Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non-Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked.

INTRODUCTION: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab. METHODS: This is a randomized, phase II, multicenter study evaluating carboplatin, pemetrexed, bevacizumab with and without atezolizumab in 117 patients with stage IV nonsquamous NSCLC. Randomization is 2 to 1 favoring the atezolizumab containing arm. Eligible patients include: 1) those with tumors with sensitizing EGFR alterations in exons 19 or 21 or 2) patients who have never smoked and have wild-type tumors (ie, no EGFR, ALK or ROS1 alterations). Patients are defined as having never smoked if they have smoked less than 100 cigarettes in a lifetime. Patients with EGFR-mutated tumors must have disease progression or intolerance to prior tyrosine kinase inhibitor (TKI) therapy. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), response rate, duration of response, and time to response. CONCLUSION: This phase II trial is accruing patients at U.S. sites through the National Comprehensive Cancer Network (NCCN). The trial opened in August 2019 and accrual is expected to be completed in the Fall of 2024.

Hyperprogressive disease in non-small cell lung cancer treated with immune checkpoint inhibitor therapy, fact or myth?

The therapeutic landscape for patients with non-small cell lung cancer (NSCLC) has dramatically evolved with the development and adoption of immune checkpoint inhibitors (ICI) as front-line therapy. These novel antibodies target the interactions in immunoregulatory pathways, between programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), or cytotoxic T-lymphocyte antigen 4 (CTLA-4) and B7, resulting in the activation of T cells and cytotoxic response to induce an immunologic response. ICIs have demonstrated significant survival benefits and sustained responses in the treatment of NSCLC leading to the long-term survival of up to 5 year. One unusual response to ICI is a phenomenon termed Hyperprogressive Disease (HYD), which occurs in a subset of patients for whom ICI therapy can induce rapid disease growth, which ultimately leads to poorer outcomes with an incidence rate ranging from 5 to 37% in NSCLC patients. Prior reviews demonstrated that HYD can be defined by rapid tumor progression, deterioration of patient's symptoms or new onset of disease. The mechanism of HYD could be related to genomic and tumor microenvironment changes and altered immune response. It will be important to establish a common definition of HYD for future research and clinical care.

Population-based study of environmental lead exposure and hearing loss: a systematic review and meta-analysis.

OBJECTIVES: Multiple studies suggest that there is an association between environmental lead exposure and hearing loss. However, the results of studies exploring the relationship between lead exposure and the occurrence of hearing loss are inconsistent. To clarify this issue, we conducted a meta-analysis to determine the association between lead exposure and hearing loss. STUDY DESIGN: This study was a meta-analysis. METHODS: A comprehensive literature search was performed using PubMed, Web of Knowledge, Elsevier ScienceDirect, and Springer databases. Eight articles involving 10 studies were included, and a random effect model was used for the meta-analysis. The Agency for Healthcare Research and Quality was used for judging the quality of the articles. RESULTS: Environmental lead exposure was significantly and substantially associated with hearing loss (combined odds ratio [OR] 1.42; 95% confidence interval [CI] 1.22-1.67) with mild heterogeneity (I2 = 47.0%, P = 0.049). Subgroup and sensitivity analyses confirmed the results; however, publication bias was evident. After the 'fill and trim' method, the recalculated OR was 1.36 (95% CI 1.12-1.64). CONCLUSIONS: The results of this study suggest an association between lead exposure and hearing loss. Exposure to a high concentration of lead was positively proportional to the risk of hearing loss. To eliminate the effects of other confounding factors, larger prospective cohort studies are required to further elucidate the relationship between lead exposure and hearing loss.

Treatment of Advanced-Stage Large Cell Neuroendocrine Cancer (LCNEC) of the Lung: A Tale of Two Diseases.

LCNEC of the lung comprises a small proportion of pulmonary malignancies. Traditionally, they have been classified based on histologic and immunohistochemistry characteristics with features of small cell and non-small cell lung cancer. The treatment outcome of advanced-stage LCNEC of the lung is poor with response rates ranging from 34 to 46% with platinum doublets, median progression-free survival (mPFS) ranging between 4.4 and 5.8 m, and median overall survival (mOS) ranging from 8 to 12.6 m. The optimal treatment strategy for LCNEC is debated given limited data and different outcomes based on chemotherapy type reported in the available literature. Recently, genomic profiling with Next Generation Sequencing (NGS) has been able to sub-classify LCNEC as SCLC-like or NSCLC-like. Treatment based on this sub-classification has improved outcomes by using SCLC and NSCLC regimens based on their genomic profile in retrospective analysis. Future studies in LCNEC of the lung should incorporate this new molecular sub-classification as stratification and possibly include SCLC-like LCNEC into SCLC studies and NSCLC-like into NSCLC studies.

