Facile synthesis of MoS2@red phosphorus heterojunction for synergistically photodynamic and photothermal therapy of renal cell carcinoma.

The therapy of the clear cell renal cell carcinoma (ccRCC) is crucial for the human healthcare due to its easy metastasis and recurrence, as well as resistance to radiotherapy and chemotherapy. In this work, we propose the synthesis of MoS2@red phosphorus (MoS2@RP) heterojunction to induce synergistic photodynamic and photothermal therapy (PDT/PTT) of ccRCC. The MoS2@RP heterojunction exhibits enhanced spectra absorption in the NIR range and produce local heat-increasing under the NIR laser irradiation compared with pure MoS2 and RP. The high photocatalytic activity of the MoS2@RP heterojunction contributes to effective transferring of the photo-excited electrons from the RP to MoS2, which promotes the production of various types of radical oxygen species (ROS) to kill the ccRCC cells. After the NIR irradiation, the MoS2@RP can effectively induce the apoptosis in the ccRCC cells through localized hyperthermia and the generation of ROS, while exhibiting low cytotoxicity towards normal kidney cells. In comparison to MoS2, the MoS2@RP heterojunction shows an approximate increase of 22 % in the lethality rate of the ccRCC cells and no significant change in toxicity towards normal cells. Furthermore, the PDT/PTT treatment using the MoS2@RP heterojunction effectively eradicates a substantial number of deep-tissue ccRCC cells in vivo without causing significant damage to major organs. This study presents promising effect of the MoS2@RP heterojunction-based photo-responsive therapy for effective ccRCC treatment.

Vaporization phosphorization-mediated synthesis of phosphorus-doped TiO2 nanocomposites for combined photodynamic and photothermal therapy of renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a disease with high incidence and poor prognosis. The conventional treatment involves radiotherapy and chemotherapy, but chemotherapeutic agents are often associated with side effects, i.e., cytotoxicity to nontumor cells. Therefore, there is an urgent need for the development of novel therapeutic strategies for ccRCC. We synthesized spherical P/TiO2 nanoparticles (P/TiO2 NPs) by vaporization phosphorization (VP). X-ray photoelectron spectroscopy (XPS) and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS) analyses confirmed that the anatase TiO2 surface was successfully doped with phosphorus and produced a large number of oxygen vacancies (OV). Serving as a photosensitizer, P/TiO2 NPs not only extended the photoresponse range to the near-infrared II region (NIR II) but also introduced a donor energy level lower than the TiO2 conduction band, narrowing the band gap, which could facilitate the migration of photogenerated charges and trigger the synergistic treatment of photodynamic therapy (PDT) and photothermal therapy (PTT). During NIR irradiation in vitro, the P/TiO2 NPs generated local heat and various oxygen radicals, including 1O2, ˙O2-, H2O2, and ˙OH, which damaged the ccRCC cells. In vivo, administration of the P/TiO2 NPs + NIR reduced the tumor volume by 80%, and had the potential to inhibit tumor metastasis by suppressing intratumor neoangiogenesis. The P/TiO2 NPs showed superior safety and efficacy relative to the conventional chemotherapeutic agent used in ccRCC treatment. This study introduced an innovative paradigm for renal cancer treatment, highlighting the potential of P/TiO2 NPs as safe and effective nanomaterials and presenting a compelling new option for clinical applications in anticancer therapy.

Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway.

INTRODUCTION: Hexarelin exhibits significant protection against organ injury in models of ischemia/reperfusion (I/R)-induced injury (IRI). Nevertheless, the impact of Hexarelin on acute kidney injury (AKI) and its underlying mechanism remains unclear. In this study, we investigated the therapeutic potential of Hexarelin in I/R-induced AKI and elucidated its molecular mechanisms. METHODS: We assessed the protective effects of Hexarelin through both in vivo and in vitro experiments. In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 µg/kg/d for 7 days before being sacrificed 24 h post-IRI. Subsequently, kidney function, histology, and apoptosis were assessed. In vitro, hypoxia/reoxygenation (H/R)-induced HK-2 cell model was used to investigate the impact of Hexarelin on apoptosis in HK-2 cells. Then, we employed molecular docking using a pharmmapper server and autodock software to identify potential target proteins of Hexarelin. RESULTS: In this study, rats subjected to I/R developed severe kidney injury characterized by tubular necrosis, tubular dilatation, increased serum creatinine levels, and cell apoptosis. However, pretreatment with Hexarelin exhibited a protective effect by mitigating post-ischemic kidney pathological changes, improving renal function, and inhibiting apoptosis. This was achieved through the downregulation of conventional apoptosis-related genes, such as Caspase-3, Bax and Bad, and the upregulation of the anti-apoptotic protein Bcl-2. Consistent with the in vivo results, Hexarelin also reduced cell apoptosis in post-H/R HK-2 cells. Furthermore, our analysis using GSEA confirmed the essential role of the apoptosis pathway in I/R-induced AKI. Molecular docking revealed a strong binding affinity between Hexarelin and MDM2, suggesting the potential mechanism of Hexarelin's anti-apoptosis effect at least partially through its interaction with MDM2, a well-known negative regulator of apoptosis-related protein that of p53. To validate these findings, we evaluated the relative expression of MDM2 and p53 in I/R-induced AKI with or without Hexarelin pre-administration and observed a significant suppression of MDM2 and p53 by Hexarelin in both in vivo and in vitro experiments. CONCLUSION: Collectively, Hexarelin was identified as a promising medication in protecting apoptosis against I/R-induced AKI.

Amphiphilic chitosan/carboxymethyl gellan gum composite films enriched with mustard essential oil for mango preservation.

In this paper, amphiphilic chitosan and carboxymethyl modified gellan gum were synthesized to develop an active edible fresh-keeping material. The optimal weight ratio of CMCS-g-CA/CMGG was determined as 5:2 through the characterization of Fourier transform infrared (FT-IR), Thermogravimetric analysis (TGA), mechanical and barrier properties of the composite films. In addition, the water vapor permeability and oxygen permeability of CMCS-g-CA/CMGG composite films incorporated with mustard essential oil were all declined, and the antibacterial property of the composite film solutions against E. coli, S. aureus and Bacillus anthracis was distinctly improved with the increase of mustard essential oil (MEO) dosage. Furthermore, the CMCS-g-CA/CMGG + 2.0 µL/mL MEO composite film exhibited an effective preservation on mango fruits during 20 days of storage based on the characterization of surface appearance and quality indexes of fruits. Hence, the multifunctional CMCA-g-CA/CMGG/MEO composite films can be served as a prospective eco-friendly packaging material for fruit preservation.

Effects of different concentrations of intraluminal sodium chloride solution on intracavitary ECG used for arm infusion port implantation.

At present, there are few clinical studies on the application of high-concentration sodium chloride solutions in intracavitary ECG-guided catheter tip localization during the arm infusion port implantation. This study observed the effects of sodium chloride solutions with different concentrations on intracavitary ECG-guided arm infusion port implantation in the patients with cancer. The 657 patients receiving arm infusion port implantation in our hospital between January 2020 and August 2021 were randomly divided into 0.9% sodium chloride solution conduction group (group A), 5.45% sodium chloride solution conduction group (group B) and 10% sodium chloride solution conduction group (group C). The derived rate of stable intracavitary ECG, the occurrence rate of characteristic P wave, the time used for catheter tip localization and the optimal position rate of catheter tip were compared between the three groups. The derived rate of stable intracavitary ECG was significantly higher in the group B (97.78%) and group C (98.63%) than in the group A (93.90%) (all P < 0.05). The occurrence rate of characteristic P wave was also significantly higher in the group B (96.89%) and group C (97.72%) than in the group A (88.73%) (all P < 0.001). The time used for catheter tip localization was significantly shorter in the group B [(49.73 ± 8.15) s] and group C [(48.27 ± 8.61) s] than in the group A [(69.37 ± 19.99) s] (all P < 0.001). There was no significant difference in the optimal position rate of catheter tip among the three groups (P > 0.05). The 5.45% and 10% sodium chloride solutions are significantly superior comparing with 0.9% sodium chloride solution in the derived rate of stable intracavitary ECG, occurrence rate of characteristic P wave and time used for catheter tip localization, but there were no significant differences between 5.45 and 10% sodium chloride solutions. Moreover, the 5.45% sodium chloride solution is closer to physiological state comparing with 10% sodium chloride solution, so the 5.45% sodium chloride solution may be recommended for the intracavitary ECG-guided arm infusion port implantation.

[Scutellarin alleviates lipopolysaccharide-induced renal injury via mediating cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 expression to inhibit nuclear factor-κB signaling pathway].

OBJECTIVE: To explore the protective effect and mechanism of scutellarin (Scu) on sepsis associated-acute kidney injury (SA-AKI). METHODS: (1) In vivo experiment: 36 male C57BL/6 mice were divided into normal saline (NS) control group, lipopolysaccharide (LPS) induced SA-AKI model group (LPS group), 20 mg/kg Scu control group (Scu 20 control group), and 5, 10, 20 mg/kg Scu pretreatment groups by random number table with 6 mice in each group. The SA-AKI model was reproduced by intraperitoneal injection of 10 mg/kg LPS. The NS control group was injected with NS intraperitoneally. The Scu pretreatment groups were intraperitoneally injected with different doses of Scu every day before LPS injection for 1 week. Scu 20 control group was injected with 20 mg/kg Scu for 1 week. After 24 hours of LPS treatment, mice in each group were sacrificed, kidney tissues were collected, and kidney injury was detected by hematoxylin-eosin (HE) staining. Western blotting was used to detect the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway related molecules, apoptosis-related proteins and cysteine-rich protein 61-connective tissue growth factor-nephroblastoma overexpressed gene 1 (CCN1). (2) In vitro experiment: human renal tubular epithelial cell line HK-2 was cultured in vitro and used for experiment when the cells fused to 80%. In the cells without LPS treatment and after 100 g/L LPS treatment, pcDNA3.1-CCN1 and small interfering RNA (siRNA) CCN1 sequence were transfected to overexpress and inhibit CCN1 expression, respectively, to observe whether CCN1 was involved in NF-κB signaling pathway activation and apoptosis. In addition, 100g/L LPS and 20 µmol/L Scu were added into HK-2 cells transfected with and without CCN1 siRNA to investigate the mechanism of protective effect of Scu on LPS-induced HK-2 cells injury. RESULTS: (1) The results of in vivo experiment: the renal function of SA-AKI mice induced by LPS was significantly decreased, and had kidney histological damage and severely damaged renal tubules. Scu could alleviate renal function and histological damage in a dose-dependent manner. Western blotting results showed Scu could reduce the protein expression of NF-κB signaling pathway related molecules and CCN1 in the renal tissue, and had a significant alleviating effect on apoptosis, indicating that CCN1 was involved in NF-κB signaling pathway activation and apoptosis. (2) The results of in vitro experiment: in HK-2 cells not treated with LPS, CCN1 overexpression had no effect on apoptosis related protein and pro-inflammatory factors of NF-κB signaling pathway. In HK-2 cells treated with LPS, overexpression of CCN1 significantly inhibited the mRNA expressions of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), with significant differences as compared with cells stimulated only by LPS [IL-1ß mRNA (2-ΔΔCT): 3.20±0.57 vs. 4.88±0.69, TNF-α mRNA (2-ΔΔCT): 2.99±0.44 vs. 5.00±0.81, MCP-1 mRNA (2-ΔΔCT): 2.81±0.50 vs. 5.41±0.75, all P < 0.05], and the apoptosis-related protein was significantly down-regulated. However, when siRNA was used to inhibit the expression of CCN1, the mRNA expressions of pro-inflammatory factors were significantly increased as compared with cells stimulated only by LPS [IL-1ß mRNA (2-ΔΔCT): 6.01±1.13 vs. 4.88±0.69, TNF-α mRNA (2-ΔΔCT): 5.15±0.86 vs. 5.00±0.81, all P < 0.05], and apoptosis-related protein was significantly up-regulated. In the LPS-induced HK-2 cells, the mRNA expressions of pro-inflammatory factors were significantly down-regulated after Scu treatment as compared with cells stimulated only by LPS [IL-1ß mRNA(2-ΔΔCT): 2.55±0.50 vs. 6.15±1.04, TNF-α mRNA (2-ΔΔCT): 2.58±0.40 vs. 3.95±0.52, MCP-1 mRNA (2-ΔