Inter-equipment validation of PET-based radiomics for predicting EGFR mutation statuses in patients with non-small cell lung cancer.

AIM: To validate the inter-equipment generality of the radiomics based on PET images to predict the EGFR mutation status of patients with non-small cell lung cancer. MATERIALS AND METHODS: Patients were retrospectively collected in the departments of nuclear medicine of Heyi branch (Siemens equipment) and East branch (General Electric (GE) equipment) of the first affiliated hospital of Zhengzhou university. 5 predicting logistic regression models were established. The 1st one was trained and tested by the GE dataset; The 2nd one was trained and tested by the Siemens dataset; The 3rd one was trained and tested by the mixed dataset consisting of GE and Siemens. The 4th one was trained by GE and tested by Siemens; The 5th one was trained by Siemens and tested by GE. RESULTS: For the 1st ∼ 5th models, the mean values of AUCs for training/testing datasets were 0.78/0.73, 0.74/0.72, 0.75/0.70, 0.74/0.65 and 0.68/0.63, respectively. CONCLUSION: The AUCs of the models trained and tested on the datasets from the same equipment were higher than those for different equipment. The inter-equipment generality of the radiomics was not good enough in clinical practice.

[Clinical distribution and drug resistance characteristics of carbapenem-resistant Klebsiella pneumoniae].

To explore the clinical distribution and drug resistance characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP), in order to provide reference for the prevention and treatment of CRKP infection. Retrospective analysis was performed on 510 clinical isolates of CRKP from January 2017 to December 2021, and strain identification and drug sensitivity tests were conducted by MALDI-TOF mass spectrometer and VITEK-2 Compact microbial drug sensitivity analyzer. The carbapenemase phenotype of CRKP strain was detected by carbapenemase inhibitor enhancement test. The CRKP strain was further categorized by immunochromogenic method and polymerase chain reaction (PCR) was used for gene detection. The results showed that 302 strains (59.2%) were derived from sputum, 127 strains (24.9%) from urine and 47 strains (9.2%) from blood. 231 (45.3%) were mainly distributed in intensive care, followed by 108 (21.2%) in respiratory medicine and 79 (15.5%) in neurosurgery. Drug susceptibility test result shows that the resistant rate of tigecycline increased from 1.0% in 2017 to 10.1% in 2021, the difference was statistically significant (χ2=14.444,P<0.05). The results of carbapenemase inhibitor enhancement test showed that 461 carbapenemase strains (90.4%) of 510 CRKP strains, including 450 serinase strains (88.2%), 9 metalloenzyme strains (1.8%), and 2 strains (0.4%) produced both serine and metalloenzyme. 49 strains (9.6%) did not produce enzymes. Further typing by immunochromogenic assay showed that 461 CRKP strains were KPC 450 (97.6%) and IMP 2 (0.4%). 7 NDM (1.5%); 2 strains of KPC+NDM (0.4%); PCR results were as follows: 450 strains of blaKPC (97.6%), 2 strains of blaIMP (0.4%), 7 strains of blaNDM (1.5%), and 2 strains of blaKPC+NDM (0.4%). In conclusion, CRKP strains mainly originated from sputum specimens and distributed in intensive care department, and the drug resistance characteristics were mainly KPC type in carbapenemase production. Clinical microbiology laboratory should strengthen the monitoring of CRKP strains, so as to provide reference for preventing CRKP infection and reducing the production of bacterial drug resistance.

[Emerging and comparative genomic analysis of a novel plasmid carrying blaKPC-2 in Citrobacter freundii].

