Rationale for immune checkpoint inhibitors plus targeted therapy for advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is a frequent urological malignancy characterized by a high rate of metastasis and lethality. The treatment strategy for advanced RCC has moved through multiple iterations over the past three decades. Initially, cytokine treatment was the only systemic treatment option for patients with RCC. With the development of medicine, antiangiogenic agents targeting vascular endothelial growth factor and mammalian target of rapamycin and immunotherapy, immune checkpoint inhibitors (ICIs) have emerged and received several achievements in the therapeutics of advanced RCC. However, ICIs have still not brought completely satisfactory results due to drug resistance and undesirable side effects. For the past years, the interests form researchers have been attracted by the combination of ICIs and targeted therapy for advanced RCC and the angiogenesis and immunogenic tumor microenvironmental variations in RCC. Therefore, we emphasize the potential principle and the clinical progress of ICIs combined with targeted treatment of advanced RCC, and summarize the future direction.

CD73 as a T cell dysfunction marker predicting cardiovascular and infection events in patients undergoing hemodialysis.

BACKGROUND: T cell dysfunction observed in patients undergoing hemodialysis (HD) has been linked to an extremely high morbidity of cardiovascular events (CVEs) and infections. The cell-surface 5'-nucleotidase CD73 sets the balance between pro-inflammatory nucleotides and anti-inflammatory adenosine. METHODS: A total of 395 patients who had been receiving HD for at least six months were evaluated for proportions of CD73+ cells in both the CD4+ T cell and CD8+ T cell compartment and followed for one year to document CVEs and infections. Differences in the proportions of CD73-expressingT cells between healthy controls and patients undergoing HD were compared. The relationship between CD73+ T cells and clinical outcomes was analyzed using the Kaplan-Meier curve and Cox regression. RESULTS: HD was significantly related to a lower fraction of CD4+CD73+ T cells. In patients on HD, lower proportions of CD4+ CD73+T cells and CD8+ CD73+T cells were both associated with systemic inflammation and T cell terminal differentiation. More importantly, a lower CD4+CD73+T cell ratio independently predicted CVEs and infection in these patients. CONCLUSION: We identified CD73 as a T cell dysfunction marker predicting cardiovascular and infection events in patients undergoing HD, which provides a potential target in future studies of uremia-related immune dysfunction.

The Association Between Serum Glutathione Peroxidase-3 Concentration and Risk of Acute Kidney Injury After Cardiac Surgery: A Nested Case-Control Study.

Oxidative stress has an integral role in the pathophysiology of cardiac surgery-associated acute kidney injury (CSA-AKI). Glutathione peroxidase 3 (GPx3) is an important antioxidant enzyme in circulation and is mainly secreted by the kidney. This study aimed to evaluate the relation between GPx3 protein and CSA-AKI. This study is a nested case-control study in Zhongshan Hospital affiliated with Fudan University. We examined serum samples from 80 CSA-AKI patients and 80 age- and gender-matched non-AKI patients who underwent cardiac surgery. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) 2012 criteria. We measured serum GPx3 concentration using the enzyme-linked immunosorbent assay. GPx3 ratio is the ratio of preoperative and 6 hours postoperative of GPx3 protein concentration. We applied dose-response relation analyses to odds ratio in different GPx3 ratio levels and integrated it into the logistic model to predict the risk of AKI. The receiver operating characteristic curve and area under the curve (AUC) was used to assess the prediction models. Postoperative serum GPx3 concentrations were significantly lower in the AKI group compared with the non-AKI group (1.78 ± 0.33 vs 2.03 ± 0.27, p <0.001). Malondialdehyde was higher in the AKI than in the non-AKI group (17.74 ± 8.65 vs 7.48 ± 4.59, p <0.001). The AKI risk increased in a dose-dependent manner, which was flat in the first half of the GPx3 ratio and then tended to be faster. The peaking odds ratio of CSA-AKI was 2.615 at the GPx3 ratio of 1.21 to 1.40. The AUC value to predict CSA-AKI only included the GPx3 ratio was 72.3%. After gradually integrating other covariates (body mass index, aortic crossclamp time, and cardiopulmonary bypass), the model showed an AUC of 82.6%. The serum GPx3 concentration was significantly lower in the CSA-AKI group. GPx3 ratio has a good predictive value for CSA-AKI, which may be a potential early diagnostic marker for AKI.

