Regular Use of Aspirin and Statins Reduces the Risk of Cancer in Individuals with Systemic Inflammatory Diseases.

Aspirin has shown potential for cancer prevention, but a recent large randomized controlled trial found no evidence for a reduction in cancer risk. Given the anti-inflammatory effects of aspirin, systemic inflammatory diseases (SID), such as osteoporosis, cardiovascular diseases, and metabolic diseases, could potentially modify the aspirin-cancer link. To investigate the impact of aspirin in people with SIDs, we conducted an observational study on a prospective cohort of 478,615 UK Biobank participants. Individuals with at least one of the 41 SIDs displayed a higher cancer risk than those without SIDs. Regular aspirin use showed protective effects exclusively in patients with SID, contrasting an elevated risk among their non-SID counterparts. Nonetheless, aspirin use demonstrated preventative potential only for 9 of 21 SID-associated cancer subtypes. Cholesterol emerged as another key mediator linking SIDs to cancer risk. Notably, regular statin use displayed protective properties in patients with SID but not in their non-SID counterparts. Concurrent use of aspirin and statins exhibited a stronger protective association in patients with SID, covering 14 common cancer subtypes. In summary, patients with SIDs may represent a population particularly responsive to regular aspirin and statin use. Promoting either combined or individual use of these medications within the context of SIDs could offer a promising chemoprevention strategy. SIGNIFICANCE: Individuals with systemic inflammatory diseases derive chemoprotective benefits from aspirin and statins, providing a precision cancer prevention approach to address the personal and public challenges posed by cancer.

Exploration of potential targets and mechanisms of naringenin in the treatment of nonalcoholic fatty liver disease through network pharmacology.

OBJECTIVE: This study aimed to use network pharmacology to investigate the molecular mechanisms and potential targets of naringenin (NR) for nonalcoholic fatty liver disease (NAFLD) treatment to offer new drug development ideas. METHODS: The structure and compound information of NR were obtained from PubChem and the traditional Chinese medicine system pharmacology database and analysis platform. The traditional Chinese medicine system pharmacology database and analysis platform Database, Comparative Toxicogenomics Database and Encyclopedia of Traditional Chinese Medicine Database were then used to predict the related targets of NR. Online mendelian inheritance in man, Disgenet, Gene cards, The therapeutic target database and Drug bank were used to screen NAFLD targets, and the intersection analysis was performed with the targets of NR active components to obtain the targets of NR in the treatment of NAFLD. The protein-protein interaction network of therapeutic targets was constructed by protein-protein interaction networks functional enrichment analysis 11.0, and gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis of therapeutic targets was performed by Metascape platform. RESULTS: In this study, 171 NR targets and 1748 potential targets of NAFLD were screened, and 89 crossover targets and 16 core targets were screened and finally obtained. A total of 176 GO items were obtained by GO enrichment analysis (P < .05), including 389 biological process, 6 cell composition and 30 molecular function. A total of 137 signaling pathways were obtained by Kyoto encyclopedia of genes and genomes pathway enrichment and screening (P < .05). The core targets of NR in the treatment of NAFLD are TP53, CASP3, PRKCA, AKT1, RELA, PPARG, NCOA2, CYP1A1, ESR1, MAPK3, STAT3, JAK1, MAPK1, TNF, PPARA and PRKCB. Enrichment analysis showed that NR mainly involved in biological processes such as cellular response to nitrogen compound, regulation of miRNA transcription and negative regulation of miRNA-mediated gene silencing. It regulates Hepatitis B, Lipid and atherosclerosis, cytomegalovirus infection, Hepatitis C, AGE-RAGE signaling pathway in diabetic patients complications and other ways play a role in the treatment of NAFLD. CONCLUSIONS: The therapeutic effect of NR on NAFLD has the characteristics of multi-targets and multi-pathways, which provides a preliminary theoretical basis for clinical trials and the development of new drugs.

PARP Inhibition Induces Synthetic Lethality and Adaptive Immunity in LKB1-Mutant Lung Cancer.

Contradictory characteristics of elevated mutational burden and a "cold" tumor microenvironment (TME) coexist in liver kinase B1 (LKB1)-mutant non-small cell lung cancers (NSCLC). The molecular basis underlying this paradox and strategies tailored to these historically difficult to treat cancers are lacking. Here, by mapping the single-cell transcriptomic landscape of genetically engineered mouse models with Kras versus Kras/Lkb1-driven lung tumors, we detected impaired tumor-intrinsic IFNγ signaling in Kras/Lkb1-driven tumors that explains the inert immune context. Mechanistic analysis showed that mutant LKB1 led to deficiency in the DNA damage repair process and abnormally activated PARP1. Hyperactivated PARP1 attenuated the IFNγ pathway by physically interacting with and enhancing the poly(ADP-ribosyl)ation of STAT1, compromising its phosphorylation and activation. Abrogation of the PARP1-driven program triggered synthetic lethality in NSCLC on the basis of the LKB1 mutation-mediated DNA repair defect, while also restoring phosphorylated STAT1 to favor an immunologically "hot" TME. Accordingly, PARP1 inhibition restored the disrupted IFNγ signaling and thus mounted an adaptive immune response to synergize with PD-1 blockade in multiple LKB1-deficient murine tumor models. Overall, this study reveals an unexplored interplay between the DNA repair process and adaptive immune response, providing a molecular basis for dual PARP1 and PD-1 inhibition in treating LKB1-mutant NSCLC. SIGNIFICANCE: Targeting PARP exerts dual effects to overcome LKB1 loss-driven immunotherapy resistance through triggering DNA damage and adaptive immunity, providing a rationale for dual PARP and PD-1 inhibition in treating LKB1-mutant lung cancers.

Complementary and alternative therapies for non-alcoholic fatty liver disease: A Bayesian network meta-analysis protocol.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a global pandemic, and its incidence is increasing year by year. At present, there are no definite curative drugs for the treatment of NAFLD in modern medicine. Surprisingly, complementary and alternative therapies play an important role and have special advantages. In this study, we will adopt Bayesian network meta-analysis (NMA) to evaluate the efficiency and safety of complementary therapy and alternative therapies for NAFLD. METHODS: We will collect randomized controlled trials (RCTs) related to the treatment of NAFLD in PubMed, Cochrane Library, CNKI, and other databases. Two reviewers will screen the literature and extract data in line with the inclusion and exclusion criteria, and then assess the risk of bias according to Cochrane risk of bias assessment tool. The Bayesian NMA will be performed by Stata16.0 and WinBUGS1.4.3. RESULTS: Our study will compare and rank the efficacy and safety of diverse complementary and alternative therapies for NAFLD. CONCLUSION: This study can provide credible evidence for the efficacy and safety of complementary therapies and alternative therapies in the treatment of NAFLD. We expect to assist clinicians and patients to choose the optimal therapeutic regimen. PROTOCOL REGISTRATION NUMBER: INPLASY2020120136.

Positive Distribution Rate of Coombs Test in Patients with Clinical Anemia and Blood Transfusion and Its Effect on Clinical Blood Transfusion / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the positive distribution rate of Coombs test in patients with clinical anemia and blood transfusion, and its effect on clinical blood transfusion.</p><p><b>METHODS</b>Seventy patients with hemoglobin level in the normal range were enrolled into control group, while 130 patients with anemia or blood transfusion who' s hemoglobin level was lower comfirmed by micro-column gel antihuman globin detection card and 70 surgical patients with anemia or blood transfusion who' s hemoglobin level was lower comfirmed by micro-column gel anti-human globin card were enrolled into anemia or blood transfusion (A or BT) group. And coomb' s test performed for all the patients, in which the positive patients in Department of Internal Medicine need to be re-typed.</p><p><b>RESULTS</b>Among 70 surgical patients with anemia or blood transfusion, 14 cases were directly detected to be anti-human globine positive with detection rate 20%; among 130 internal medicine patients with anemia or blood transfusion, 54 cases were directly detected to be anti-human globine positive with detection rate 41.4%. Among 270 cases, the highest positive rate (66.7%) was observed in patients with 50-59 g/L of hemoglobin. According to type test, the samples of 54 patients with anemia in Department of Internal Medicine, who were directly selected to be anti-human globin positive, could be divided into anti-C3d(7 cases, accounting for 13.0%), anti-IgG(12 cases accounting for, 22.2%) and anti-C3d+anti-IgG(35 cases, accounting for 64.8%), while according to diseases, the anti-human globin positive ratio was high in tumor cancer, hephropathy and gastroenteropathy patients, and patients in intensive care unit, moreover the blood transfusion frequency of these patients was higher than that of patients with anti-human globin negative(P<0.05).</p><p><b>CONCLUSION</b>The important causes affecting the anemia in patients may relate with direct anti- human globulin positive test, therefore the interference of direct anti-human globin positive should be excluded in the course of blood transfusion, so as to ensure the effectiveness of blood transfusion.</p>