Objective: To explore the drug resistance mechanism and gene structure characteristics of a carbapenemase-producing novel incompatibility group plasmid pNY2385-KPC from Citrobacter freundii. Methods: A multi-drug resistant strain was obtained from urine samples of patients with fever in the emergency ward of Li Huili Hospital, Ningbo Medical Center. Bacterial species was preliminary identified and finally confirmed by 16S rRNA gene amplification and the average nucleotide identity alignment, respectively. The minimum inhibitory concentrations of the antimicrobial agents were determined by VITEK 2 Compact System. The complete genome sequence was obtained by "third-generation" sequencing methods, and then detailed annotation of gene function and comparative genomic analysis of plasmid structure were carried out by BLASTP/BLASTN, RefSeq, ConservedDomains, ResFinder, Isfinder, etc. Results: The pNY2385-KPC carried by citrobacter freundii NY2385 belonged a novel incompatibility group, and contained blaKPC-2 and conjugative transfer (type Ⅳ secretory system, T4SS) genes, which could induce conjugative transfer. A total of 15 plasmids of the same type as pNY2385-KPC were retrieved by NCBI, which were from Citrobacter freundii, and the rest were from Serratia marcescens, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Raoultella planticola and other bacteria, and were broad-host-range plasmids. The sequence comparative analysis of all 6 of the novel plasmid from Citrobacter freundii showed that the structure of the novel plasmid had certain conserved property, with Tn6296 variant structure carrying blaKPC-2, and plasmid pCF1807-3 had both repApNY2385-KPC and repAIncX8. Conclusion: The pNY2385-KPC type plasmids in Citrobacter freundii carried blaKPC-2 resistance gene, which were divided into two subtypes: repApNY2385-KPC single replicator and repApNY2385-KPC/repAIncX8 complex replicator, belonging to broad-host-range plasmids. And as a mobile genetic element, the plasmids promote the spread of blaKPC-2.

[Analysis on the secondary attack rates of SARS-CoV-2 Omicron variant and the associated factors].

Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q1, Q3) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q1, Q3) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.

Bacillus amyloliquefaciens TL106 protects mice against enterohaemorrhagic Escherichia coli O157:H7-induced intestinal disease through improving immune response, intestinal barrier function and gut microbiota.

AIMS: This study evaluated the effects of Bacillus amyloliquefaciens TL106, isolated from Tibetan pigs' faeces, on the growth performance, immune response, intestinal barrier function, morphology of jejunum, caecum and colon, and gut microbiota in the mice with enterohaemorrhagic Escherichia coli (EHEC)-induced intestinal diseases. METHODS AND RESULTS: In all, 40 female C57BL/6J mice were randomly divided into four groups: mice fed a normal diet (Control), mice oral administration of TL106 daily (Ba), mice challenged with EHEC O157:H7 on day 15 (O157) and mice oral administration of TL106 daily and challenged with EHEC O157:H7 on day 15 (Ba+O157). The TL106 was administrated to mice for 14 days, and mice were infected with O157:H7 at day 15. We found that TL106 could prevent the weight loss caused by O157:H7 infection and alleviated the associated increase in pro-inflammatory factors (TNF-α, IL-1ß, IL-6 and IL-8) and decrease in anti-inflammatory factor (IL-10) in serum and intestinal tissues of mice caused by O157:H7 infection (P < 0·05). Additionally, TL106 could prevent disruption of gut morphology caused by O157:H7 infection, and alleviate the associated decrease in expression of tight junction proteins (ZO-1, occludin and claudin-1) in jejunum and colon (P < 0·05). In caecum and colon, the alpha diversity for bacterial community analysis of Chao and ACE index in Ba+O157 group were higher than O157 group. The TL106 stabilized gut microbiota disturbed by O157:H7, including increasing Lachnospiraceae, Prevotellaceae, Muribaculaceae and Akkermansiaceae, and reducing Lactobacillaceae. CONCLUSIONS: We indicated the B. amyloliquefaciens TL106 can effectively protect mice against EHEC O157:H7 infection by relieving inflammation, improving intestinal barrier function, mitigating permeability disruption and stabilizing the gut microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacillus amyloliquefaciens TL106 can prevent and treat intestinal disease induced by EHEC O157:H7 in mice, which may be a promising probiotic for disease prevention in animals.

[Risk factors of carbapenem resistant Acinetobacter baumannii infection in intensive care unit].