Development of the Soft X-ray AGM-AGS RIXS beamline at the Taiwan Photon Source.

We report on the development of a high-resolution and highly efficient beamline for soft X-ray resonant inelastic X-ray scattering (RIXS) located at the Taiwan Photon Source. This beamline adopts an optical design that uses an active grating monochromator (AGM) and an active grating spectrometer (AGS) to implement the energy compensation principle of grating dispersion. Active gratings are utilized to diminish defocus, coma and higher-order aberrations, as well as to decrease the slope errors caused by thermal deformation and optical polishing. The AGS is mounted on a rotatable granite platform to enable momentum-resolved RIXS measurements with scattering angles over a wide range. Several high-precision instruments developed in-house for this beamline are described briefly. The best energy resolution obtained from this AGM-AGS beamline was 12.4 meV at 530 eV, achieving a resolving power of 4.2 × 104, while the bandwidth of the incident soft X-rays was kept at 0.5 eV. To demonstrate the scientific impact of high-resolution RIXS, we present an example of momentum-resolved RIXS measurements on a high-temperature superconducting cuprate, i.e. La2-xSrxCuO4. The measurements reveal the A1g buckling phonons in superconducting cuprates, opening a new opportunity to investigate the coupling between these phonons and charge-density waves.

Downregulation of miR-506-3p Facilitates EGFR-TKI Resistance through Induction of Sonic Hedgehog Signaling in Non-Small-Cell Lung Cancer Cell Lines.

Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR-targeted tyrosine kinase inhibitors (TKIs). Treatment resistance remains the primary obstacle to the successful treatment of NSCLC. Although drug resistance mechanisms have been studied extensively in NSCLC, the regulation of these mechanisms has not been completely understood. Recently, increasing numbers of microRNAs (miRNAs) are implicated in EGFR-TKI resistance, indicating that miRNAs may serve as novel targets and may hold promise as predictive biomarkers for anti-EGFR therapy. MicroRNA-506 (miR-506) has been identified as a tumor suppressor in many cancers, including lung cancer; however, the role of miR-506 in lung cancer chemoresistance has not yet been addressed. Here we report that miR-506-3p expression was markedly reduced in erlotinib-resistant (ER) cells. We identified Sonic Hedgehog (SHH) as a novel target of miR-506-3p, aberrantly activated in ER cells. The ectopic overexpression of miR-506-3p in ER cells downregulates SHH signaling, increases E-cadherin expression, and inhibits the expression of vimentin, thus counteracting the epithelial-mesenchymal transition (EMT)-mediated chemoresistance. Our results advanced our understanding of the molecular mechanisms underlying EGFR-TKI resistance and indicated that the miR-506/SHH axis might represent a novel therapeutic target for future EGFR mutated lung cancer treatment.

Hypereosinophilia (HE) in acute myeloid leukemia (AML) with normal karyotype: A report of two cases.

We present two rare cases of hypereosinophilia (HE) in acute myeloid leukemia with normal karyotype (NK-AML) at diagnosis. The first case is a 29-year-old female who presented with HE. On evaluation, she was found to have NK-AML. She failed to achieve complete remission (CR) after the first induction therapy with standard idarubicin and cytarabine (IA). She achieved CR after two cycles of reinduction chemotherapy with cytarabine, aclarubicin, and granulocyte colony-stimulating factor (G-CSF) (CAG) but had early relapsed. Reinduction chemotherapy with fludarabine, Ara-C, and G-CSF (FLAG) led to her second remission, followed by unrelated umbilical cord hematopoietic stem cell transplantation (HSCT). Unfortunately, she died of thrombotic thrombocytopenic purpura. The second case is a 23-year-old male who was diagnosed as NK-AML with HE. IA regimen was successively used in two cycles treatment achieving CR. He underwent haploidentical HSCT but had a relapse after 17 months of sustained remission and died 4 months later. The presence of HE may be a poor prognostic feature in NK-AML.

