Ubiquitin E3 ligase activity of Ralstonia solanacearum effector RipAW is not essential for induction of plant defense in Nicotiana benthamiana.

As one of the most destructive bacterial phytopathogens, Ralstonia solanacearum causes substantial annual yield losses of many important crops. Deciphering the functional mechanisms of type III effectors, the crucial factors mediating R. solanacearum-plant interactions, will provide a valuable basis for protecting crop plants from R. solanacearum. Recently, the NEL (novel E3 ligase) effector RipAW was found to induce cell death on Nicotiana benthamiana in a E3 ligase activity-dependent manner. Here, we further deciphered the role of the E3 ligase activity in RipAW-triggered plant immunity. We found that RipAWC177A, the E3 ligase mutant of RipAW, could not induce cell death but retained the ability of triggering plant immunity in N. benthamiana, indicating that the E3 ligase activity is not essential for RipAW-triggered immunity. By generating truncated mutants of RipAW, we further showed that the N-terminus, NEL domain and C-terminus are all required but not sufficient for RipAW-induced cell death. Furthermore, all truncated mutants of RipAW triggered ETI immune responses in N. benthamiana, confirming that the E3 ligase activity is not essential for RipAW-triggered plant immunity. Finally, we demonstrated that RipAW- and RipAWC177A-triggered immunity in N. benthamiana requires SGT1 (suppressor of G2 allele of skp1), but not EDS1 (enhanced disease susceptibility), NRG1 (N requirement gene 1), NRC (NLR required for cell death) proteins or SA (salicylic acid) pathway. Our findings provide a typical case in which the effector-induced cell death can be uncoupled with immune responses, shedding new light on effector-triggered plant immunity. Our data also provide clues for further in-depth study of mechanism underlying RipAW-induced plant immunity.

[Water Quality Change Trend and Risk Analysis of Wuhan Hanjiang River Water Source].

Hanjiang River is closely related to the middle route of the South-to-North Water Diversion Project, the Water Diversion Project from the Hanjiang River to the Wei River, and the Water Diversion Project in Northern Hubei. The Wuhan Hanjiang River water source is one of the important drinking water sources in China; its water quality safety is significant to living and production for millions of residents in Wuhan. Based on data from 2004 to 2021, the water quality variation trend and risk of Wuhan Hanjiang River water source were studied. The results showed that a certain gap existed between the concentrations of some pollutants such as total phosphorus, permanganate index, ammonia nitrogen, and correspondent water quality target, especially for the total phosphorus. The growth of algae in the water source was marginally limited by the concentrations of nitrogen, phosphorus, and silicon. When other factors remained unchanged, diatoms tended to grow rapidly when the water temperature was appropriate (6-12℃). The quality of water upstream had a great impact on the water quality of the Hanjiang water source. There may have been pollutants entering into the reach during the West Lake Water Plant and Zongguan Water Plant. There were differences in the temporal and spatial variation trend of concentrations between permanganate index, total nitrogen, total phosphorus, and ammonia nitrogen. Significant changes in the ratio of nitrogen and phosphorus in the water body will affect the population structure and quantity of planktonic algae and ultimately affect the safety of water quality. The water body in the water source area was generally in the state of medium nutrition to mild eutrophication, and middle eutrophication may have occurred in a few periods. In recent years, the nutritional level of the water source has been on the decline. It is necessary to make an in-depth investigation on the source, quantity, and change trend of pollutants in water sources in order to eliminate potential risks.

Effectiveness of Inactivated Vaccine against SARS-CoV-2 Delta Variant Infection in Xiamen, China-A Test-Negative Case-Control Study.