Objective: This study will analyze the clinical characteristics and risk factors that may be related to the 30-day mortality of patients infected with CRAB in intensive care unit (ICU), and explore the resistance of CRAB and its influence on mortality. Methods: From December 2012 to February 2021, 173 ICU patients with CRAB infection in the Fifth Medical Center of PLA General Hospital were selected as the research objects, and the relevant data were collected for retrospective analysis. There were 119 cases (68.8%) in survival group and 54 cases (31.2%) in the non-survival group. Patients with CRAB infection were (52.9±13.5) years old, including 140 males (80.9%) and 33 females (19.1%).The first detected CRAB was collected, and antibiotic sensitivity test was conducted after the strain was resuscitated to analyze the antibiotic resistance. Univariate and multivariate Cox models were used to analyze independent risk factors associated with 30-day mortality in patients with CRAB infection. Results: Univariate and multivariate Cox analysis showed that acute physiology and chronic health evaluation scoring system Ⅱ(APACHE Ⅱ)(HR=1.058, 95%CI:1.012-1.106, P=0.013) and septic shock (HR=6.240, 95%CI:2.227-17.483, P<0.001) were independent risk factors related to 30-day mortality in ICU patients with CRAB. Treatment with ß-lactamase inhibitor (HR=0.496, 95%CI: 0.275-0.893, P<0.019) can reduce the 30-day mortality of patients with CRAB infection in ICU. The resistance rate of CRAB to cephalosporins, carbapenems, aminoglycosides and quinolones were more than 80%. The survival rate of patients infected by aminoglycoside resistant CRAB is low(χ²=4.012,P<0.05). Conclusion: The APACHE Ⅱ score, septic shock and use of ß-lactamase inhibitors were independent factors associated with the 30-day mortality in ICU patients with CRAB infection.

[Construction of urban scale-free network model and its epidemiological significance in the prevention and control of COVID-19].

COVID-19 is a public health emergency currently. In this study, a scale-free network model is established based on the Spring Migration data in 2020.The cities is clustered into three different modules. The epidemic of the cities in the black module was the most serious, followed by the red and the cyan. The black module contains 9 cities in Zhejiang province and 8 cities in Guangdong province, most of them located in the southeast coastal economic belt. These cities should be the key cities for epidemic prevention and control.

WNT3A accelerates delayed alveolar bone repair in ovariectomized mice.

Our goal was to evaluate alveolar bone healing in OVX mice, and to assess the functional utility of a WNT-based treatment to accelerate healing in mice with an osteoporotic-like bony phenotype. INTRODUCTION: Is osteoporosis a risk factor for dental procedures? This relatively simple question is exceedingly difficult to answer in a clinical setting, for two reasons. First, as an age-related disease, osteoporosis is frequently accompanied by age-related co-morbidities that can contribute to slower tissue repair. Second, the intervals at which alveolar bone repair are assessed in a clinical study are often measured in months to years. This study aimed to evaluate alveolar bone repair in ovariectomized (OVX) mice and provide preclinical evidence to support a WNT-based treatment to accelerate alveolar bone formation. METHODS: OVX was performed in young mice to produce an osteoporotic-like bone phenotype. Thereafter, the rate of extraction socket healing and osteotomy repair was assessed. A liposomal WNT3A treatment was tested for its ability to promote alveolar bone formation in this OVX-induced model of bone loss. RESULTS: Bone loss was observed throughout the murine skeleton, including the maxilla, and mirrored the pattern of bone loss observed in aged mice. Injuries to the alveolar bone, including tooth extraction and osteotomy site preparation, both healed significantly slower than the same injuries produced in young controls. Given sufficient time, however, all injuries eventually healed. In OVX mice, osteotomies healed significantly faster if they were treated with L-WNT3A. CONCLUSIONS: Alveolar bone injuries heal slower in OVX mice that exhibit an osteoporotic-like phenotype. The rate of alveolar bone repair in OVX mice can be significantly promoted with local delivery of L-WNT3A.

[Cost-effectiveness analysis of rabies immunization strategy based on dynamic-decision tree model].

Objective: To evaluate the cost-utility of different immunization strategies for rabies in China, and to provide a reference for determining the optimal immunization strategy. Methods: The system dynamics model was used to simulate the epidemic of canine rabies and a decision tree model was conducted to analysis different immune strategies. Relevant probabilities were obtained through literature search and on-site investigation. Sensitivity analysis was used to explore the important influenced factors. Results: At baseline, from a social perspective, 70% vaccination of dogs was the optimal strategy compared to current vaccination strategy (43% vaccination in dogs, human category-Ⅱ exposure vaccination/category-Ⅲ exposure vaccination combined with RIG). The total cost was 14 084 354 CNY, and the total utility value was 22 078 616.23 QALYs, and the incremental cost-utility ratio was-62 148 147 CNY/QALY; if human vaccination was considered, 55% vaccination of dogs combined with strategy one was the optimal strategy, its incremental cost-utility ratio was-444 620 557 CNY/QALY. The probability that an injured dog carries rabies virus was the most sensitive parameter. When it was greater than 0.005 03, strategy four was the optimal strategy. When it was less than 82/100 000, strategy one was the optimal strategy; when it was between 82/100 000 and 120/100 000, strategy two was the optimal strategy; when it was between 120/100 000 and 503/100 000, strategy two was the optimal strategy. Conclusion: It was conducive to increase the vaccination coverage of canine for the prevention and control of rabies.