Weekend effect on the incidence and outcomes of cardiac surgery associated - acute kidney injury.

BACKGROUND: The effects of surgical day (workdays or weekends) on occurrence and outcome of cardiac surgery associated -acute kidney injury (CSA-AKI) remains unclear. This study aimed to compare the incidence and short-term outcomes of CSA-AKI in patients undergoing surgery on workdays and weekends. MATERIALS AND METHODS: Patients who underwent cardiac surgery from July 2020 to December 2020 were retrospectively enrolled in this study. These patients were divided into a weekend group and workday group. The primary endpoint was the incidence of CSA-AKI. The secondary endpoints included renal function recovery and in-hospital mortality. The logistic regression model was used to explore the risk factors for CSA-AKI. Stratification analysis was performed to estimate the association between CSA-AKI and weekend surgery stratified by emergency surgery. RESULTS: A total of 1974 patients undergoing cardiac surgery were enrolled. The incidence of CSA-AKI in the weekend group was significantly higher than that in the workday group (42.8% vs. 34.7%, P = 0.038). Further analysis of patients with CSA-AKI showed that there was no difference in renal function recovery between the workday AKI group and weekend AKI group. There was no difference in in-hospital mortality between the weekend group and workday group (3.6% vs. 2.4%, P = 0.327); however, the in-hospital mortality of the weekend AKI group was significantly higher than that of the workday AKI group (8.5% vs. 2.9%, P = 0.014). Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. The multiplicative model showed an interaction between weekend surgery and emergency surgery; weekend surgery was related to an increased risk of AKI among patients undergoing emergency surgery [adjusted OR (95% CI): 1.96 (1.012-8.128)]. CONCLUSIONS: The incidence of CSA-AKI in patients undergoing cardiac surgery on weekends was significantly higher compared to that in patients undergoing cardiac surgery on workdays. Weekend surgery did not affect the in-hospital mortality of all patients but significantly increased the mortality of AKI patients. Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. Weekend emergency surgery significantly increased the risk of CSA-AKI.

A primary pediatric acute myelomonocytic leukemia with t(3;21)(q26;q22): A case report.

RATIONALE: The rare t(3;21)(q26;q22) translocation results in gene fusion and generates multiple fusion transcripts, which are typically associated with therapy-related myelodysplastic syndrome, acute myeloid leukemia, and chronic myelogenous leukemia. Here, we report a rare case of de novo acute myelomonocytic leukemia in a young child with t(3;21)(q26;q22). PATIENT CONCERNS: A 2-and-a-half-year-old female patient presented with abdominal pain, cough, paleness, and fever for 3 weeks, without any history of malignant diseases. DIAGNOSES: Chest computed tomography revealed pneumonia. Bone marrow smear confirmed acute myelomonocytic leukemia. Cytogenetic analysis and Sanger sequencing identified RUNX1-MECOM and RUNX1-RPL22 fusion genes as a result of t(3;21)(q26;q22). INTERVENTIONS: The patient received 3 courses of chemotherapy, but bone marrow smear examination showed no remission. According to the wishes of the patient family, the allogeneic hematopoietic stem cell transplantation (Allo-HSCT) was chosen. OUTCOMES: The patient did not experience any adverse reactions after Allo-HSCT. The red blood cells and platelets increased without transfusion. The pneumonia recovered after antibiotic treatment. LESSONS: The patient recovered well after Allo-HSCT. Therefore, for patients with RUNX1-MECOM and RUNX1-RPL22 fusion genes, transplantation may be a good choice when chemotherapy is not effective.

Molecular epidemiology and clinical characteristics of enteroviruses associated HFMD in Chengdu, China, 2013-2022.