OBJECTIVE: Vaccine effectiveness can measure herd immunity, but the effectiveness of inactivated vaccines in Xiamen remains unclear. Our study was designed to understand the herd immunity of the COVID-19 inactivated vaccine against the SARA-CoV-2 Delta variant in the real world of Xiamen. METHODS: We carried out a test-negative case-control study to explore the vaccine's effectiveness. Participants aged over 12 years were recruited. A logistic regression was used to estimate the odds ratio (OR) of the vaccine among cases and controls. RESULTS: This outbreak began with factory transmission clusters, and spread to families and communities during the incubation period. Sixty percent of cases were confirmed in a quarantine site. A huge mass of confirmed cases (94.49%) was identified within three days, and nearly half of them had a low Ct value. Following an adjustment for age and sex, a single dose of inactivated SARS-CoV-2 vaccine yielded the vaccine effectiveness (VE) of the overall case, of 57.01% (95% CI: -91.44~86.39%), the fully VE was 65.72% (95% CI: -48.69~88.63%) against COVID-19, 59.45% against moderate COVID-19 and 38.48% against severe COVID-19, respectively. The VE of fully vaccinated individuals was significantly higher in females than in males (73.99% vs. 46.26%). The VE among participants aged 19~40 and 41~61 years was 78.75% and 66.33%, respectively, which exceeds the WHO's minimal threshold. Nevertheless, the VE in people under 18 and over 60 years was not observed because of the small sample size. CONCLUSIONS: The single-dose vaccine had limited effectiveness in preventing infection of the Delta variant. The two doses of inactivated vaccine could effectively prevent infection, and clinical mild, moderate, and severe illness caused by the SARS-CoV-2 Delta variant in people aged 18-60 years in the real world.

Molecular subtypes predict the preferential site of distant metastasis in advanced breast cancer: a nationwide retrospective study.

Objective: This study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC). Methods: 3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites. Results: A total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07). Conclusion: Molecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.

The Ralstonia solanacearum Type III Effector RipAW Targets the Immune Receptor Complex to Suppress PAMP-Triggered Immunity.

Bacterial wilt, caused by Ralstonia solanacearum, one of the most destructive phytopathogens, leads to significant annual crop yield losses. Type III effectors (T3Es) mainly contribute to the virulence of R. solanacearum, usually by targeting immune-related proteins. Here, we clarified the effect of a novel E3 ubiquitin ligase (NEL) T3E, RipAW, from R. solanacearum on pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and further explored its action mechanism. In the susceptible host Arabidopsis thaliana, we monitored the expression of PTI marker genes, flg22-induced ROS burst, and callose deposition in RipAW- and RipAWC177A-transgenic plants. Our results demonstrated that RipAW suppressed host PTI in an NEL-dependent manner. By Split-Luciferase Complementation, Bimolecular Fluorescent Complimentary, and Co-Immunoprecipitation assays, we further showed that RipAW associated with three crucial components of the immune receptor complex, namely FLS2, XLG2, and BIK1. Furthermore, RipAW elevated the ubiquitination levels of FLS2, XLG2, and BIK1, accelerating their degradation via the 26S proteasome pathway. Additionally, co-expression of FLS2, XLG2, or BIK1 with RipAW partially but significantly restored the RipAW-suppressed ROS burst, confirming the involvement of the immune receptor complex in RipAW-regulated PTI. Overall, our results indicate that RipAW impairs host PTI by disrupting the immune receptor complex. Our findings provide new insights into the virulence mechanism of R. solanacearum.

Three amino acid residues are required for the recognition of Ralstonia solanacearum RipTPS in Nicotiana tabacum.

Ralstonia solanacearum causes devastating diseases in a wide range of economically important crops. It secretes a large number of virulence factors, also known as effectors, to promote its infection, and some of them are recognized when the host plant contains corresponding resistance genes. In this study we showed that a type III effector RipTPS from the avirulent R. solanacearum strain GMI1000 (RipTPSG) specifically induced cell death in Nicotiana tabacum, but not in Nicotiana benthamiana, whereas the RipTPS homolog in the virulent strain CQPS-1 (RipTPSC) induced cell death in neither N. tabacum nor N. benthamiana. These results indicated that RipTPSG is recognized in N. tabacum. Expression of RipTPSG induced upregulation of hypersensitive response (HR) -related genes in N. tabacum. The virulence of CQPS-1 was reduced when RipTPSG was genetically introduced into CQPS-1, further confirming that RipTPSG functions as an avirulence determinant. Protein sequence alignment indicated that there are only three amino acid polymorphisms between RipTPSG and RipTPSC. Site-directed mutagenesis analyses confirmed that the three amino acid residues are jointly required for the recognition of RipTPSG in N. tabacum. Expression of either RipTPSG or RipTPSC suppressed flg22-triggered reactive oxygen species (ROS) burst in N. benthamiana, suggesting that RipTPS contributes to pathogen virulence. Mutating the conserved residues in RipTPS's trehalose-phosphate synthase (TPS) domain did not block its HR induction and defense suppression activity, indicating that the TPS activity is not required for RipTPS's avirulence and virulence function.

Model-Based Evaluation of Transmissibility and Intervention Measures for a COVID-19 Outbreak in Xiamen City, China.

Background: In September 2021, there was an outbreak of coronavirus disease 2019 (COVID-19) in Xiamen, China. Various non-pharmacological interventions (NPIs) and pharmacological interventions (PIs) have been implemented to prevent and control the spread of the disease. This study aimed to evaluate the effectiveness of various interventions and to identify priorities for the implementation of prevention and control measures. Methods: The data of patients with COVID-19 were collected from 8 to 30 September 2021. A Susceptible-Exposed-Infectious-Recovered (SEIR) dynamics model was developed to fit the data and simulate the effectiveness of interventions (medical treatment, isolation, social distancing, masking, and vaccination) under different scenarios. The effective reproductive number (Reff ) was used to assess the transmissibility and transmission risk. Results: A total of 236 cases of COVID-19 were reported in Xiamen. The epidemic curve was divided into three phases (Reff = 6.8, 1.5, and 0). Notably, the cumulative number of cases was reduced by 99.67% due to the preventive and control measures implemented by the local government. In the effective containment stage, the number of cases could be reduced to 115 by intensifying the implementation of interventions. The total number of cases (TN) could be reduced by 29.66-95.34% when patients voluntarily visit fever clinics. When only two or three of these measures are implemented, the simulated TN may be greater than the actual number. As four measures were taken simultaneously, the TN may be <100, which is 57.63% less than the actual number. The simultaneous implementation of five interventions could rapidly control the transmission and reduce the number of cases to fewer than 25. Conclusion: With the joint efforts of the government and the public, the outbreak was controlled quickly and effectively. Authorities could promptly cut the transmission chain and control the spread of the disease when patients with fever voluntarily went to the hospital. The ultimate effect of controlling the outbreak through only one intervention was not obvious. The combined community control and mask wearing, along with other interventions, could lead to rapid control of the outbreak and ultimately lower the total number of cases. More importantly, this would mitigate the impact of the outbreak on society and socioeconomics.

Natural history and cycle threshold values analysis of COVID-19 in Xiamen City, China.

Objective: This study elaborated the natural history parameters of Delta variant, explored the differences in detection cycle thresholds (Ct) among cases. Methods: Natural history parameters were calculated based on the different onset time and exposure time of the cases. Intergenerational relationships between generations of cases were calculated. Differences in Ct values of cases by gender, age, and mode of detection were analyzed statistically to assess the detoxification capacity of cases. Results: The median incubation period was 4 days; the detection time for cases decreased from 25 to 7 h as the outbreak continued. The average generation time (GT), time interval between transmission generations (TG) and serial interval (SI) were 3.6 ± 2.6 days, 1.67 ± 2.11 days and 1.7 ± 3.0 days. Among the Ct values, we found little differences in testing across companies, but there were some differences in the gender of detected genes. The Ct values continuous to decreased with age, but increased when the age was greater than 60. Conclusion: This epidemic was started from aggregation of factories. It is more reasonable to use SI to calculate the effective reproduction number and the time-varying reproduction number. And the analysis of Ct values can improve the positive detection rate and improve prevention and control measures.

Age at initial diagnosis and prognosis of breast cancer: a nationwide multicenter retrospective study in China.

Background: Several studies have indicated possible associations between age and the prognosis of breast cancer (BC), but limited data are available from hospital-based multicenter studies in China. This study aimed to explore the associations between age at initial diagnosis of BC and the risk of recurrence or metastasis among Chinese women with newly diagnosed advanced breast cancer (ABC) and provide treatment decision support for BC patients of different ages to medical workers. Methods: The medical records of patients newly diagnosed with ABC were obtained from 21 hospitals in seven geographic regions in China from 2012 to 2014. Patients' general information, clinicopathological features at first diagnosis, treatment information, and prognosis were retrospectively collected based on the self-designed case report form (CRF). Cox proportional hazards regression models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for the associations between age groups and the risk of recurrence and metastasis. Results: A total of 1,852 cases were included in the final analysis. Age at initial diagnosis was shown to be significantly related to hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, molecular subtypes, and the number of lymph node metastasis (all P<0.05). Patients aged <35 years were more likely to have bone metastasis (45.6%). Patients aged ≥65 years had a lower percentage of receiving surgery (87.1%), adjuvant chemotherapy (61.3%), adjuvant radiotherapy (35.5%), and adjuvant endocrine therapy (30.6%) than the other groups (all P<0.05). Compared with patients aged <35 years, the risk of recurrence or metastasis in those aged 55-64 years was significantly higher (HRage 55-64 =1.24, 95% CI: 1.04-1.47), and the risk of bone metastasis and lung metastasis in those aged 35-44 years was lower (HRbone metastasis =0.74, 95% CI: 0.59-0.93; HRlung metastasis =0.70, 95% CI: 0.53-0.93). After adjusting for stage, grade, and molecular subtype, surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, adjuvant radiotherapy, adjuvant endocrine therapy, and family history of BC, patients aged 35-44 years still had a significantly reduced risk of bone metastasis and lung metastasis by 31% and 52%, respectively (HRbone metastasis =0.69, 95% CI: 0.48-0.98; HRlung metastasis =0.48, 95% CI: 0.31-0.74). Conclusions: Age at initial diagnosis is related to the clinicopathological characteristics and treatment pattern. Although the risk of site-specific metastasis varies by age, age is not an independent factor influencing the risk of total recurrence and metastasis. In accordance with current clinical practice guidelines for BC, however, precise treatment shall be chosen personally for patients whose ages at initial diagnosis are different.

A BTB/POZ domain-containing protein negatively regulates plant immunity in Nicotiana benthamiana.

Plants have evolved immune systems to fight against pathogens. However, it is still largely unknown how the plant immunity is finely regulated. Here we identified a BTB/POZ domain-containing protein, namely NbBTB, which is predicted to be a member of the ubiquitin E3 ligase complex. The NbBTB expression is downregulated upon the oomycete pathogen Phytophthora parasitica infection. Overexpression of NbBTB in Nicotiana benthamiana promoted plant susceptibility to P. parasitica infection, and silencing NbBTB increased plant resistance to P. parasitica, indicating that NbBTB negatively modulates plant basal defense. Interestingly, overexpressing or silencing NbBTB did not affect plant resistance to two bacterial pathogens Ralstonia solanacearum and Pseudomonas syringae, suggesting that NbBTB is specifically involved in basal defense against oomycete pathogen. Expression of NbBTB suppressed hypersensitive response (HR) triggered by avirulence proteins from both R. sonanacearum and P. infestans, and silencing NbBTB showed the opposite effect, indicating that NbBTB negatively regulates effector-triggered immunity (ETI). Protein accumulation of avirulence effectors in NbBTB-silenced plants was significantly enhanced, suggesting that NbBTB is likely to negatively modulate ETI by affecting effector protein accumulation. Together, our results demonstrated that NbBTB is a negative regulator in both plant basal defense and ETI.

Comparisons of Treatment for HER2-Positive Breast Cancer between Chinese and International Practice: A Nationwide Multicenter Epidemiological Study from China.