Post-exposure prophylaxis vaccination rate and risk factors of human rabies in mainland China: a meta-analysis.

Rabies is one of the major public health problems in China, and the mortality rate of rabies remains the highest among all notifiable infectious diseases. A meta-analysis was conducted to investigate the post-exposure prophylaxis (PEP) vaccination rate and risk factors for human rabies in mainland China. The PubMed, Web of Science, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical and Wanfang databases were searched for articles on rabies vaccination status (published between 2007 and 2017). In total, 10 174 human rabies cases from 136 studies were included in this meta-analysis. Approximately 97.2% (95% confidence interval (CI) 95.1-98.7%) of rabies cases occurred in rural areas and 72.6% (95% CI 70.0-75.1%) occurred in farmers. Overall, the vaccination rate in the reported human rabies cases was 15.4% (95% CI 13.7-17.4%). However, among vaccinated individuals, 85.5% (95% CI 79.8%-83.4%) did not complete the vaccination regimen. In a subgroup analysis, the PEP vaccination rate in the eastern region (18.8%, 95% CI 15.9-22.1%) was higher than that in the western region (13.3%, 95% CI 11.1-15.8%) and this rate decreased after 2007. Approximately 68.9% (95% CI 63.6-73.8%) of rabies cases experienced category-III exposures, but their PEP vaccination rate was 27.0% (95% CI 14.4-44.9%) and only 6.1% (95% CI 4.4-8.4%) received rabies immunoglobulin. Together, these results suggested that the PEP vaccination rate among human rabies cases was low in mainland China. Therefore, standardised treatment and vaccination programs of dog bites need to be further strengthened, particularly in rural areas.

[Clinical manifestations analysis of patients diagnosed with primary pulmonary mucosa-associated lymphoid tissue lymphoma].

Objective: To analyze the clinical features of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: A total of 14 cases diagnosed with primary pulmonary MALT lymphoma were collected from May 2007 to May 2017 in Zhongshan Hospital, Fudan University. The clinical features, pathological characteristics, diagnosis, treatment and prognosis were retrospectively analyzed. Results: All 14 cases were pathologically diagnosed with primary pulmonary MALT lymphoma. The biopsy tissues were obtained through the Video-assisted Thoracoscopic Surgery (VATS) (4 cases), percutaneous puncture (2 cases), and bronchoscopy (8 cases). Cell types of these tumors were centrocyte-like cells (10 cases), lymphocytoid cells (2 cases), and monocytoid B cells (2 cases). The B cell clonality was detected by IgH cloning test in 4 cases and 3 of them were demonstrated with monoclonal strips. MALT1 breakup gene was positive in 3 out of 6 examined cases using fluorescence in situ hybridization (FISH). As for the treatment, 8 patients underwent chemotherapy, 5 patients underwent surgical resection and 1 patient abandoned treatment. Twelve patients were followed up to 9 years. The tumor recurrence occurred in 2 patients and resulted their death. Conclusions: The clinical manifestations of primary pulmonary MALT lymphoma are lack of specificity. The pathology, immunohistochemistry, IgH cloning test and MALT1 breakup gene tested by FISH are the criteria for diagnosis.

Inference on Injury Mechanism of Ankle Fracture by Lauge-Hansen Classification.

OBJECTIVES: To explore the injury mechanism of ankle fracture inferred by the Lauge-Hansen classification with the application of medical imageology and its application value in forensic medicine. METHODS: A total of 32 ankle fracture cases with known injury mechanism were collected from January 2013 to May 2018, which were identified in Yongkang Public Security Bureau, Zhejiang Province. The Lauge-Hansen classification of ankle fracture was performed by three forensic experts based on the data of X-ray and CT image. Fisher's exact test and Kappa consistency analysis were performed by SPSS 20.0 statistical software to compare the results of the Lauge-Hansen classification with the injury mechanism of ankle fracture obtained through the criminal evidence. RESULTS: In 32 cases, 84.4% （27/32） ankle fractures were classified according to the Lauge-Hansen classification based on medical imaging. The mechanism of ankle fracture identified by the Lauge-Hansen classification was consistent with that obtained through the criminal evidence. CONCLUSIONS: Based on medical imaging, the Lauge-Hansen classification can be well applied to infer the injury mechanism of ankle fracture in part cases, and provide objective evidence for the crime scene reconstruction of criminal cases.

First report of the qnrA determinant in Shigella sonnei isolated from China.

We investigated the first presence of qnrA among Shigella sonnei clinical isolates in Jiangsu Province, China. The qnrA-positive isolates coexisted with the mutation in gyrA at codon 83, these isolates were resistant to nalidixic acid and 22·2% (2 of 9) of them were resistant to norfloxacin.

Mangiferin ameliorates Porphyromonas gingivalis-induced experimental periodontitis by inhibiting phosphorylation of nuclear factor-κB and Janus kinase 1-signal transducer and activator of transcription signaling pathways.

BACKGROUND AND OBJECTIVE: Mangiferin is a natural polyphenol compound with anti-inflammatory properties. However, there have been few reports on the effect of mangiferin on periodontitis. Here, we investigated the anti-inflammatory effects of this compound on experimental periodontitis and the underlying mechanisms. MATERIAL AND METHODS: Mice were inoculated with Porphyromonas gingivalis to induce periodontitis, and treated with mangiferin orally (50 mg/kg bodyweight, once a day) for 8 wk. Then, the alveolar bone loss was examined using a scanning electronic microscope. Expression of tumor necrosis factor-α (TNF-α) and the phosphorylation levels of nuclear factor-κB (NF-κB) and Janus kinase 1-signal transducer and activator of adhesion (JAK1-STAT) pathways in the gingival epithelium were detected using western blot analysis and immunohistochemical staining. RESULTS: The results showed that mice with periodontitis exhibited greater alveolar bone loss, stronger expression of TNF-α and higher phosphorylation levels of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia, compared with control mice with no periodontitis. Moreover, treatment with mangiferin could significantly inhibit alveolar bone loss, TNF-α production and phosphorylation of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia. CONCLUSION: Mangiferin has anti-inflammatory effects on periodontitis, which is associated with its ability to down-regulate the phosphorylation of NF-κB and JAK1-STAT1/3 pathways in gingival epithelia.

Phototransformation of 2,4,6-tribromophenol in aqueous solution: Kinetics and photolysis products.

In this research, we studied the phototransformation of 2,4,6-tribromophenol (TBP) by UV irradiation in aqueous solution. Effects of typical environmental factors (i.e., pH and the initial concentration of TBP, Fe3+ and NO2-) were also investigated. Results showed that the transformation process followed pseudo-first-order kinetics. The transformation rate constant of TBP decreased with increasing initial concentration and increased with increasing Fe3+ and NO2- concentrations as well as increasing pH. Ten photoproducts were tentatively identified after irradiation of TBP, according to HPLC-LTQ-Orbitrap MS and GC/MS analysis. Among them, two dihydroxylated dibromobenzene compounds (di-OH-DBB) were found to be predominant over the reaction time, indicating that hydrodebromination of TBP could be the main phototransformation mechanism. In addition, the identification of eight OH-PBDEs and di-OH-PBBs suggested that photodimerization might also be a reaction pathway for TBP photochemical reactions.

Source and risk factors of a cutaneous anthrax outbreak, Jiangsu, Eastern China, 2012.

