Due to the advancement of 16S rRNA sequencing technology, the lower respiratory tract microbiota, which was considered non-existent, has been revealed. The correlation between these microorganisms and diseases such as tumor has been a hot topic in recent years. As the bacteria in the surrounding can infiltrate the tumors, researchers have also begun to pay attention to the biological behavior of tumor bacteria and their interaction with tumors. In this review, we present the characteristic of the lower respiratory tract bacteria and summarize recent research findings on the relationship between these microbiota and lung cancer. On top of that, we also summarize the basic feature of bacteria in tumors and focus on the characteristic of the bacteria in lung cancer. The relationship between bacteria in lung cancer and tumor development is also been discussed. Finally, we review the potential clinical applications of bacterial communities in the lower respiratory tract and lung cancer, and summarize key points of sample collection, sequencing, and contamination control, hoping to provide new ideas for the screening and treatment of tumors.
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Humans ; Lung Neoplasms ; RNA, Ribosomal, 16S/genetics* ; Bacteria/genetics* ; Microbiota ; Respiratory System ; Lung/microbiology*

The continuous advancement of molecular detection technology has greatly propelled the develop-ment of precision medicine for lung cancer.However,tumor heterogeneity is closely associated with tumor metastasis,recurrence,and drug resistance.Additionally,different lung cancer patients with the same genetic mutation may exhibit varying treatment responses to different therapeutic strategies.Therefore,the development of modern precision medicine urgently requires the precise formulation of personalized treatment strategies through personalized tumor models.Lung cancer organoid(LCO)can highly simulate the biological characteristics of tumor in vivo,facilitating the application of innovative drugs such as antibody-drug conjugate in precision medicine for lung cancer.With the development of co-culture model of LCO with tumor microenvironment and tissue engineering technology such as microfluidic chip,LCO can better preserve the biological characteristics and functions of tumor tissue,further improving high-throughput and automated drug sensitivity experiment.In this review,we combine the latest research progress to summarize the applica-tion progress and challenges of LCO in precision medicine for lung cancer.

Objective: On the basis of the dominant frequency index of functional connectivity, the "brain age" analysis method was used to explore abnormal development patterns of sensorimotor networks in boys with autism spectrum disorder(ASD). Methods: The resting state functional magnetic resonance data (7-12 years old) for 105 boys with ASD and 102 matched boys with normal development from the ABIDE public database were screened. Functional connection networks in different frequency bands of sensorimotor related brain regions were constructed for each individual, and the frequency of the strongest connection were constructed as the optimal frequency of the connection. Brain age analysis was used to explore the difference between brain age and chronological age in boys with ASD. Results: The brain sensorimotor network of boys with ASD showed an abnormal development pattern of overdevelopment followed by underdevelopment, and the transition between the two patterns occurred at approximately 7.8 years of age. Older boys with ASD (older than 10 years) whose underdevelopment trend was suppressed had lower ASD severity( r=-0.43, P < 0.05 ). Conclusion The brain sensorimotor network in boys with ASD has an abnormal development process, and the brain chronological age difference in the sensorimotor network has potential as a neuroimaging marker to measure the development of ASD.

Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Here, we found that oncoprotein hepatitis B X-interacting protein (HBXIP) blocked the myosin-IIA assemble state promoting breast cancer cell migration. Mechanistically, mass spectrometry analysis, co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain (ACD) of non-muscle heavy chain myosin-IIA (NMHC-IIA). The interaction was enhanced by NMHC-IIA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβII. Moreover, HBXIP induced the transcription of PRKCB, encoding PKCβII, by coactivating Sp1, and triggered PKCβII kinase activity. Interestingly, RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate (BZF) suppressed breast cancer metastasis via inhibiting PKCβII-mediated NMHC-IIA phosphorylation in vitro and in vivo. We reveal a novel mechanism by which HBXIP promotes myosin-IIA disassembly via interacting and phosphorylating NMHC-IIA, and BZF can serve as an effective anti-metastatic drug in breast cancer.

Lower extremity chronic total occlusion (CTO) is the most severe manifestation of peripheral artery disease (PAD), with high amputation and mortality rates. As a minimal invasive reconstruction therapy, endovascular therapy (EVT) plays an important role in limb salvage for CTO in current clinical practice. The complexity of CTO lesions leads to a high risk for complications and a low success rate of EVT. Therefore, establishing a grading or scoring system to predict the success rate of revascularization strategy will be helpful in developing appropriate treatment strategies and assessing benefits and risks. This paper summarizes the most popular CTO scoring systems, such as PACSS grading, PARC grading, TAC grading, CTOP classification, Infrapop-CTO scoring, and J-BTK CTO scoring. PACSS grading and PARC grading are suitable for evaluating the severity of vascular calcification including iliofemoral segment, femoral-popliteal segment, and below-the-knee artery segment. TAC grading is suitable for grading calcification below the knee lesions; with low intervention success rate in a high calcification grading. CTOP classification was developed by analyzing the effect of morphological characteristics of proximal and distal fibrous caps of lower extremity CTO lesions on the outcome of EVT. The success rate of antegrade intervention is lower in type IV. The Infrapop-CTO score and J-BTK CTO score can predict successful anterograde crossing of infrapopliteal CTO lesions, with low intervention success rate in high score. Both scoring systems use three variables, namely, shape of proximal stump, calcification, and occlusion length.

Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA (siRNA) for synergistic pancreatic cancer treatment. This "all-in-one" delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor (PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.