OBJECTIVE: To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice. METHODS: This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies. HER2-positive breast cancer was selected among the group and adopted into this study. In comparison, we summarized the demographics and clinical characteristics of HER2-positive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: A total of 918 patients diagnosed as HER2-positive breast cancer patients were included. The median age at diagnosis was 46 years (ranging, 23 to 78) with a single-peak incidence. The proportions of stages II-IV at diagnosis and distance metastasis in viscera were more than half of the participants. In comparison, the prevalence of estrogen or progesterone receptor-positive expression and luminalB subtype was relatively lower than that of the United States. The receipt of chemotherapy was fairly higher, while the usage of targeted therapy was seriously insufficient. Tumor size was in significantly positive associations with the duration of targeted therapy (Kendall's correlation coefficient = 0.3, P < 0.0001), while no prohibitive variables among clinical characteristics were detected. CONCLUSION: Our study suggested that HER2-positive breast cancer patients were characterized as a younger trend, a lower prevalence of hormonal receptor (HR)-positive expression, and less accessible to anti-HER2 targeted therapy with insufficient duration over the past few years in China. Concerted efforts should be exerted for promising survival benefits in the future. The trial registration number is https://clinicaltrials.gov/ct2/show/NCT03047889.

Enforcing trustworthy cloud SLA with witnesses: A game theory-based model using smart contracts.

There lacks trust between the cloud customer and provider to enforce traditional cloud SLA (Service Level Agreement) where the blockchain technique seems a promising solution. However, current explorations still face challenges to prove that the off-chain SLO (Service Level Objective) violations really happen before recorded into the on-chain transactions. In this paper, a witness model is proposed implemented with smart contracts to solve this trust issue. The introduced role, "Witness", gains rewards as an incentive for performing the SLO violation report, and the payoff function is carefully designed in a way that the witness has to tell the truth, for maximizing the rewards. This fact that the witness has to be honest is analyzed and proved using the Nash Equilibrium principle of game theory. For ensuring the chosen witnesses are random and independent, an unbiased selection algorithm is proposed to avoid possible collusions. An auditing mechanism is also introduced to detect potential malicious witnesses. Specifically, we define three types of malicious behaviors and propose quantitative indicators to audit and detect these behaviors. Moreover, experimental studies based on Ethereum blockchain demonstrate the proposed model is feasible, and indicate that the performance, ie, transaction fee, of each interface follows the design expectations.

MiR-34a suppresses osteoblast differentiation through glycolysis inhibition by targeting lactate dehydrogenase-A (LDHA).

Bone formation (osteogenesis) is mediated through recruitment of bone marrow mesenchymal stem cells (MSCs) with capacity to differentiate into osteoblasts, a process which is regulated by transcriptional and post-transcriptional mechanisms. Multiple studies have suggested that miRNAs might have important roles in osteoblast differentiation. Expressions of miR-34a were detected by qRT-PCR. Cellular glucose metabolism was assessed by measurements of glucose uptake and lactate production. mRNA expressions of glycolysis enzymes were detected by qRT-PCR. Osteogenic differentiation of human MSCs (hMSCs) was analyzed by alkaline phosphatase (ALP) activity and Alizarin red staining. Here, we report that microRNA-34a is upregulated during the osteoblast differentiation from hMSCs. miR-34a overexpressing inhibited late osteoblast differentiation of hMSCs in vitro. The ALP activity and Alizarin red staining were significantly decreased by miR-34a in hMSCs. Target prediction analysis reveals that the lactate dehydrogenase-A (LDHA) is a potential target of miR-34a. We hypothesized that miR-34a inhibits osteoblast differentiation through targeting the LDHA-mediated cellular glycolysis. Results from Western blotting and luciferase assay validated that miR-34a could directly target 3'UTR of LDHA mRNA. In addition, we demonstrated that overexpression of miR-34a inhibits cellular anaerobic glycolysis through targeting LHDA. The protein and mRNA expressions of glycolysis enzymes, Hexokinase 2 (HK2), glucose transporter 1 (GLUT1), and LDHA were significantly downregulated by miR-34a overexpression in hMSCs. Furthermore, we showed that LDHA restoration in miR-34a overexpressing hMSCs successfully rescued the osteoblast differentiation of hMSCs. This study demonstrated the roles of miR-34a in regulating osteoblast differentiation, suggesting that miR-34a inhibition could be a new therapeutic strategy for improving bone formation.

