PARP inhibition synergizes with CD47 blockade to promote phagocytosis by tumor-associated macrophages in homologous recombination-proficient tumors.

AIMS: PARP inhibitors (PARPi) are known to exert anti-tumor effects in patients with BRCA-mutated (BRCAmut) or homologous recombination (HR)-deficient cancer, but recent clinical investigations have suggested that this treatment may also be beneficial in patients with HR-proficient tumors. In this study, we aimed to investigate how PARPi exerts anti-tumor effects in non-BRCAmut tumors. MAIN METHODS: BRCA wild-type, HR-deficient-negative ID8 and E0771 murine tumor cells were treated in vitro and in vivo with olaparib, a clinically approved PARPi. The effects on tumor growth in vivo were determined in immune-proficient and -deficient mice and alterations of immune cell infiltrations were analyzed with flow cytometry. Tumor-associated macrophages (TAMs) were further investigated with RNA-seq and flow cytometry. In addition, we confirmed olaparib's effect on human TAMs. KEY FINDINGS: Olaparib did not affect HR-proficient tumor cell proliferation and survival in vitro. However, olaparib significantly decreased tumor growth in C57BL/6 and SCID-beige mice (defective in lymphoid development and NK cell activity). Olaparib increased macrophage numbers in the tumor microenvironment, and their depletion diminished the anti-tumor effects of olaparib in vivo. Further analysis revealed that olaparib improved TAM-associated phagocytosis of cancer cells. Notably, this enhancement was not solely reliant on the "Don't Eat Me" CD47/SIRPα signal. In addition, compared to monotherapy, the concomitant administration of αCD47 antibodies with olaparib improved tumor control. SIGNIFICANCE: Our work provides evidence for broadening the application of PARPi in HR-proficient cancer patients and paves the way for developing novel combined immunotherapy to upgrade the anti-tumor effects of macrophages.

The Effect of a Combined Ganciclovir, Methylprednisolone, and Immunoglobulin Regimen on Survival and Functional Outcomes in Patients With Japanese Encephalitis.

Objective: There is currently no effective treatment for Japanese encephalitis, which has a high rate of morbidity and mortality. This study assessed the effectiveness of a ganciclovir, methylprednisolone, and immunoglobulin combination (TAGMIC) therapy in decreasing cognitive impairment and mortality among patients with Japanese encephalitis. Methods: We retrospectively assessed the clinical data of 31 patients diagnosed with Japanese encephalitis, who were admitted to an intensive care unit. Patients were divided into the TAGMIC and non-TAGMIC group according to their treatment regime. We compared the 60-day, 6-month, and overall mortality and survival curves between groups. We also compared Barthel Index scores, Montreal Cognitive Assessment (MoCA) scores, and diffusion tensor imaging (DTI) results. Results: There was no significant difference in the 30-day mortality rate or Kaplan-Meier survival curve between groups. The 60-day, 6-month, and overall mortality rates in the TAGMIC group were significantly reduced (P = 0.043, P = 0.018, and P = 0.018, respectively) compared with the non-TAGMIC group (0, 0, 0 vs. 31.25, 37.5, 37.5%, respectively). The 60-day, 6-month, and overall Kaplan-Meier survival curves were significantly different between groups (P = 0.020, P = 0.009, P = 0.009, respectively). There was no significant difference in the Barthel Index scores of surviving patients. Among the five patients who underwent MoCA and DTI, four had a score of 0/5 for delayed recall (no cue), while the remaining patient had a score of 2/5. All five patients were able to achieve a score of 5/5 with classification and multiple-choice prompts, and had sparse or broken corpus callosum (or other) fibre bundles. Conclusion: TAGMIC treatment can reduce mortality due to severe Japanese encephalitis. The memory loss of surviving patients is mainly due to a disorder of the memory retrieval process, which may be related to the breakage of related fibre bundles.

Tie2-expressing monocytes as a novel angiogenesis-related cellular biomarker for non-small cell lung cancer.

To investigate the clinical value of Tie2-expressing monocytes (TEMs) in the early diagnosis of lung cancer and assess its correlation with angiogenesis, a total of 184 patients with non-small cell lung cancer (NSCLC), 101 patients with benign pulmonary disease (BPD), and 77 healthy controls were enrolled in our study. The distribution of TEMs in lung tissue was determined by immunofluorescence staining. Lung microvascular density was assessed by immunohistochemical staining. Receiver-operating characteristic (ROC) curve analysis was performed to assess the diagnostic value of TEM frequency. Patients with NSCLC were followed up for 26 months. We found that the TEM frequency in peripheral blood monocytes of patients with NSCLC was significantly greater than that in patients with BPD and healthy controls. TEM frequency showed a correlation with NSCLC recurrence. The majority of TEMs in tumor tissues were localized around blood vessels; tumoral TEM frequency showed a positive correlation with microvascular density. High percentage of TEMs in the peripheral blood was associated with poor overall survival. ROC curve analysis revealed the potential diagnostic value of circulating TEM frequency in NSCLC. Thus, we believe that TEM frequency is related to angiogenesis in tumor tissues and may serve as a diagnostic marker for NSCLC.

Overexpression of Egr2 and Egr4 protects rat brains against ischemic stroke by downregulating JNK signaling pathway.

OBJECTIVE: The purpose of this study was to investigate the effect of Egr2 and Egr4 upregulation on ischemic stroke recovery of rats. METHODS: In this study, Sprague Dawley (SD) rats assigned at random into control, sham and MCAO (middle cerebral artery occlusion) group were treated accordingly to build MCAO models. The neurological severity scores (NSS) test was applied to assess rats' behavior. Triphenyltetrazolium chloride (TTC) staining reflected infarct areas while Nissl staining revealed the number of neurons. Levels of pro-inflammatory cytokines (interleukin [IL]-1ß, IL-6 and tumor necrosis factor [TNF]-α) were judged by enzyme-linked immunosorbent assay (ELISA) in brain and serum tissues. We applied western blot to check the expression of Egr2, Egr4 and JNK/c-JUN (c-Jun N-terminal kinase) pathway. Further grouping of rats were based on various transfection, requiring control, sham, MCAO, MCAO + Egr2 cDNA (complementary DNA), MCAO + Egr4 cDNA, MCAO + Egr2 cDNA + Egr4 cDNA group to observe difference in MCAO recovery and JNK/c-JUN-pathway-related protein expression. RESULTS: Under successful modeling of MCAO, western blot results suggested down-regulation of Egr2 and Egr4 and overexpression of pro-inflammatory cytokines. The JNK/c-JUN pathway was activated. On upregulation of Egr2 and Egr4 in infarct areas, neurological function of SD rats recovered along with repressed JNK/c-JUN pathway activation and increased neuron number. CONCLUSION: Upregulation of Egr2 and Egr4 could demote the activation of JNK/c-JUN pathway and the expression of pro-inflammatory cytokines in MCAO rats, so that Egr2 and Egr4 might be potential targets for ischemic stroke in future.

Exploring relationships between first-line nurse manager's safety attitudes and safety factors in Henan, China.

AIM: To examine first-line nurse managers' perceptions of safety culture and explore relationships between their safety attitudes and safety factors in Henan Province, China. BACKGROUND: Health providers' perceptions of patient safety culture have been studied widely, but little is known about first-line nurse managers' safety attitudes. METHODS: A cross-sectional survey was conducted with a convenience sample of 823 first-line nurse managers in 216 hospitals across Henan Province, China. The Safety Attitudes Questionnaire (Chinese version) was distributed to first-line nurse managers during training meetings; responses were returned in a sealed envelope in person or by mail. ANOVAs were used to analyse the differences in Safety Attitudes Questionnaire (Chinese version) scores between first-line nurse managers' attitudes and safety factors. RESULTS: The mean scores across the six domains of Safety Attitudes Questionnaire (Chinese version) ranged from 56.6 to 79.4 on a 100-point scale. First-line nurse managers: ≥45 years of age perceived better safety climate (p < .05); those with higher professional ranks and medical centre positions reported higher mean scores for teamwork climate (p < .01) and stress recognition (p < .01); and those with baccalaureate degrees or higher had significantly higher mean scores for stress recognition (p < .01). CONCLUSION: First-line nurse managers' safety attitudes were not satisfactory and there is great potential to improve patient safety culture. Age, hospital level, educational background and professional rank are positively related to first-line nurse managers' attitudes. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital administrators and nurse directors should focus on the safety factors identified in this study and enact a variety of strategies to create a strong patient safety culture in China.

Sex-based differences in outcomes after severe injury: an analysis of blunt trauma patients in China.

BACKGROUND: Experimental research suggests that females have a higher survival rate after trauma, although this claim is controversial. This study sought to determine the role of sex on mortality among trauma patients in China. METHODS: The study enrolled 1789 trauma patients who visited the Emergency Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University during 2015 and 2016. A retrospective data analysis was performed to determine sex-based differences after blunt trauma. Patients were stratified by age and injury severity (using the Injury Severity Score). Multiple logistic regression was used to analyze the association between sex and post-injury complications and mortality. RESULTS: Female trauma patients experienced a significantly lower risk of mortality than males (odds ratio, 0.931; 95% confidence interval, 0.883-0.982). This survival advantage of females was particularly notable in the 'younger than 45 years' age group. Sex-based differences were also found in the occurrence of life-threatening complications after trauma. CONCLUSION: This study demonstrated that females are more likely to survival after severe blunt trauma and also have less inpatient complications than men, suggesting an important role for sex hormones after severe traumatic injury.

Survey and Risk Factors for Lower Urinary Tract Storage Symptoms in Middle-Aged and Older Stroke Patients in Urban China.

OBJECTIVES: To evaluate the prevalence and associated risk factors of lower urinary tract symptoms (LUTS) in people with stroke. This was the first study that systematically surveyed the risk factors for LUTS in people with various lengths of stroke history in urban Chinese communities. METHODS: A community-based, cross-sectional study was performed on 1404 residents aged over 40 years, randomly selected in the urban area of Zhengzhou, China. A questionnaire including the subjects' general health information, sociodemographic background, medical history, and the overactive bladder symptom score (OABSS) was filled by the subjects on site. RESULTS: Data from 706 (63.8.9 ± 8.9 years old) stroke subjects and 698 non-stroke subjects were analyzed. The prevalence of LUTS in stroke subjects was 62.6%, significantly higher than non-stroke subjects. The prevalence in men was higher than women (P < 0.01). The stroke subjects with diabetes mellitus had higher odds for LUTS than those without diabetes (P < 0.05). The prevalence of LUTS was also significantly correlated with increasing age, high educational level, living alone, snoring, hypertension and coronary heart diseases (P < 0.01). CONCLUSIONS: Our study identified not only putative risk factors for LUTS in middle-aged and elderly stroke patients, but genuine factors including snoring, living environment and educational background that increased the odds of storage symptoms as well. We identified that regular exercise and living with their children were protective factors for storage symptoms in stroke patients.

Restless legs syndrome and hypertension in Chinese pregnant women.

Hypertension is a common complication of pregnancy, and studies show that pregnant women are more likely to suffer from restless legs syndrome (RLS). Pregnant women with hypertension and RLS often experience disrupted sleep patterns because of activation of the nervous system. The present study aimed to clarify the relationship between hypertension and RLS in pregnant women, and their impact on sleep. We enrolled 3,781 pregnant women who were admitted at our hospital for delivery between May 2011 and May 2014. The face-to-face questionnaire used to gather data included the International RLS Study Group criteria for diagnosis, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and hypertension diagnosis. Depending on the time of occurrence of hypertension, it was divided into two different types: pregnancy-induced hypertension and chronic hypertension in pregnancy. Out of 3,781 patients, 453 fulfilled the diagnostic criteria for RLS and 486 met the diagnostic criteria for hypertension. Among patients with RLS, prophylactic iron supplementation was less frequently taken during pregnancy. Pregnancy-induced hypertension, rather than chronic hypertension in pregnancy, was found to be more frequent in patients with RLS; pregnant women with RLS had higher PSQI and ESS scores than pregnant controls. In our study, RLS was frequent in pregnant women, especially in those without prophylactic iron supplementation. Patients with RLS described more serious sleep disruption and excessive daytime sleepiness (EDS). In addition, pregnancy-induced hypertension was more common in patients with RLS.

Restless legs syndrome among pregnant women in China: prevalence and risk factors.

BACKGROUND: The goal of this study was to identify the prevalence and clinical correlates and severity of restless legs syndrome (RLS) among pregnant women in mainland China. METHODS: This cross-sectional study enrolled 1584 women (18-40 years old) who came to a prenatal outpatient clinic to consult an obstetrician. Pregnant women were studied in each trimester, and assessments included interviews about RLS symptoms and related questions. Standardized questionnaires include the International Restless Syndrome Scale and the Pittsburgh Sleep Quality Questionnaire. Blood tests included levels of hemoglobin and mean corpuscular volume. RESULTS: RLS was diagnosed in 177 of 1584 women (11.2%); 4.2% were categorized as having pre-existing RLS and 54.8% reported onset of RLS symptoms after the 24th week. Multivariate analysis revealed that anemia was positively correlated with RLS. For the participants who first experienced RLS in pregnancy, RLS severity in the third trimester was more severe when compared with the first and second trimesters. Sleep disorders occurred more frequently in the third trimester. CONCLUSIONS: In our study, RLS was frequent in pregnant Chinese women, and anemia was identified as an independent predictor of the disease. Further, most participants reported their symptoms during the third trimester, and the severity of RLS and sleep disorders of participants was more prominent in the third trimester.

Urine flow acceleration is superior to Qmax in diagnosing BOO in patients with BPH.

We performed a retrospective, case-control study to evaluate whether the urine flow acceleration (UFA, mL/s(2)) is superior to maximum uroflow (Qmax, mL/s) in diagnosing bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH). In this study, a total of 50 men with BPH (age: 58±12.5 years) and 50 controls (age: 59±13.0 years) were included. A pressure-flow study was used to determine the presence of BOO according to the recommendations of Incontinence Control Society (ICS). The results showed that the UFA and Qmax in BPH group were much lower than those in the control group [(2.05±0.85) vs. (4.60±1.25) mL/s(2) and (8.50±1.05) vs. (13.00±3.35) mL/s] (P<0.001). According to the criteria (UFA<2.05 mL/s(2), Qmax<10 mL/s), the sensitivity and specificity of UFA vs. Qmax in diagnosing BOO were 88%, 75% vs. 81%, 63%. UFA vs. Omax, when compared with the results of P-Q chart (the kappa values in corresponding analysis), was 0.55 vs. 0.35. The prostate volume, post void residual and detrusor pressure at Qmax between the two groups were 28.6±9.8 vs. 24.2±7.6 mL, 60.4±1.4 vs. 21.3±2.5 mL and 56.6±8.3 vs. 21.7±6.1 cmH2O, respectively (P<0.05). It was concluded that the UFA is a useful urodynamic parameter, and is superior to Qmax in diagnosing BOO in patients with BPH.

Prediction of the outcome of antenatal hydronephrosis: significance of urinary EGF.

BACKGROUND: Down-regulation of epidermal growth factor (EGF) in the renal parenchyma has been demonstrated in children who underwent pyeloplasty due to ureteropelvic junction obstruction (UPJO). Urine levels of EGF were confirmed to parallel this finding before and after surgery. The aim of our study was to evaluate the relationship between urinary EGF (uEGF) concentrations and Society of Fetal Urology (SFU) high-grade hydronephrosis in infants presenting unilateral antenatal hydronephrosis (ANH). METHODS: This was a prospective study involving 45 infants (33 in the observational group, 12 in the surgical group) who presented with unilateral ANH. Postnatal evaluation included a clinical examination, renal ultrasonography, and voiding cystourethrography. Diuretic renal scans were performed in infants with an initial SFU grade 3 or 4 hydronephrosis or increasing hydronephrosis during follow-up. Pyeloplasty was performed when a well-tempered renogram showed an obstructive drainage curve with a half-life of >20 min and/or an obstructive washout curve pattern during the diuretic phase. We studied the longitudinal changes in SFU hydronephrosis grade and uEGF in each group and compared concentration levels at three time points in both groups. The enzyme-linked immunosorbent assay (ELISA) method was used to measure EGF concentrations in the urine. The results were normalized with urinary creatinine (Cr). RESULTS: During the first 6 months, from 6 to 12 months, and in the second year of life, median SFU hydronephrosis grade and uEGF levels were 2, 2 (p = 0.015), and 1 (p < 0.01), and 50, 59 (p = 0.015), and 69.5 ng/mg Cr (p < 0.01), respectively, in the observational group. In the first 6 months, preoperatively and at 3-12 months postoperatively, the median SFU hydronephrosis grade and uEGF levels were 4, 4, and 3 (p > 0.05), and 38, 46, (p > 0.05), and 55 ng/mg Cr (p < 0.01), respectively, in the surgical group. uEGF levels in the first 6 months of life were significantly lower in the surgical group than in the observational group (p < 0.01). Patients in the observational group with SFU grade 3-4 hydronephrosis showed higher uEGF levels than those in the surgical group with SFU grade 3-4 in (p = 0.048). CONCLUSIONS: Urinary EGF changes over time are associated with inverse changes in SFU hydronephrosis grade, which suggests a role for uEGF as a predictive marker of worsening hydronephrosis grades in infants with ANH. uEGF in the first 6 months of life may predict the need for surgery in infants with ANH.