[Analysis of sleep quality of a prison police].

Objective: To investigate the sleep quality of prison policemen and explore its influencing factors, so as to provide reference for improving the sleep quality of prison policemen. Methods: In August 2013, 177 policemen in a prison were selected by cluster sampling. The sleep quality of 177 prison policemen was investigated by Pittsburgh Sleep Quality Index Scale and General Situation Questionnaire, and the influencing factors were analyzed. Results: The PSQI scores of 177 prison policemen were (7.47+3.80). There were significant differences between the PSQI scores of prison policemen and the normal adult norm (P<0.05). According to the standard of poor sleep quality, 84 prison policemen (47.46%) had poor sleep quality, and the prison policemen scored higher on daytime dysfunction, subjective sleep quality, sleeping time and sleeping time components. Single factor t test and single factor variance analysis showed that there were significant differences in sleep quality among prison policemen in gender, age, educational level and job classification (P <0.05). The results of multiple stepwise regression analysis showed that gender, age and job classification entered the regression equation with PSQI total score as dependent variable (ß=0.167, 0.270, 0.222) . Conclusion: The sleep quality of prison policemen is worse than that of normal adults, and is affected by gender, age, job classification and other factors, which should be paid attention to by prison administrators.

[Coexisting mutations in NPM1-mutated elderly adults with acute myeloid leukemia].

Objective: To explore the coexisting mutations in NPM1 mutated elderly patients with acute myeloid leukemia(AML). Methods: The clinical data of 152 elderly adults(aged≥60 years) and 49 young adults(aged 18-45 years) with AML between June 2013 and December 2018 in outpatient and hospitalized patients of Changzhou Second People's Hospital and Wuxi Second People's Hospital were retrospectively analyzed. A total of 51 gene mutations were detected using targeted next-generation sequencing (NGS) and sanger sequencing. The general clinical characteristics, the occurrence of coexistence gene mutations, the correlation between coexistence gene mutations and some clinical parameters, and the initial induction remission rate between elderly and young adult AML patients with NPM1 mutations were analyzed and compared. Results: NPM1 mutations were detected in 46 of 152 elderly AML patients. Thirty eight patients (82.6%) with NPM1 mutations carried other gene mutations at the same time, among whom 8 patients (17.4%) carried NPM1 mutations alone, while 14(30.4%) carried 2, 16 (34.8%) carried 3, and 8 (17.4%) carried ≥ 4 mutations. NPM1 mutations frequently co-occurred with FLT3-ITD15 cases (32.6%) , DNMT3A10 (21.7%) , TET26 (13.4%) and FLT3-TKD5 (10.9%) . Compared with young adults with NPM1 mutations, elderly patients had higher TP53, FLT3-TKD rates, lower incidence of DNMT3A, RAS mutation (all P<0.05) and lower coexistence rate of 4 gene mutations (P=0.002).The presence of ≥ 4 mutations was found to be significantly associated with higher white blood level than those in patients with single, double and 3 mutations coexisted in elderly adults AML patients(all P<0.05). With the increase of the amount of mutations, the complete remission(CR) rate decreased gradually after the initial induction. Patients who carried 3 or more mutations showed a lower CR rate than those with single gene mutations (all P<0.05) . Patients who carried>4 genes also showed a significantly lower CR rate than those with double gene mutations (P=0.031). Patients with FLT3-ITD mutations exhibited higher white blood level and lower CR rate than that in nonmutant type group (all P<0.05). The CR rate of patients with DNMT3A mutation was also significantly lower than that with nonmutant type (P=0.033). However, patients with FLT3-TKD mutations showed a higher platelet level than that with nonmutant type (P=0.019). There was no significant difference in CR rate and peripheral blood cell level between TET2 mutated and nonmutant type. Conclusion: NPM1 mutated elderly patients with AML commonly show additional mutations, and the amount and type of coexisting mutations have an influence on the clinical features and CR rate of elderly patients with AML.

Benign T cells drive clinical skin inflammation in cutaneous T cell lymphoma.

Psoralen plus UVA (PUVA) is an effective therapy for mycosis fungoides (MF), the skin-limited variant of cutaneous T cell lymphoma (CTCL). In low-burden patients, PUVA reduced or eradicated malignant T cells and induced clonal expansion of CD8+ T cells associated with malignant T cell depletion. High-burden patients appeared to clinically improve but large numbers of malignant T cells persisted in skin. Clinical improvement was linked to turnover of benign T cell clones but not to malignant T cell reduction. Benign T cells were associated with the Th2-recruiting chemokine CCL18 before therapy and with the Th1-recruiting chemokines CXCL9, CXCL10, and CXCL11 after therapy, suggesting a switch from Th2 to Th1. Inflammation was correlated with OX40L and CD40L gene expression; immunostaining localized these receptors to CCL18-expressing c-Kit+ dendritic cells that clustered together with CD40+OX40+ benign and CD40+CD40L+ malignant T cells, creating a proinflammatory synapse in skin. Our data suggest that visible inflammation in CTCL results from the recruitment and activation of benign T cells by c-Kit+OX40L+CD40L+ dendritic cells and that this activation may provide tumorigenic signals. Targeting c-Kit, OX40, and CD40 signaling may be novel therapeutic avenues for the treatment of MF.

Updates in the Clinical Development of Epacadostat and Other Indoleamine 2,3-Dioxygenase 1 Inhibitors (IDO1) for Human Cancers.

Recent application of immunotherapy in clinical oncology revolutionized our management of advanced human cancers. Check point inhibitors targeting CTLA4 and PD-1/PD-L1 axis are immunotherapeutic agents currently available to treat a variety of cancers. However, a novel therapeutic approach is needed to further improve patient outcome with these agents. Indoleamine 2,3-dioxygenase 1 (IDO1) is a rate-limiting enzyme in the metabolism of essential amino acid tryptophan in the peripheral tissue. IDO1 is overexpressed in human cancer cells and suppresses effector T cell function and promotes regulatory T cells (Tregs). Overexpression of IDO1 is associated with poor patient survival in several types of human cancer. These findings indicate that IDO1 is a promising target that can improve the treatment outcome in the field of Immuno-oncology. Several orally available IDO1 inhibitors including Epacadostat have entered human clinical trials over the last few years without a major safety concern. Although there is no objective response in single-agent trials, combination regimens with PD-1 inhibitors appear to exceed the activity of PD-1 inhibitors alone. Recent phase III ECHO 301 trial testing the combination of Epacadostat with Pembrolizumab in melanoma did not show superior outcome compared to Pembrolizumab alone. This lead to halting of other phase III trials using IDO1 inhibitors. In this minireview, we will discuss the recent clinical development of Epacadostat and other IDO1 inhibitors.

[Inhibitory Eefects of the novel tyrosine kinase inhibitor BGJ398 against human leukemic cell line KG-1 cells].

Objective: To explore the effects and possible mechanisms of the novel pan-FGFR inhibitor BGJ398 on KG-1 cells in vitro. Methods: Effects of BGJ398 on cells proliferation were detected by CCK-8, the apoptosis was assessed by Annexin V-FITC. Reverse transcriptionquantitative polymerase chain reaction (q-PCR) analysis was used to detect the expression of apoptosis-related genes B cell lymphoma-2 (Bcl-2) and caspase-3. Western blotting analysis was performed to explore the proteins expression levels of Bcl-2, caspase-3 and the expression of p-AKT, p-S6K, p-ERK and FGFR1. Results: BGJ398 effectively inhibited cell proliferation by dose-dependent manners. BGJ398(1.4 µmol/L) induced apoptosis of KG-1 cells by 36.4%, compared with 4.5% in the control group(P<0.001). Treatment with BGJ398 at 1.4 µmol/L led to significant increases in the expression levels of caspase-3, and decreases in the expression of Bcl-2 (P<0.005). In accordance with these results, Western blot analysis further confirmed the increased expression of Bcl-2 protein along with elevated caspase-3 activity. In addition, BGJ398 markedly down-regulated FGFR1OP2-FGFR1 fusion protein, p-AKT and p-S6K expression, but not p-ERK expression. Conclusion: Novel pan-FGFR inhibitor BGJ398 substantially suppressed KG-1 cell growth and induced apoptosis by inhibiting the expression of FGFR1, p-AKT, p-S6K and regulating apoptosis-related proteins.

Alpha-enolase regulates hepatitis B virus replication through suppression of the interferon signalling pathway.

Persistent chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of HBV-related diseases. The molecular mechanisms that underlie HBV infection and associated carcinogenesis are not fully understood. The aim of this study was to explore the role of ENO1 in HBV replication processes. Here, we examined ENO1 expression levels in HBV-infected and non-HBV-infected liver tissues and cells by Western blot analysis, real-time PCR and immunohistochemistry. In addition, HBsAg and HBeAg in the media of transfected HepG2.2.15 cells were detected using an electrochemical luminescence analyser within 48 hours after ENO1-specific siRNA transfection. The expression levels of HBV DNA, type I interferon and 5 downstream IFN-stimulated genes in HepG2.2.15 cells were examined using real-time PCR. We found ENO1 expression was upregulated in the HBV-infected liver tissues and cells. Silencing of ENO1 resulted in a significant reduction in HBV replication, and this siRNA-mediated reaction also caused the upregulation of expression of type I interferon and downstream IFN-stimulated genes. Therefore, we come to the conclusion ENO1 is involved in HBV replication. It is therefore likely that HBV replication is enhanced following suppression of the IFN signalling pathway. However, the mechanisms that underpin ENO1-mediated modulation of the IFN signalling pathway remain to be elucidated.

[A survey of sleep quality of employed nurses in military hospitals].

Objective: To investigate the sleep quality of the employed nurses in three grade A tertiary military hospitals in Beijing, China and its influential factors and to provide a reference for improving the sleep quality of employed nurses. Methods: From January 2014 to January 2017, a questionnaire survey was carried out to investigate the sleep quality of 253 employed nurses in three grade A tertiary military hospitals in Beijing, China using the Pittsburgh Sleep Quality Index (PSQI) and a general status questionnaire. The results were compared with the adult norms to analyze the influential factors for sleep quality of the employed nurses. Results: The global PSQI score of the 253 employed nurses was 7.76 ± 3.53. Their global PSQI score and PSQI component scores were significantly higher than the adults norms (P<0.05) . And 54.94% of the employed nurses had poor sleep quality; they had high scores of daytime dysfunction (1.39±0.83) , sleep latency (1.67±0.94) , sleep quality (1.33±0.88) , and sleep time (1.23±0.78) . The one-way analysis of variance showed that the sleep quality of the employed nurses was associated with nursing age, educational background, professional title, whether to have children, frequency of night shifts, and department (P<0.05) . The multivariate logistic regression analysis showed that the risk factors for sleep quality of the employed nurses were technical secondary school education (OR=4.292) and emergency department and intensive care unit (OR=2.582) ; the protective factors for sleep quality of the employed nurses were outpatient department and assistant department (OR=0.312) , no children (OR=0.318) , and no night shift (OR=0.332) . Conclusion: The employed nurses in military hospitals have poorer sleep quality than the normal adults. The influential factors for sleep quality of employed nurses are educational background, department, whether to have children, and frequency of night shifts.

[Clinical significance of JAK2、CALR and MPL gene mutations in 1 648 Philadelphia chromosome negative myeloproliferative neoplasms patients from a single center].

