The resistance and dose limitation of tumors is a serious obstacle to cytotoxic drug therapy in the field of medical oncology. Nitric oxide (NO) is a powerful adjuvant for tumor hypersensitivity for traditional chemotherapy and radiation therapy. The concentration of NO plays an important role in affecting its anti-tumor effect. This review summarizes the mechanism of concentration-dependent effects of NO on tumor cells and the mechanism of chemotherapy sensitization. It provides evidence for rational use of NO to exert anti-tumor effects, and overcoming multidrug resistance and anti-tumor drug development.

Based on the structure of inhibitors XL765 and WR23, the quinoxaline scaffold was selected as an attractive structure for drug design. In this protocol, the 2-position of quinoxaline was modified with a substituted phenoxy fragment. Meanwhile, the linking chain at the 3-position was changed to a sulfonyl hydrazine or was removed. A series of substituent groups were added at the 6-position of the quinoxaline scaffold. Twenty-two quinoline derivatives were designed and synthesized, and their structures were confirmed by ¹H NMR, ¹³C NMR, and ESI-MS. All compounds were screened for anti-tumor activity in vitro in A549, MCF-7, HCT-116 and HepG2 cancer cells. The results showed that P6b was effective, P6e and P6f had better activity against HCT116 (IC₅₀ = 3.24, 4.78 and 4.50 μmol·L^-1), and P6d had strong inhibitory effect on MCF-7 (IC₅₀ = 0.228 7 μmol·L^-1).

OBJECTIVE: To investigate the effect of prostaglandin E recoptor 4 antagonist (EPA) on the self-renewal ability of human CD34 cells and its mechamism. METHODS: The peripheral blood hematopoietic stem cell of 20 healthy donors received the G-CSF-mobilization were collected, then the human CD34 cells were sorted out by MACS microbead kit. The human CD34 cells were treated with DMSO (control group), EPA (EPA group) and EPA+EPA antagonist (EPA+EPA group) for 72 hours. The differential genes and pathways related with CD34 cell stemness were detected by Thermogram and Pathway enrichment analysis. and then the expression levels of protein and gene (β-catenin, Nanog, Oct4, Sox2, Stat3, AKT, P38) were detected by qRT-PCR and Western blot respectively. RESULTS: EPA could elevate the mRNA and protein expression of β-catenin, Nanog, Oct4, Sox2, in comparison with control group, however, mRNA and protein expression of STAT3, AKT, P38 were not changed. When human CD34 cell were cultured with EPA+XAV939 it was found that the mRNA and protein expression of β-catenin was downregulated, moreover the mRNA and protein expression of Nanog, Oct4, Sox2 were reduced. CONCLUSION EPA can upregulate stemness factors-β-catenin, Nanog, Oct4 and Sox2 in human CD34 cell in vitro, but not STAT3, AKT and P38.

As an important branch of artificial intelligence,the emerging medical artificial intelligence(MAI)is facing many ethical issues.MAI may offer the optimal diagnosis and treatment for patients but may also bring adverse effects on society and human beings.This article discusses the ethical problems caused by MAI and elucidates its development in a direction that meets ethical principles and requirements.

Objective: To explore the menopausal symptoms and quality of life of hormone receptor positive (HR+ ) breast cancer patients at different endocrine therapy time. Methods: The HR+ breast cancer patients who were pathologically confirmed from 2011 to 2017 in the Sichuan Cancer Hospital were divided into three groups according to endocrine therapy time (<12 months, 12~36 months, >36 months) and analyzed by a cross-sectional study. The Menopausal symptoms and quality of life of these patients were measured using the modified Kupperman scale and the functional assessment of cancer therapy-breast cancer (FACT-B) scale. The differences of menopausal symptoms among different time groups and drug groups were analyzed by Chi-square test. The differences of quality of life and the effects of menopausal symptoms on quality of life were tested by covariance and multiple linear regression analyses. Results: The average score of menopausal symptom of 167 patients was 14.5±7.6 and the prevalence rate was 87.4% (146/167). Among all of the menopausal symptoms, the prevalence rate of insomnia was the highest (73.7%, 123/167). Besides insomnia and excitement, hot flashes was more prevalent in selective estrogen receptor modulator (SERM) users (64.8%, 79/122) , while osteoarthritis was more prevalent in aromatase inhibitor (AI) users (62.2%, 28/45). The total score of FACT-B of Patients was 104.5±15.5, and the compliance rate was up to 89.8% (150/167). However, the condition of each dimension was different, the compliance rates of social/ family and functional dimension were lowest, which were 73.0% (122/167) and 50.9% (85/167), respectively. The menopausal symptoms of patients at different time groups were 15.0±1.3, 14.0±6.9, 14.5±7.4, respectively, and the total score of FACT-B of patients at different time groups were 102.7±17.8, 105.0±12.9, 105.6±16.7, respectively, without significant differences (both P>0.05). Multiple linear regression analysis showed that menopausal symptoms impaired the quality of life of SERM users during the endocrine therapeutic period. The standardized regression coefficients of three time groups were -0.67, -0.30, -0.50, respectively, with the lowest effect on 12~36 months group. Conclusion HR+ breast cancer patients will have a poor function recovery and social/ family return, who need more attention. Menopausal symptoms are common problems during endocrine therapy, and active measures should be taken to improve patients′ quality of life.