[Cancer pain, a serious threat to patientsmemory].

A large number of cancer patients suffer from pain. Growing evidence suggested that pain might be a serious risk factor for cancer patients. The shared modulators and modulation pathways between neural system and tumor cells, such as various neurotransmitters and neurogenic cytokines, provide essential basis for the effect of pain on tumor. In this article, we reviewed some possible mechanism of this process from two aspects: the systematic regulation of central nervous system on endocrine and immunity, and the regional regulation of peripheral nerves on tumor cells. The aim of this review is to provide more innovative knowledge about pain and cancer and to emphasize the importance of anti-pain in the therapy of cancer.

Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study.

BACKGROUND: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. METHODS: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. RESULTS: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. CONCLUSIONS: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.

Psychometric properties of the Chinese version of resilience scale specific to cancer: an item response theory analysis.

OBJECTIVE: Classic theory test has been used to develop and validate the 25-item Resilience Scale Specific to Cancer (RS-SC) in Chinese patients with cancer. This study was designed to provide additional information about the discriminative value of the individual items tested with an item response theory analysis. METHODS: A two-parameter graded response model was performed to examine whether any of the items of the RS-SC exhibited problems with the ordering and steps of thresholds, as well as the ability of items to discriminate patients with different resilience levels using item characteristic curves. RESULTS: A sample of 214 Chinese patients with cancer diagnosis was analyzed. The established three-dimension structure of the RS-SC was confirmed. Several items showed problematic thresholds or discrimination ability and require further revision. CONCLUSIONS: Some problematic items should be refined and a short-form of RS-SC maybe feasible in clinical settings in order to reduce burden on patients. However, the generalizability of these findings warrants further investigations.

Gefitinib induces lung cancer cell autophagy and apoptosis via blockade of the PI3K/AKT/mTOR pathway.

Gefitinib is a selective inhibitor of the tyrosine kinase epidermal growth factor receptor, which inhibits tumor pathogenesis, metastasis and angiogenesis, as well as promoting apoptosis. Therefore, gefitinib presents an effective drug for the targeted therapy of lung cancer. However, the underlying mechanisms by which gefitinib induces lung cancer cell death remain unclear. To investigate the effects of gefitinib on lung cancer cells and the mechanism of such, the present study analyzed the effect of gefitinib on the autophagy, apoptosis and proliferation of the A549 and A549-gefitinib-resistant (GR) cell lines GR. The regulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway was also investigated. Acridine orange staining revealed that gefitinib induced autophagy of A549 cells but not A549-GR cells. In addition, gefitinib promoted apoptosis and inhibited proliferation of A549 cells but not A549-GR cells. Furthermore, western blot analysis demonstrated that gefitinib treatment led to the downregulation of PI3K, AKT, pAKT, mTOR and phosphorylated-mTOR protein expression in A549 cells but not A549-GR cells. LY294002 blocked the PI3K/AKT/mTOR pathway and induced autophagy and apoptosis of A549 cells, however, no synergistic effect was observed following combined treatment with gefitinib and LY294002. In conclusion, the results of the present study indicate that gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway, which leads to lung cancer cell death.

Transdermal granisetron for the prevention of nausea and vomiting following moderately or highly emetogenic chemotherapy in Chinese patients: a randomized, double-blind, phase III study.

BACKGROUND: The granisetron transdermal delivery system (GTDS) has been demonstrated effectiveness in the control of chemotherapy-induced nausea and vomiting (CINV) in previous studies. This is the first phase III study to evaluate the efficacy and tolerability of GTDS in patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in China. METHODS: A total of 313 patients were randomized into the GTDS group (one transdermal granisetron patch, 7 days) or the oral granisetron group (granisetron oral 2 mg/day, ≥2 days). The primary endpoint was the percentage of patients achieving complete control (CC) from chemotherapy initiation until 24 h after final administration (PEEP). Chi-square test and Fisher's exact test were used for statistical analysis. RESULTS: Two hundred eighty-one patients were included in the per protocol analysis. During PEEP, CC was achieved by 67 (47.52%) patients in the GTDS group and 83 (59.29%) patients in the oral granisetron group. There was no statistical significance between the groups (P=0.0559). However, the difference of the CC percentage mainly occurred on the first day of chemotherapy between the groups. The CC was 70.13% on day 1 in the GTDS group, which was significantly lower than that of 91.03% in the oral granisetron group in the full analysis set. In the following days of chemotherapy, the CC was similar between the groups. In terms of cisplatin-contained regimen and female, there was statistical significance between the groups. Both treatments were well tolerated and safe. The most common adverse event was constipation. CONCLUSIONS: GTDS provided effective and well-tolerated control of CINV in Chinese patients, especially to non-cisplatin-contained regimen.

Laparoscopic temporary bilateral uterine artery occlusion with silicone tubing to prevent hemorrhage during vacuum aspiration of cesarean scar pregnancies.

AIM: The aim of this study was to determine the feasibility and effects of temporary bilateral uterine artery occlusion with silicone tubing on blood loss during vacuum aspiration of cesarean scar pregnancies (CSP). MATERIAL AND METHODS: Six patients with CSP underwent removal of gestational masses via vacuum aspiration. At the beginning of the procedure, all patients underwent laparoscopic temporary bilateral uterine artery occlusion with tubing. The main measurements were the operating time, operative blood loss, Doppler examination of the uterine arteries, and complications of procedure. RESULTS: The median operation time was 99 min, the median time needed to put the tubing in place (the time from the opening of the retroperitoneum to positioning of the tubing) was 45.5 min and the median time of bilateral uterine artery occlusion with tubing was 32.5 min. The median blood loss was 97.5 mL, and none of the patients required blood transfusion. Doppler examination showed no difference in the pre- and postoperative resistance or pulsatility indices of the uterine vessels. There were no conspicuous complications. The serum ß-human chorionic gonadotrophin level decreased to normal within 14-27 days after the operation. CONCLUSION: Laparoscopic temporary bilateral uterine artery occlusion with silicone tubing is an effective, minimally invasive procedure for reducing blood loss during vacuum aspiration in patients with CSP.

Influence of UGT1A1 gene methylation level in colorectal cancer cells on the sensitivity of the chemotherapy drug CPT-11.

OBJECTIVE: To study the influence of the methylation level of UGT1A1 gene related to CPT-11 metabolic enzymes in colorectal cancer cells on the sensitivity of chemotherapy drugs. METHODS: Test the changes in sensitivity of seven colorectal cancer cell strains that have been/not been subject to DAC treatment to CPT-11, analyze its correlation with CES2, UGT1A1 and GUSB mRNA expression according to IC50; screen the effective interference sequence of UGT1A1 siRNA, test the changes in cytotoxicity of CPT-11 after UGT1A1 siRNA is transfected, select RK0 cells and make them transfected with the chemosynthetic UGT1A1 siRNA after their UGT1A1 expression is restored with or without demethylation treatment. RESULTS: The sensitivity of different colorectal cancer cell strains to CPT-11 showed difference (P<0.05), UGT1A1 expression in colorectal cell lines had a negative correlation with the IC50 (r=0.790648, P<0.05), the interference efficiency of the screened UGT1A1 siRNA was up to 78%. The IC50 value of siRNA decreased by nearly one time after transfected with HT-29 (P<0.01); which of methylated RK0 cells of UGT1A1 gene increased instead after the demethylation treatment. However, the IC50 value of the demethylation treatment group increased compared with the non-demethylation treatment group after UGT1A1 siRNA was transfected. CONCLUSIONS: The cytotoxicity of CPT-11 to colorectal cancer cells has a negative correlation with UGT1A1 expression, and positive correlation with CES2 and GUSB. The specific silencing UGT1A1 gene of siRNA could significantly increase the sensitivity of CPT-11 to the chemotherapy of colorectal cancer cells. UGT1A1 methylation was an important factor affecting the chemosensitivity of CPT-11.