OBJECTIVES: This study aims to investigate molecular epidemiology and clinical characteristics of enterovirus associated hand-foot-mouth disease (HFMD) in Chengdu, China, 2013-2022. Monitoring the molecular epidemiology and clinical features of HFMD for up to 10 years may provide some ideas for future protection and control measures. METHODS: We conducted a retrospective analysis of the medical records of all patients with laboratory-confirmed HFMD-related enterovirus infection at the West China Second University Hospital from January 2013 to December 2022. We described the characteristics in serotype, age, sex distribution and hospitalization of enterovirus infection cases using data analysis and graphic description. RESULTS: A total of 29,861 laboratory-confirmed cases of HFMD-related enterovirus infection were reported from 2013 to 2022. There was a significant reduction in the number and proportion of EV-A71 cases after 2016, from 1713 cases (13.60%) in 2013-2015 to 150 cases (1.83%) in 2017-2019. During the COVID-19 pandemic, EV-A71 cases even disappeared. The proportion of CV-A16 cases decreased from 13.96% in 2013-2015 to 10.84% in 2017-2019 and then to 4.54% in 2020-2022. Other (non-EV-A71 and non-CV-A16) serotypes accounted for 95.45% during 2020-2022, with CV-A6 accounting for 50.39% and CV-A10 accounting for 10.81%. Thus, CV-A6 and CV-A10 became the main prevalent serotypes. Furthermore, There was no significant difference in the enterovirus prevalence rate between males and females. The hospitalization rate of EV-A71 patients was higher that of other serotypes. In general, the proportion of HFMD hospitalizations caused by other pathogens except for EV-A71, CV-A16, CV-A10 and CV-A16 was second only to that caused by EV-A71. The proportion of children over 4 years old infected with enterovirus increased. CONCLUSION: The incidence of HFMD associated with enterovirus infection has decreased significantly and CV-A6 has been the main pathogen of HFMD in Chengdu area in recent years. The potential for additional hospitalizations for other untested enterovirus serotypes suggested that attention should also be paid to the harms of infections with unknown enterovirus serotypes. Children with HFMD were older. The development of new diagnostic reagents and vaccines may play an important role in the prevention and control of enterovirus infection.

Revealing the Influence of SiC Particle Size on the Hot Workability of SiCp/6013 Aluminum Matrix Composites.

SiC particle (SiCp) size has been found to significantly influence the hot workability of particle-reinforced aluminum matrix composites (AMC). In this work, therefore, three types of SiCp/6013 composites with different SiCp sizes (0.7, 5 and 15 µm) were prepared and then subjected to isothermal hot compression tests. In addition, constitutive analysis, processing maps and microstructural characterizations were used to reveal the influence of SiCp size on the hot workability of SiCp/6013 composite. The results showed that the values of hot deformation activation energy Q increased with decreasing SiCp size. Specifically, at lower temperatures (e.g., 350 and 400 °C), the highest peak stress was shown in the AMC with SiCp size of 0.7 µm (AMC-0.7), while in the AMC with SiCp size of 5 µm (AMC-5) at higher temperatures (e.g., 450 and 500 °C). This is because a finer SiCp size would lead to stronger dislocation pinning and grain refinement strengthening effects, and such effects would be weakened at higher temperatures. Further, dynamic softening mechanisms were found to transform from dynamic recovery to dynamic recrystallization with increasing SiCp size, and the dynamic recrystallization occurred more easily at higher temperatures and lower strain rates. Consequently, the instability zones of the composites are all mainly located in the deformation region with lower temperature and higher strain rate, and smaller SiCp results in larger instability zones.

Leishmania donovani visceral leishmaniasis diagnosed by metagenomics next-generation sequencing in an infant with acute lymphoblastic leukemia: a case report.

Background: Visceral leishmaniasis (VL) is a neglected vector-borne tropical disease caused by Leishmania donovani (L. donovani) and Leishmania infantum (L. infantum). Due to the very small dimensions of the protozoa impounded within blood cells and reticuloendothelial structure, diagnosing VL remains challenging. Case presentation: Herein, we reported a case of VL in a 17-month-old boy with acute lymphoblastic leukemia (ALL). The patient was admitted to West China Second University Hospital, Sichuan University, due to repeated fever after chemotherapy. After admission, chemotherapy-related bone marrow suppression and infection were suspected based on clinical symptoms and laboratory test results. However, there was no growth in the conventional peripheral blood culture, and the patient was unresponsive to routine antibiotics. Metagenomics next-generation sequencing (mNGS) of peripheral blood identified 196123 L. donovani reads, followed by Leishmania spp amastigotes using cytomorphology examination of the bone marrow specimen. The patient was given pentavalent antimonials as parasite-resistant therapy for 10 days. After the initial treatment, 356 L. donovani reads were still found in peripheral blood by mNGS. Subsequently, the anti-leishmanial drug amphotericin B was administrated as rescue therapy, and the patient was discharged after a clinical cure. Conclusion: Our results indicated that leishmaniasis still exists in China. Unbiased mNGS provided a clinically actionable diagnosis of a specific infectious disease from an uncommon pathogen that eluded conventional testing.

Effect of angiography timing on acute kidney injury after cardiac surgery in patients with preoperative renal dysfunction.

BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) is one of the common complications of cardiac surgery. Preoperative angiography helps assess heart disease but may increase the risk of AKI. Although more and more patients with preoperative renal dysfunction can undergo cardiac surgery with the advances in surgical techniques, there is little research on the effect of angiography on postoperative AKI in these patients. This study investigates whether angiography increases the risk of AKI after cardiac surgery in patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2). METHODS: Patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2) who underwent angiography and cardiac surgery successively from January 2015 to December 2020 were retrospectively enrolled in this study. The primary outcome was postoperative AKI, defined as the Kidney Disease: Improving Global Outcomes Definition and Staging (KDIGO) criteria. Univariate analysis and multivariate regression were performed to identify the association between angiography timing and AKI. RESULTS: A total of 888 consecutive eligible patients with preoperative renal dysfunction (15 ≤ eGFR < 60 ml/min/1.73m2) were enrolled in this study. The incidence of AKI was 48.31%. Male (OR = 1.903), the interval between angiography and surgery (0-2d OR = 2.161; 3-6d OR = 3.291), cross-clamp duration (OR = 1.009), were identified as predictors for AKI. The interval between angiography and surgery was also associated with AKI in the patients with 15 ≤ eGFR < 30ml/min/1.73m2 (0-2d OR = 4.826; 3-6d OR = 5.252), 30 ≤ eGFR < 45 ml/min/1.73m2 (0-2d OR = 2.952; 3-6d OR = 3.677), but not associated with AKI in patients with 45 ≤ eGFR < 60 ml/min/1.73m2. CONCLUSIONS: In patients with preoperative renal dysfunction, the interval between angiography and cardiac surgery (0-2d and 3-6d) was associated with AKI. For patients with poorer preoperative renal function, the interval between angiography and cardiac surgery is of great concern.

Proteinuria is a risk factor for acute kidney injury after cardiac surgery in patients with stages 3-4 chronic kidney disease: a case control study.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery, and preoperative renal dysfunction is an important risk factor. Proteinuria indicates renal structural damage, but there are few studies on proteinuria and the risk of AKI after cardiac surgery in patients with renal dysfunction. This study aimed to elucidate whether proteinuria can predict AKI after cardiac surgery in patients with renal dysfunction. METHODS: Patients with stages 3-4 chronic kidney disease (CKD) who underwent cardiac surgery were included in this retrospective study. AKI was defined according to the KDIGO criteria. The association between proteinuria and AKI in patients with CKD stages 3-4 was investigated. RESULTS: The incidence of AKI in the entire cohort (n = 1546) was 53.55%. The in-hospital mortality of patients with was higher than patients without AKI (AKI vs. no AKI, 4.7 vs. 0.8%, P < 0.001). Multivariate logistic regression analysis showed that proteinuria was an independent risk factor for AKI (trace to 1+ OR 2.37; 2+ -3+ OR 5.16) and AKI requiring renal replacement therapy (AKI-RRT) (trace to 1+ OR 3.64; 2+-3+ OR 5.71). Mild proteinuria (trace to 1+ OR 2.59) was also an independent risk factor for in-hospital death. In patients with diabetes mellitus, mild proteinuria (OR 1.925), instead of severe proteinuria (2-3+), was a risk factor of AKI in patients with kidney dysfunction and diabetes. CONCLUSIONS: In the population of patients with renal dysfunction, the incidence of AKI was high, which significantly compromised renal and overall prognosis. As a simple and inexpensive routine test, preoperative proteinuria still has value in predicting AKI in patients with impaired renal function.