Interleukin ( IL) -38 is the most recently discovered cytokine, which is the tenth member of IL-1 cytokine family. IL-38 shares a high homology with IL-1 receptor antagonist ( IL-1 Ra) and IL-36 Ra. IL-36 R is the specific receptor of IL-38 which is the partial receptor antagonist of IL-36. Now, research has shown that IL-38 not only had relationship with intracellular infection and inflammation, but also with many clinical diseases such as autoimmune diseases, osteoarthritis, tumor and cardiopulmonary diseases. However, the molecular immune regulation mechanism of IL-38 is complicated, involving specific receptor recruitment, apoptosis mediated phagocyte regulation, regulation of Th17 cell differentiation and many other processes. It also provides several new clues to the treatment of diseases. IL-38 is a new cytokine research hot spot with extensive application prospects and need deep exploration.

OBJECTIVE: Patients with chronic neuropathic pain (CNP) have a higher incidence to develop depression. However, its pathogenesis has not yet been fully elucidated. Here we aimed to investigate the role of inflammatory cytokines in CNP-related anhedonia, which is a core symptom of depression, and to explore the effects of ketamine and parecoxib on pain and anhedonia. METHODS: A rat model of spared nerve injury (SNI) was constructed to mimic CNP. Hierarchical cluster analysis of sucrose preference test (SPT) was applied to classify the SNI rats into anhedonia susceptible and unsusceptible. Inflammatory cytokines in medial prefrontal cortex (mPFC) of brain, serum and L2–5 spinal cord were measured. Moreover, effects of ketamine or parecoxib on mechanical withdrawal test (MWT) and SPT in anhedonia susceptible rats were detected. RESULTS: Tumor necrosis factor (TNF)-α was increased in mPFC, serum and and spinal cord of anhedonia susceptible rats. Furthermore, anhedonia susceptible and unsusceptible rats both increased the interleukin (IL)-1β level in mPFC, serum and spinal cord. IL-6 was altered in serum and spinal cord, but not in mPFC. IL-10 was significantly altered in mPFC and serum, but not in spinal cord. Additionally, ketamine treatment significantly attenuated the decreased results of MWT and SPT in anhedonia susceptible rats, and that parecoxib significantly improved the MWT score, but failed to alter the result of SPT. CONCLUSION: These findings suggest that abnormalities in inflammatory cytokines confer susceptible to anhedonia in a rat model of SNI. Ketamine, a fast-acting antidepressant, has pharmacological benefits to alleviate pain and anhedonia symptoms.
Anhedonia ; Animals ; Brain ; Cytokines ; Depression ; Humans ; Incidence ; Interleukin-10 ; Interleukin-6 ; Interleukins ; Ketamine ; Models, Animal ; Neuralgia ; Neurogenic Inflammation ; Prefrontal Cortex ; Rats ; Spinal Cord ; Sucrose ; Tumor Necrosis Factor-alpha

Objective To explore the risk factors affecting prognosis of critically ill patients following cardiac surgery, furthermore, to assess severity and keep alarm earlier. Methods A retrospective study was conducted. The clinical data of critically ill patients following cardiac surgery admitted to intensive care unit (ICU) of the Affiliated Hospital of Guizhou Medical University from January 1st 2014 to December 31st 2018 were enrolled. The clinical characteristics, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and the worst laboratory examination within 24 hours after ICU admission, and the duration of mechanical ventilation, length of ICU stay, using continuous renal replacement therapy (CRRT), accepting vasoactive agents such as norepinephrine, dopamine or dobutamine and blood products such as red blood cells, plasma or platelets were recorded. The patients were divided into survival group and dead group based on discharge prognosis, and the difference in clinical data between the two groups was compared. Binary multivariate Logistic regression analysis was used to screen the risk factors affecting the prognosis of critically ill patients following cardiac surgery, and the receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of these risk factors. Results In total, 97 patients after cardiac operation were admitted to ICU during the five years. Thirty-two patients were excluded owing to age less than 16 years old, no more than 24 hours of the length of ICU stay, without the outcomes of myocardium enzymes or myocardium markers within the first 24 hours or admitted only for pacemaker. Finally, 65 patients met the criteria, with 40 survived and 25 died. Compared with survival group, APACHEⅡ scores, the level of serum uric acid, serum creatinine (SCr), cardiac troponin T (cTnT), brain natriuretic peptide (BNP), procalcitonin (PCT) and the rate of patients accepting CRRT, vasoactive agents and blood products in dead group were significantly increased with significant differences; however, there was no statistically difference in gender, age, body weight index (BMI), distribution of types of cardiac surgery, ratio of patients suffered from hypertension and diabetes, mean arterial pressure (MAP), white blood cell (WBC), coagulation, length of ICU stay, or duration of mechanical ventilation between the two groups. Binary multivariate Logistic regression analysis showed that APACHEⅡ scores [odds ratio (OR) = 1.123, 95% confidence interval (95%CI) = 1.004-1.257, P = 0.043] and cTnT (OR = 1.496, 95%CI = 1.038-2.158, P = 0.031) were the independent risk factors for prognosis of critical ill patients following cardiac surgery. ROC curve analysis showed that APACHEⅡ score and cTnT had predictive value for prognosis of critical ill patients following cardiac surgery, the best was exerted when APACHEⅡ score combined with cTnT, the area under the ROC curve (AUC) was 0.839, the joint prediction probability was 0.42, the sensitivity was 80.0%, and the specificity was 64.0%. Conclusion APACHEⅡscore and cTnT may be one of independent risk factors for prognosis of critical ill patients following cardiac surgery, and there will be far more greater predictive value when APACHEⅡ score combined with cTnT.

OBJECTIVE: To investigate the efficacy of disease control, survival time and safely in treatment of newly diagnosed multiple mycloma patients with different dose of tenalidomide regimens. METHODS: The clinical data of 116 patients with multiple myeloma from June 2011 to June 2015 were collected and analyzed retrospectively. According to doses of used lenalidomide based on dexamethasone plus lenalidomide regimen 116 patients were divided into 2 groups: conventional dose group (58 cases) and low dose group (58 cases). The ORR, PFS rate and OS rate during followed-up for 3 years, KPS score, RNS score and immunophenotypic index before and after treatment and drug toxicity incidence were compared between 2 groups. RESULTS: The ORR for 2 treatment courses of low dose group was significantly lower than that in conventienal dose group (P＜0.05). The ORR for 4 and 6 treatment courses was not significantly different between 2 groups (P＞0.05). The PFS rate and OS rate during followed-up for 3 years was no significantly different between 2 groups (P＞0.05). The KPS score and RNS score after treatment of low dose group were significantly better than those in conventional dose group and before treatment (P＜0.05). The levels of immunophenotypic index after treatment of both groups were significantly better than those before treatment (P＜0.05). The incidence of III-IV grade hematological toxicity, pulmonary infection and herpes were not significantly different between 2 groups (P＞0.05). The incidence of peripheral neuropathy and gastrointestinal reactions in the low dose group were significantly lower than that in conventional dose group (P＜0.05). CONCLUSION Conventional and low doses of lenalidomide possess the same control effects and survival time for treatment of newly dingnosed patients with multiple myeloma; Despite, the initiation of effects from the low dose lenalidomide is relatively slower, it contributes to raise the overall quality of life and reduce the risk of drug toxicity.
Antineoplastic Combined Chemotherapy Protocols ; Blood Coagulation ; Child ; Dexamethasone ; Humans ; Multiple Myeloma ; Purpura, Schoenlein-Henoch ; Quality of Life ; Retrospective Studies ; Thalidomide ; Thrombelastography ; Treatment Outcome

Adolescent ; Busulfan ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; Cyclosporine ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Infant ; Leukemia ; drug therapy ; mortality ; therapy ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; therapy ; Male ; Mycophenolic Acid ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; therapy ; Retrospective Studies ; Treatment Outcome