Anthrax is still a severe public health problem and threat to human health. A cutaneous anthrax outbreak occurred in Jiangsu Province, a non-endemic anthrax region of eastern China, from July to August 2012. Epidemiological and laboratory investigation were initiated to trace the source of infection and identify the risk factors of the outbreak. On 25 July 2012, 17 persons were exposed to a sick cow, which had been imported from northeast China a few days previously. Of the 17 exposed, eight developed symptoms between 1 and 8 days and were diagnosed as cutaneous anthrax cases. Three main genes of Bacillus anthracis were detected from both human and cow meat samples, indicating that the outbreak was associated with this infected cow. A retrospective cohort study showed that contact with blood and presence of skin damage contributed to the case infection with B. anthracis. The outbreak highlights the need to enhance quarantine for imported livestock, which should have been vaccinated prior to importation, the significance of education for high-risk individuals, and training for primary healthcare workers even in anthrax-free areas.

Molecular detection and extraction of pyrene in plasma and tissues of Sprague-Dawley rats.

In this paper, an efficient method for determination of total pyrene concentration in the biological samples including plasma, liver, spleen, lung and kidney of Sprague-Dawley rats were investigated and established using steady-state fluorescence method. Equilibrium dialysis method was applied to determine plasma protein binding rate of pyrene. The results illustrated that the protein binding rate depends on the concentration of pyrene in plasma. Extraction of pyrene in plasma was studied by using biomedical nanopartical which was prepared from synthesized associating polymer poly(ethylene glycol) end-capped by hexadecane. The Critical Micelle Concentration (CMC) of the polymeric micelle in aqueous solution was determined to equal 0.0063 mg/mL using 1-pyrenemethanol as a fluorescent probe. The distribution of free pyrene and pyrene loaded nanoparticals in blood were determined. The results showed that over 95% of the free pyrene was distributed into the erythrocyte, and the pyrene-loaded nanoparticles were less distributed in to the erythrocyte than free pyrene, but it was higher than 60%. This study provides an efficient method to detect pyrene in different tissues as well as an extraction method at the molecular level, which might contribute to the development of modern molecular diagnosis and identification in vivo.

Reversal of cisplatin resistance by inhibiting PI3K/Akt signal pathway in human lung cancer cells.

Cisplatin is regularly used in the treatment of lung cancer. However, its efficacy is limited because of drug resistance. In this study, we found that Akt expression and activity was increased in lung cancer cells with acquired cisplatin resistance (A549/DDP cells and H460/DDP cells) when compared to their parental cells. Inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt kinase activity by its natural inhibitor, Wortmannin, could sensitize DDP-resistant cells to DDP and reverse DDP resistance. Combination treatment of Wortmannin with cisplatin is capable of increasing the mortality rate of both A549/DDP cells and H460/DDP cells. The present study also demonstrated that hyperactivation of PI3K/Aktpathway is closely associated with cisplatin resistance by regulating the Bax-mitochondria-mediated apoptosis pathway in human lung cancer. Inhibition of PI3K/Aktactivity in A549/DDP cells and H460/DDP cells could reverse cisplatin resistance by enhancing the effect of cisplatin on Bax oligomerization and release of Cytochrome C, allowing activation of the caspase-mediated apoptosis pathway. In conclusion, cisplatin resistance of lung cancer can be reversed via the inhibition of the PI3K/Akt signaling pathway. Therefore, both PI3K and Akt may be potential targets for overcoming cisplatin resistance in lung cancer.

Regulation of ATRIP protein abundance by RAD9 in the DNA damage repair pathway.

Genotoxic stress activates checkpoint signaling pathways that activate the checkpoint kinases ATM and ATR, halt cell cycle progression, and promote DNA repair. A number of proteins act in concert with ATR to phosphorylate Chk1, including RAD17, the RAD9-RAD1-HUS1 complex, ATR/ATRIP and TopBp1. However, how these proteins involved act in concert with one another to propagate and maintain the checkpoint response is not well understood. Here, we reported that upregulation of RAD9 protein increased the quantity of ATRIP, suggesting that RAD9 activation will induce more efficient accumulation of ATRIP in vivo. Furthermore, the DNA damage-induced ATRIP foci formation was faster in the mRad9-/- ES cells. Also, ATRIP interacts specifically with RAD9, but not HUS1 and RAD1. Taken together, we suggested that RAD9 could affect both the ATRIP protein levels and DNA damage-induced ATRIP foci formation. Thus, we propose a role of RAD9 in the ATR-Chk1 pathway that is necessary for successful formation of the damage-sensing complex and DNA damage checkpoint signaling.