Hot Workability of the Multi-Size SiC Particle-Reinforced 6013 Aluminum Matrix Composites.

The size and distribution of ceramic particles in aluminum matrix composites have been reported to remarkably influence their properties. For a single ceramic particle, the particle size is too small and prone to agglomeration, which makes the mechanical properties of the composites worse. When the ceramic particle size is too large, the particles and alloy at the interface are not firmly bonded, and the effect of dispersion distribution is not achieved, which will also reduce the mechanical properties of the composites. The multi-size ceramic particles are expected to improve this situation, while their effect on hot workability is less studied. In this study, the hot deformation behavior, constitutive model, processing map and SEM microstructure were investigated to evaluate the hot workability of multi-size SiC particle-reinforced 6013 aluminum matrix composites. The results showed that the increased deformation temperature and decreased strain rate could decrease flow stresses. The flow stress behaviors of the composites can be described by the sine-hyperbolic Arrhenius equation with the deformation activation energy of Q = 205.863 kJ/mol. The constitutive equation of the composites is ε ˙=3.11592×1013sinh0.024909σ4.12413exp−205863RT. Then, the hot processing map of the SiCp/6013 composites was constructed and verified by SEM observations. The rheological instability zone was in the region of a high strain rate. The optimal processing zone for composites was 450~500 °C and 0.03~0.25 s−1. In addition, the strain level was found to increase both the Q value and the area of the instability zone.

Risk Factors and Prognosis of Acute Kidney Injury after Cardiac Surgery in Patients with Chronic Kidney Disease.

INTRODUCTION: Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most prevalent complications of cardiac surgery, while the renal and overall prognoses of chronic kidney disease (CKD) patients with CSA-AKI are extremely poor. However, there is little published information on the occurrence of CSA-AKI in patients with CKD. The purpose of this study was to investigate the risk factors and prognostic factors of cardiac surgery-related AKI in patients with CKD. METHODS: A retrospective study was performed on CKD patients who underwent cardiac surgery at a tertiary referral teaching hospital. CSA-AKI was defined based on the KDIGO criteria. The risk factors for CSA-AKI and the factors affecting renal function recovery at discharge or death in patients with AKI were investigated. RESULTS: Among 1638 CKD patients enrolled, the incidence of CSA-AKI was 50.55%. AKI patients' in-hospital mortality was higher than patients without AKI (AKI vs. no AKI, 4.7 vs. 0.9%, p < 0.001). Multivariate logistic regression analysis showed that male (odds ratio [OR] 1.479), preoperative hypertension (OR 1.548), preoperative hemoglobin <110 g/L (OR 2.389), and aortic clamping time >58 min (OR 1.567) were independent risk factors for AKI after cardiac surgery in patients with CKD. Factors affecting renal function recovery of AKI patients included preoperative diabetes mellitus (OR 0.306), hyperchloremia (OR 0.927), estimate of the glomerular filtration rate (OR 1.034), and AKI progression. Compared with patients with AKI stage 1, the rate of renal function recovery in patients with AKI stage 2 and stage 3 was reduced by 78.9% and 82.3%, respectively. CONCLUSIONS: In the population of patients with CKD, the incidence of CSA-AKI was high, which significantly affected renal and overall prognosis. The prompt intervention of modifiable factors may help improve the prognosis of patients with CKD.

Information fields of written texts protect cells from oxidative damage and accelerate repair.

OBJECTIVE: Written words demonstrated specific effects on biochemical measures and cell growth in cultured mammalian cells in previous study. We examined the protection and reparative effects of Chinese texts with positive meaning and the word "Buddha" on oxidative-damaged cells, with the goal of exploring the therapeutic effect of such characters. METHODS: The human embryonic kidney cell line HEK293T was utilized, with the oxidative- damaged cell model produced by hydrogen peroxide (H2O2). Double-blind experiments were set up to ensure all operators involved in the experiments did not know the contents of the texts in envelopes. Petri-dishes (9 plates) containing oxidative-damaged cells were selected randomly for three controls, three treatments by texts with positive meaning, and another three treatment by the word "Buddha". Cells were sub-sampled at 3 h and 24 h to examine growth and mitochondrial functions. All data are expressed relative to the controls. RESULTS: Compared with the control group, mitochondrial functions were enhanced as evidenced by increased adenosine triphosphate (ATP) levels, accompanied by the significant improvement in cell growth rate for the groups treated by positive texts and the word "Buddha". Reactive oxygen species (ROS) levels were decreased significantly in positive texts treatment, which suggested that the antioxidant capacity of cells was also improved. CONCLUSIONS: This study revealed that certain texts can potentially offer protection and accelerate the cellular repair for oxidative-damaged cells.

Effect of Grain Size on the Plastic Deformation Behaviors of a Fe-18Mn-1.3Al-0.6C Austenitic Steel.

Grain size is a microscopic parameter that has a significant impact on the macroscopic deformation behavior and mechanical properties of twinning induced plasticity (TWIP) steels. In this study, Fe-18Mn-1.3Al-0.6C steel specimens with different grain sizes were first obtained by combining cold rolling and annealing processes. Then the influence of grain size on the plastic deformation mechanisms was investigated by mechanical testing, X-ray diffraction-based line profile analysis, and electron backscatter diffraction. The experimental results showed that the larger grain size could effectively promote twinning during plastic straining, produce an obvious TWIP effect, and suppress the rate of dislocation proliferation. The continuous contribution of dislocation strengthening and twinning functions led to a long plateau in the work-hardening rate curve, and increased the work-hardening index and work-hardening ability. At the same time, the strain could be uniformly distributed at the grain boundaries and twin boundaries inside the grain, which effectively relieved the stress concentration at the grain boundaries and improved the plasticity of deformed samples.

Mycoplasma genitalium and Chlamydia trachomatis infection among women in Southwest China: a retrospective study.

Mycoplasma genitalium (MG) and Chlamydia trachomatis (CT) are the most common sexually transmitted pathogens, which can cause cervicitis, pelvic inflammation and infertility in female. In the present study, we collected the basic information, clinical results of leucorrhoea and human papillomavirus (HPV) infection of patients, who were involved in both MG and CT RNA detection in West China Second Hospital of Sichuan University from January 2019 to April 2021, ranging from 18 to 50 years old. The results showed that the infection frequencies of MG and CT were 2.6% and 6.5%, respectively. The infection rate of CT in gynaecological patients was significantly higher than that of MG (P < 0.001). Moreover, patients with CT infection often had symptoms of gynaecological diseases, while patients with MG infection remain often asymptomatic. By exploring the connection between MG or CT infection and vaginal secretions, we found that the infection of MG or CT promoted to the increase of vaginal leukocytes, and CT infection exacerbated the decrease of the number of Lactobacillus in the vagina. Further analysis suggested that independent infection and co-infection of MG or CT resulted in abnormal vaginal secretion, affecting the stability of vaginal environment, which may induce vaginal diseases. Unexpectedly, our study found no association between MG or CT infection and high-risk HPV infection. In conclusion, our study explored the infection of MG and CT among women in Southwest China for the first time, and revealed that the infection of MG or CT would affect the homeostasis of vaginal environment, which laid a foundation for the clinical diagnosis and treatment of MG and CT infection.

Effects of different music on HEK293T cell growth and mitochondrial functions.

BACKGROUND: Mitochondria are considered a portal to receive, process and integrate external energy and information to maintain cellular homeostasis. Previous studies demonstrated that mitochondrial function and antioxidant capacity of in-vitro cultured mammalian cells is modified by different energetic stimuli including electromagnetic energy, acoustic energy, external Qi and subtle energy emitted by written texts in relatively short time frames. Thus, individual cells can act as a rapid and sensitive biological sensor and act as a platform to evaluate and understand the subtle effect of different biophysical stimuli. Regarding acoustic energy, several different types of music have been reported to produce beneficial effects on human health. OBJECTIVE: To compare eastern and western music styles on cell function at the biochemical level to understand the underlying mechanisms involved. Methods In this study, we compared the effects of Chinese five-element music with two types of western music (heavy-metal and classical) on mitochondrial function, oxidative capacity and growth using HEK293T cells (human embryonic kidney cells). RESULTS: Unlike rock and classical music, exposing cells to five-element music produced several beneficial physiological effects, including statistically significant increases in the production of adenosine triphosphate (ATP) by 17%, glutathione (GSH) by 21% and cell growth rates (14%), as well as a significant reduction in the reactive oxygen species (ROS) by 13%. For the group treated with classical music, there was only a trend toward increased GSH (8%), although the increased growth rates (14%) did reach significance. In sharp contrast, the cells treated with heavy-metal music responded with an opposite and significant 16% increase in ROS and a significant 11% reduction in cell viability. CONCLUSIONS: This study revealed the dramatically different and even opposite effects of different styles of music on specific biochemical measures in cultured human cells. These results help explain the underlying biochemical mechanisms of the effects of the different types of music.

Improvement of cardiac function after coronary artery bypass grafting surgery reduces the risk of postoperative acute kidney injury.

BACKGROUND: Pre-existing renal dysfunction is an independent risk factor for cardiac surgery-associated acute kidney injury (AKI). We aimed to investigate whether the improvement of postoperative cardiac function after coronary artery bypass grafting (CABG) surgery would affect the risk of AKI in patients with different levels of baseline renal function. METHODS: Data were collected from patients who underwent CABG surgery from January 2018 to April 2019. Patients were divided into normal (GFR ≥ 90 ml/min/1.73 m2 ), non-CKD (60≤GFR < 90 ml/min/1.73 m2 ), and CKD (GFR < 60 ml/min/1.73 m2 ) groups. Improvement in cardiac function was defined as △LVEF (postoperative LVEF-preoperative LVEF) ≥ 10% preoperative LVEF. Patients were further divided into subgroups according to postoperative cardiac function improvement. RESULTS: A total of 1365 patients were enrolled, including 793 (58.1%) in the normal group, 476 (34.9%) in the non-CKD group, and 96 (7.0%) in the CKD group. The AKI incidence in the normal, non-CKD, and CKD groups was 22.2%, 28.4%, and 40.6%, respectively. Patients with improved cardiac function in the non-CKD and CKD groups had significantly lower AKI incidence than those without improved cardiac function (22.8% vs. 36.9%, p = .002% and 32.8% vs. 54.3%, p = .037, respectively). For non-CKD patients with improved cardiac function, the serum creatinine at discharge was significantly lower than its preoperative serum creatinine (0.8 ± 0.5 vs 1.2 ± 0.9 mg/dl, p = .002). Multivariate logistic regression analysis showed that the improvement in cardiac function could reduce the risk for postoperative AKI in non-CKD patients but not in CKD patients. CONCLUSIONS: For patients with renal dysfunction and mildly reduced eGFR (60≤GFR < 90 ml/min/1.73 m2 ), improved cardiac function after CABG surgery can reduce the serum creatinine level and reduce the risk for postoperative AKI.

Effects of hyperuricaemia, with the superposition of being overweight and hyperlipidaemia, on the incidence of acute kidney injury following cardiac surgery: a retrospective cohort study.

OBJECTIVES: Acute kidney injury (AKI) is a common complication of cardiac surgery. This study aimed to explore the effects of hyperuricaemia, being overweight and hyperlipidaemia as risk factors for AKI in patients following cardiac surgery (cardiac surgery-associated acute kidney injury (CSA-AKI)). DESIGN: Retrospective observational study. SETTING: University teaching, grade-A tertiary hospital in Shanghai, China. PARTICIPANTS: Patients who underwent cardiac surgery from July 2015 to December 2015 in Zhongshan Hospital, Fudan University. MAIN OUTCOME MEASURES: We investigated the effect of hyperuricaemia, in combination with being overweight and hyperlipidaemia, on the risk of CSA-AKI. RESULTS: A total of 1420 patients were enrolled. The AKI incidence in the highest uric acid group was 44.4%, while that in the lowest uric acid group was 28.5% (p<0.001). Patients in the higher uric acid quartiles were more likely to be overweight and hyperlipidaemic at the same time (p<0.001). Multivariate logistic regression analysis showed that hyperuricaemia was an independent risk factor for AKI (OR=1.237, 95% CI 1.095 to 1.885; p=0.009); being overweight or hyperlipidaemia alone was not an independent risk factor, but the combination of being overweight and hyperlipidaemia was (OR=1.544, 95% CI 1.059 to 2.252; p=0.024). In the final model, the OR value increased to 3.126 when hyperuricaemia was combined with being overweight and hyperlipidaemia, and the Hosmer-Lemeshow test showed that all three models fit well (p=0.433, 0.638 and 0.597, respectively). CONCLUSIONS: The combination of being overweight and having hyperlipidaemia was an independent risk factor, but being overweight or having hyperlipidaemia alone was not. The combination of hyperuricaemia, being overweight and hyperlipidaemia further increased the risk of CSA-AKI.

Exogenous glutathione exerts a therapeutic effect in ischemic stroke rats by interacting with intrastriatal dopamine.

We previously showed that oral administration of exogenous glutathione (GSH) exerted a direct and/or indirect therapeutic effect on ischemic stroke rats, but the underlying mechanisms remain elusive. In the current study, we conducted a quantitative proteomic analysis to explore the pathways mediating the therapeutic effect of GSH in cerebral ischemia/reperfusion (I/R) model rats. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The rats were treated with GSH (250 mg/kg, ig) or levodopa (L-dopa, 100 mg/kg, ig) plus carbidopa (10 mg/kg, ig). Neurologic deficits were assessed, and the rats were sacrificed at 24 h after cerebral I/R surgery to measure brain infarct sizes. We conducted a proteomic analysis of the lesion side striatum samples and found that tyrosine metabolism and dopaminergic synapse were involved in the occurrence of cerebral stroke and the therapeutic effect of GSH. Western blot assay revealed that tyrosine hydroxylase (TH) mediated the occurrence of I/R-induced ischemic stroke and the therapeutic effect of GSH. We analyzed the regulation of GSH on endogenous small molecule metabolites and showed that exogenous GSH had the most significant effect on intrastriatal dopamine (DA) in I/R model rats by promoting its synthesis and inhibiting its degradation. To further explore whether DA-related alterations were potential targets of GSH, we investigated the therapeutic effect of DA accumulation on ischemic brain injury. The combined administration of the precursor drugs of DA (L-dopa and carbidopa) significantly ameliorated neurological deficits, reduced infarct size, and oxidative stress, and decreased pro-inflammatory cytokines levels in the striatum of I/R injury rats. More interestingly, exogenous L-dopa/carbidopa could also greatly enhance the exposure of intracerebral GSH by upregulating GSH synthetases and enhancing homocysteine (HCY) levels in the striatum. Thus, administration of exogenous GSH exerts a therapeutic effect on ischemic stroke by increasing intrastriatal DA, and the accumulated DA can, in turn, enhance the exposure of GSH and its related substances, thus promoting the therapeutic effect of GSH.

Effect of information fields from written texts on cell growth and mitochondrial functions in-vitro: An exploratory study.

OBJECTIVE: Mitochondria are considered a portal to receive, process and integrate external energy and information to maintain cellular homeostasis. We examined the effect of Chinese texts with positive and negative meaning on the growth and mitochondrial functions using a mouse kidney collecting duct cell line called M1 cells. METHODS: To avoid skewing the results due to differential handling of the cells or analyzing the results, we conducted experiments by keeping the texts and blanks covered in brown opaque envelopes, exposed the cells to randomly selected envelopes and examined the differences over time. All operators involved in the experiments did not know the contents of the envelopes until the end of the experiments, and all data are expressed relative to the controls. RESULTS: Cell growth rate was not affected for the group treated with positive information but was significantly reduced by 18% when treated with negative information. At the biochemical level, positive texts significantly increased whole cell adenosine triphosphate (ATP) and glutathione (GSH) by 22% and 21% respectively. CONCLUSIONS: This study for the first time demonstrated the effect of written words on specific biochemical measures in cultured mammalian cells.