Lung cancer is one of the leading causes of cancer-related morbidity and mortality. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) have become the standard treatment for EGFR-mutated advanced non-small cell lung cancer (NSCLC). Unfortunately, drug resistance is inevitable in most cases. EGFR-TKI combined with angiogenesis inhibitors is a treatment scheme being explored to delay the therapeutic resistance, which is called "A+T treatment". Several clinical trials have demonstrated that the A+T treatment can improve the progression free survival (PFS) of the NSCLC patients. However, compared to EGFR-TKI monotherapy, the benefits of the A+T treatment based on different EGFR-TKIs, as well as its safety and exploration prospects are still unclear. Therefore, we reviewed the literature related to all three generations EGFR-TKIs combined with angiogenesis inhibitors, and summarized the mechanism, benefit, safety, optimal target population of A+T treatment.
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Angiogenesis Inhibitors/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use*

Objective To analyze serotype distribution, drug resistance, quinolone resistance gene carrying status and genetic relationship of foodborne Salmonella and human Salmonella isolates in Changzhou from 2012 to 2018, to provide scientific basis for the prevention and control of Salmonella. Methods The serum type was identified by serum agglutination and liquid chip. The antibiotic sensitivity was determined by micro broth dilution method. The quinolone antibiotic resistance gene was determined by gene sequencing method. The multilocus sequence typing ( MLST ) typing was performed on quinolone-resistant Salmonella, and the genetic relationship was analyzed by BioNumerics 8.0. Results A total of 10 and 36 serotypes were detected in 46 foodborne Salmonella strains and 152 human Salmonella strains, respectively. The dominant serotypes were Indiana Salmonella and Salmonella typhimurium. Erythromycin resistance rate was the highest in both Salmonella strains, and the proportion of multidrug-resistant bacteria was 93.47 % ( 43 / 46 ) and 80.92 % ( 123 / 152 ), respectively. 38 strains of quinolone-resistant foodborne Salmonella GyrA subunit mainly occurred double mutations Asp87Asn, Ser83Phe, ParC subunit mainly occurred single mutation Ser80Arg, 119 strains of quinolone-resistant human Salmonella qnrS gene detection rate was higher, reached 68.1 % ( 81 / 119 ) ; The dominant ST types of quinolone-resistant Salmonella from two sources were ST17 and ST19, respectively. Conclusions The antibiotic sensitivity of the two Salmonella resistant strains from Changzhou was the same ; Synergistic drug resistance, but both quinolone resistance genemutations and carry inconsistent ; The ST type distribution of quinolone resistant strains isalso inconsistent, and the genetic relationship is far. It is suggested that the probability of Salmonella resistant bacteria infection caused by food transmission in our region is small, and the treatment of the two should be differentiated.

Objective:To investigate the changes of advanced glycosylation end product(AGEs)/sodium-glucose cotransporter-1(SGLT-1) in intestinal and renal tissues and intestinal flora of mice with diabetes kidney disease.Methods:Twenty KKay mice were divided into diabetic group(DM group, n=10) and diabetic kidney disease group(DKD group, n=10). The concentrations of serum AGEs, lipopolysaccharide(LPS), tumor necrosis factor-α(TNF-α), and intereukin-6(IL-6) were measured. Western blot technique was used to detect the protein expression of AGEs and SGLT-1 in kidney and intestinal tissue, and high-throughput sequencing was used to analyze the difference of intestinal flora. Results:The levels of inflammatory markers TNF-α, IL-6, and serum endotoxin in DKD group were significantly higher than those in DM group( P<0.05). The contents of AGEs in serum and intestine and kidney were increased, and the contents of SGLT-1 in intestine and kidney were increased( P<0.05). Metastats test showed that the abundance of Verrucomicrobia decreased and the abundance of Proteobacteria increased in DKD group( P<0.05). G - bacteria such as Aeromonas, Enterobacter, Morgan, Klebsiella, Serratia, and Burkholderia were relatively dominant, and the abundance of Akkermansia was significantly lower than that in DM group( P<0.05). Conclusion:The increase of AGEs in intestinal tract of DKD mice may induce intestinal dysbacteriosis, especially the increase of Proteobacteria, the decrease of Verrucosa and Wilhelm Ackermann, and the leakage of G-bacteria into the blood to produce intestinal endotoxemia and cause inflammatory reaction, this may be an important factor in the development of DKD. SGLT-1 is elevated in intestinal tissue, which may be involved in the development of DKD.

Objective:To evaluate the safety and feasibility of the in-situ needle fenestration combined with the in vitro physician modified fenestration technique to reconstruct supra-aortic branches during thoracic endovascular aortic repair (TEVAR) for aortic arch lesions requiring landing at Z0 and Z1.Methods:From Nov 2017 to Dec 2019, eighteen patients who underwent both the in-situ needle fenestration and the in vitro physician modified fenestration techniques to extend the proximal landing zone to Z0 and Z1 during TEVAR were included in our study.Results:Sixteen patients underwent in vitro physician modified fenestration ,two patients underwent in vitro physician modified fenestration to reconstruct both the left common carotid artery and the innominate artery. All eighteen patients received in-situ needle fenestration to preserve the left subclavian artery. Supra aortic branches were preserved in all patients (38/38, 100%). There was no Type Ⅰ endoleak. Type Ⅱ endoleak was found in four paitnets (4/18). Type Ⅲ endoleak occurred in one patient (1/18). Type Ⅳ endoleak in four patients (4/18). Type Ⅲ endoleak needed open aortic arch repair 6 months later. The median follow-up time was 12 months. One (1/18) died in 12 months and the other patients were doing well.Conclusions:The joint application of the in-situ needle fenestration and the in vitro physician modified fenestration to reconstruct supra-aortic branches during TEVAR for aortic arch pathologies requiring landing at Z0 and Z1 was satisfactory.