Objective: To explore the prevalences of JAK2, CALR and MPL gene mutations and the mutation types in patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) , and to compare their clinical characteristics of different mutation types with each other and mutation negative group. Methods: The mutations of JAK2 V617F, JAK2 gene at exon 12, CALR gene at exon 9 and MPL gene at exon 10 in 1 648 Ph negative MPNs patients were detected by direct sequencing. Results: ① The JAK2V617F mutation was found in 471 (92.7%) of 508 PV patients, 819 (78.1%) of 1 049 ET patients and 74 (81.3%) of 91 PMF patients respectively, with the total mutation rate as 82.8% (1 364/1 648) . The JAK2 exon12 mutation was found in 9 (1.7%) of 508 PV patients, none was found in ET or PMF patients, with the total mutation rate as 0.5% (9/1 648) . The CALR mutation was found in 132 (12.6%) of 1 049 ET patients and 11 (12.1%) of 91 PMF patients respectively, with the total mutation rate as 8.7% (143/1 648) ; the MPL mutation was found in 9 (0.9%) of 1 049 ET patients and 1 (1.1%) of 91 PMF patients respectively, with the total mutation rate as 0.6% (10/1 648) . The co-occurrence of any two types of driver gene mutations was not detected by direct sequencing. ②The median onset age of patients with JAK2V617F[61 (15-95) y] was significant higher than of with JAK2 exon12 mutation[49 (33-62) y] or without mutations[42 (3-78) y] (P<0.001) , but not for patients with CALR[57 (17-89) y] or MPL mutation[59 (22-71) y] (P>0.05) . Patients with JAK2V617F had higher white blood cell count and hemoglobin level (P<0.05) when compared with patients with CALR mutation or without mutations, or only significantly higher white blood cell count when compared with patients with MPL mutation (P=0.013) . The platelet count of patients with CALR mutation was significantly higher than of with JAK2V617F[966 (400-2 069) ×10(9)/L vs 800 (198-3 730) ×10(9)/L, P<0.001]. ③Karyotype analysis was conducted in 1 160 patients with MPNs, the rates of karyotype abnormality of patients with and without CALR mutation were 9.8% (8/82) and 7.4% (80/1 078) (P=0.441) respectively; The rates of karyotype abnormality of patients with and without JAK2V617F mutation were 7.7% (75/971) and 6.9% (13/189) (P=0.688) respectively. The incidence of karyotype abnormality of patients with CALR mutation was higher than of with JAK2V617F[9.8% (8/82) vs 7.7% (75/971) ] without statistically significant difference (P=0.512) . The karyotype analysis of 7 cases of JAK2 exon12 mutation and 6 ones with MPL gene mutation revealed normal karyotype. Conclusions: Driver gene mutations detection could ensure the diagnosis and prognosis judgment of MPN more reliable, different subtypes of MPNs had different profiles of driver gene mutations, the latter lead to unique clinical phenotype.

[Relationship between personality characteristics and turnover intention of medical staff in an infectious disease hospital].

Objective: To investigate the relationship between personality characteristics and turnover intention of the medical staff in an infectious diseases hospital. Methods: Using the cluster sampling method, a total of 366 members of medical staff were selected from different departments in an infectious disease hospital from May to August, 2013. The general information, such as sex, age, education level, and professional title, were collected and they were subjected to a survey using Cattell's 16 Personality Factor Questionnaire and Turnover Intention Scale. The data were subjected to logistic regression analysis. Results: Compared with the Chinese norm, the medical staff in the infectious disease hospital had significantly higher scores of intelligence, stability, bullying, excitability, perseverance, social boldness, fantasy, privateness, independence, and self-discipline and significantly lower scores of gregariousness, sensitivity, suspicion, anxiety, and tension (P<0.05). Of the 366 members of medical staff, 22 (6.01%) had a very low turnover intention, low in 152 (41.53%) , high in 61 (16.67%) , and very high in 131 (35.79%). The logistic regression analysis showed that sensitivity, suspicion, fantasy, privateness, anxiety, openness to change, and independence were the risk factors for turnover intention (P<0.05) . Conclusion: Compared with the Chinese norm, the medical staff in the infectious disease hospital have a better mental quality and a higher turnover intention. The individuals with sensitivity, suspicion, fantasy, and anxiety are prone to having turnover intention.

The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review.

Renal Cell Carcinoma (RCC) is the most prominent kidney cancer derived from renal tubules and accounts for roughly 85% of all malignant kidney cancer. Every year, over 60,000 new cases are registered, and about 14,000 people die from RCC. The incidence of this has been increasing significantly in the U.S. and other countries. An increased understanding of molecular biology and the genomics of RCC has uncovered several signaling pathways involved in the progression of this cancer. Significant advances in the treatment of RCC have been reported from agents approved by the Food and Drug Administration (FDA) that target these pathways. These agents have become drugs of choice because they demonstrate clinical benefit and increased survival in patients with metastatic disease. However, the patients eventually relapse and develop resistance to these drugs. To improve outcomes and seek approaches for producing long-term durable remission, the search for more effective therapies and preventative strategies are warranted. Treatment of RCC using natural products is one of these strategies to reduce the incidence. However, recent studies have focused on these chemoprevention agents as anti-cancer therapies given they can inhibit tumor cell grow and lack the severe side effects common to synthetic compounds. This review elaborates on the current understanding of natural products and their mechanisms of action as anti-cancer agents. The present review will provide information for possible use of these products alone or in combination with chemotherapy for the prevention and treatment of RCC.