-1/PD-L1 group) and PD-1/PD-L1 inhibitor alone (anti-PD-1/PD-L1 group). Propensity score-based overlap weighting analysis was conducted to adjust the baseline covariable imbalance. Sensitivity analysis was performed to confirm the stability of the results by propensity score matching and multivariable Cox and logistic regression models. RESULTS: A total of 256 patients were eligible, with 68 and 188 receiving chemo-anti-PD-1/PD-L1 and anti-PD-1/PD-L1, respectively. The chemo-anti-PD-1/PD-L1 group showed significant improvements versus the anti-PD-1/PD-L1 group in ORR (61.8% v 38.8%; P = .001), DCR (92.6% v 74.5%; P = .002), PFS (median PFS [mPFS], not reached [NR] v 27.9 months; P = .004), and OS (median OS [mOS], NR v NR; P = .014). After overlap weighting, the improvements tended to be more significant with chemo-anti-PD-1/PD-L1 versus anti-PD-1/PD-L1 in ORR (62.5% v. 38.3%; P < .001), DCR (93.8% v 74.2%; P < .001), PFS (mPFS, NR v 26.0 months; P = .004), and OS (mOS, NR v NR; P = .010). These results were solidified through sensitivity analysis. CONCLUSION: Chemo-anti-PD-1/PD-L1 is superior to anti-PD-1/PD-L1 in MSI/dMMR gastrointestinal cancers with improved efficacy.

Preparation of the monoclonal antibody against Nile tilapia Igλ and study on the Igλ+ B cell subset in Nile tilapia.

Immunoglobulins (Igs) are important effector molecules that mediate humoral immunity. A typical Ig consists of two heavy and two light chains. In teleosts, three Ig heavy chain isotypes (Igµ, Igδ and Igτ) and three Ig light chain isotypes (Igκ, Igλ and Igσ) have been identified. Compared to the heavy chains, teleost Ig light chains have been poorly studied due to the lack of antibodies. In this study, a mouse anti-Nile tilapia Igλ monoclonal antibody (mAb) was prepared, which could specifically recognize Igλ in serum and Igλ+ B cells in tissues. Further, the composition of IgM+ and Igλ+ B cell subsets was analyzed using this antibody and a mouse anti-tilapia IgM heavy chain mAb. The ratio of IgM+Igλ+ B cells to total IgM+ B cells in head kidney and peripheral blood was about 30%, while that in spleen was about 50%; the ratio of IgM-Igλ+ B cells to total Igλ+ B cells in head kidney and peripheral blood was about 45%, while that in spleen was about 25%. The IgM-Igλ+ B cells was speculated to be IgT+ B cells. Finally, we detected an increase in the level of specific antibodies against the surface antigen-Sip of Streptococcus agalactiae in serum after S. agalactiae infection, indicating that mouse anti-tilapia Igλ mAb can be used to detect the antibody level after immunization of Nile tilapia, which lays a foundation for the evaluation of immunization effect of tilapia vaccine.

The role and mechanism of unfolded protein response signaling pathway in methylmercury-induced apoptosis of mouse spermatocytes germ cell-2 cells.

The study aimed to explore the role and mechanism of unfolded protein response (UPR) in methylmercury (MeHg)-induced Mouse Spermatocytes (GC-2spd[ts]) apoptosis. Methods such as MTT, flow cytometry, and Western Blot were used to evaluate the cell viability, membrane potential (MMP), reactive oxygen species (ROS), calcium ion (Ca2+ ), rate of cell apoptosis, and the expression of apoptosis-related and UPR-related protein. The results showed that with the increase of MeHg concentration, cell viability and MMP decreased, ROS, Ca2+ , rate of cell apoptosis, and the expression of apoptosis-related protein and UPR-related protein increased. To further explore the effect of ROS-induced oxidative damage on it, the ROS inhibitor N-acetyl-L-cysteine (NAC) was used. The effects of MeHg on germ cell (GC-2) cells were partially inhibited after NAC pretreatment. Our present study proved that MeHg might induce cell apoptosis by activating the UPR signaling pathway in GC-2 cells and affect normal reproductive function.

Current and potential trends in the bioactive properties and health benefits of Prunus mume Sieb. Et Zucc: a comprehensive review for value maximization.

Prunus mume Sieb. Et Zucc (P. mume) is an acidic fruit native to China (named Chinese Mei or greengage plum). It is currently cultivated in several Asian countries, including Japan ("Ume"), Korea (Maesil), and Vietnam (Mai or Mo). Due to its myriad nutritional and functional properties, it is accepted in different countries, and its characteristics account for its commercialization. In this review, we summarize the information on the bioactive compounds from the fruit of P. mume and their structure-activity relationships (SAR); the pulp has the highest enrichment of bioactive chemicals. The nutritional properties of P. mume and the numerous uses of its by-products make it a potential functional food. P. mume extracts exhibit antioxidant, anticancer, antimicrobial, and anti-hyperuricaemic properties, cardiovascular protective effects, and hormone regulatory properties in various in vitro and in vivo assays. SAR shows that the water solubility, molecular weight, and chemical conformation of P. mume extracts are closely related to their biological activity. However, further studies are needed to evaluate the fruit's potential nutritional and functional therapeutic mechanisms. The industrial process of large-scale production of P. mume and its extracts as functional foods or nutraceuticals needs to be further optimized.

Industrial application of antimicrobial peptides based on their biological activity and structure-activity relationship.

Last several years, a rapid increase in drug resistance to traditional antibiotics has driven the emergence and development of antimicrobial peptides (AMPs). AMPs have also gained considerable attention from scientists due to their high potency in combatting infectious pathogens. A subset of analogues and their derivatives with specific targets have been successfully designed based on natural peptide patterns. In this review, scientific knowledge on the mechanisms of action related to biological activity and structure-activity relationship (SAR) of AMPs are summarized, and the biological applications in several important fields are critically discussed. SAR shows that the positive charge, secondary structure, special amino acid residues, hydrophobicity, and helicity of AMPs are closely related to their biological activities. The combination of nanotechnology, bioinformatics, and genetic engineering can accelerate to achieve the application of AMPs as effective, safe, economical, and nonresistant antimicrobial agents in medicine, the food and feed industries, and agriculture in coming years. Given the intense interest in AMPs, further investigations are needed in the future to evaluate the specific structure and function that make their use favorable in several industries. This review may provide a comprehensive reference for future studies on chemical modifications, mechanistic exploration, and applications of AMPs.

Recent two-year advances in anti-dengue small-molecule inhibitors.

Dengue is an acute tropical infectious disease transmitted by mosquitoes, which has posed a major challenge to global public health. Unfortunately, there is a lack of clinically proven dengue-specific drugs for its prevention and treatment. As the pathogenesis of dengue has not been fully elucidated, the development of specific drugs is seriously hindered. This article briefly describes the pathogenesis of dengue fever, the molecular characteristics, and epidemiology of dengue virus, and focuses on the potential small-molecule inhibitors of dengue virus, including on-target and multi-targeted inhibitors, which have been reported in the past two years.

Postmastectomy Radiotherapy Improves Survival Benefits in De Novo Stage IV Breast Cancer: A Propensity-Score Matched Analysis.

Purpose The role of postmastectomy radiotherapy (PMRT) in patients with de novo stage IV breast cancer is unclear. This study aimed to evaluate the value of PMRT for metastatic breast cancer who underwent a modified radical mastectomy. Methods: Data on de novo stage IV breast cancer patients who received modified radical mastectomy between 2010 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) analysis based on age, T stage, N stage, breast subtype, and chemotherapy was conducted to balance baseline clinical characteristics. The prognostic roles of PMRT on cancer-specific survival (CSS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazard models. Results: A total of 1944 patients were enrolled before PSM. After PSM, 1458 patients were included. PMRT improved the prognosis of CSS and OS. Multivariate Cox analysis showed that PMRT was independently prognostic for CSS (HR 0.739, 95% CI. 0.619-0.884, P = 0.001) and OS (HR 0.744, 95%CI 0.628-0.8810, P = 0.001). Further subgroup analyses found that survival superiority was observed in T3-4 or N + subgroup (both P < 0.001 for CSS and OS), and Her2-/HR + breast subtype (HR 0.703, 95%CI 0.558-0.888 for CSS, and HR 0.712, 95%CI 0.573-0.885 for OS), especially in patients with bone metastasis but without brain metastasis. Conclusion: PMRT improved survival in de novo stage IV breast cancer patients in selected T3-4 or N + subgroup and Her2-/HR + breast subtype. However, these findings need to be validated by further studies before being incorporated into clinical practice.

[Detection of Porphyromonas gingivalis rag genotypes in patients of chronic periodontitis with chronic obstructive pulmonary disease].

PURPOSE: To investigate the distribution of Porphyromonas gingivalis(P.g) rag genotypes in patients of chronic periodontitis with chronic obstructive pulmonary disease (COPD). METHODS: Thirty patients with chronic periodontitis and 30 patients with chronic periodontitis complicated with COPD were included. Saliva samples were collected from all subjects． The detection rate and rag genotype of P.g in saliva were detected by 16S rDNA polymerase chain reaction (PCR). SPSS 22.0 software package was used for statistical analysis. RESULTS: The positive rate of P.g was 76.67% in chronic periodontitis patients with COPD, and 63.33% in chronic periodontitis group, there was no significant difference between the two groups (P＞0.05). The detection rates of rag-1 genotype in the two groups were 70% and 30.77%, respectively, there was significant difference between the two groups(P＜0.05). The detection rates of rag-2, rag-3 and rag-4 in the two groups were not significantly different. CONCLUSIONS: Various rag genotypes can be found in patients of chronic periodontitis with COPD. Rag-1 might have more close correlation with the development of COPD.