Investigation and analysis of perceived occupational risk of nurses in nocturnal hemodialysis / 第二军医大学学报

Objective To investigate the occupational risk of nurses in nocturnal hemodialysis (NHD), and to analyze the relevant factors and coping approach to occupational risk. Methods The occupational risk of 25 nurses at conventional hemodialysis (CHD) and 25 nurses at NHD were investigated using Nursing Occupational Risk Assessment Questionnaire. The Likert Scale 5-grade method was used to score the questionnaire, to obtain occupational risk index, and to analyze the relevant risk factors. Results The scores in 3 dimensions, including accidental risk, chemical risk, and ergonomical, psychosocial and organizational risk, in the NHD nurse group were significantly higher than those in the CHD nurse group (P<0.05). The average risk index scores of the harzard of irregular working hours, interpersonal relation disturbance, frequent shift work, overtime, and night shift, and the hazard of understaffing and overworking were in the top 2 of each sub events, and they belonged to the risks which were order not allowed. Conclusion The average risk index of the nurses at NHD is higher than at CHD, and the formative factors are specific. Hospital managers should take active measures to prevent and reduce the occupational risk.

Long-pulse Nd:YAG 1064-nm laser treatment for onychomycosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent research shows that lasers can inhibit fungal growth and that Nd:YAG 1064-nm lasers can penetrate as deep as the lower nail plate. The aim of this study was to observe the effect of a long-pulse Nd:YAG 1064-nm laser on 154 nails of 33 patients with clinically and mycologically proven onychomycosis.</p><p><b>METHODS</b>Thirty-three patients with 154 nails affected by onychomycosis were randomly assigned to two groups, with the 154 nails divided into three sub-groups (II degree, III degree, and IV degree) according to the Scoring Clinical Index of Onychomycosis. The 15 patients (78 nails) in group 1 were given eight sessions with a one-week interval, and the 18 patients (76 nails) in group 2 were given four sessions with a one-week interval.</p><p><b>RESULTS</b>In group 1, the effective rates at 8 weeks, 16 weeks, and 24 weeks were 63%, 62%, and 51%, respectively, and the effective rates in group 2 were 68%, 67%, and 53% respectively. The treatment effect was not significantly different between any sub-group pair (P > 0.05).</p><p><b>CONCLUSIONS</b>Long pulse Nd:YAG 1064-nm laser was effective for onychomycosis. It is a simple and effective method without significant complications or side effects and is expected to become an alternative or replacement therapy for onychomycosis.</p>

A case of systemic amyloidosis beginning with purpura / 中华医学杂志(英文版)

Primary systemic amyloidosis is a relatively rare disease, caused when abnormal extracellular deposition of fibrillary protein builds up in a variety of target organs, such as heart, kidneys, lungs liver, and so forth. The symptoms of the disease are usually vague, while many kinds of auxiliary or laboratory examinations especially pathologic biopsy can provide a clue for the diagnosis. Here we described a case who had purpura-like lesions in the initial stage, followed by progressive malfunctions in the kidneys, the heart, the lungs, as well as the liver. The final diagnosis was primary systemic amyloidosis determined by skin pathologic biopsy. And the disease led to a fatal outcome within three months after the diagnosis.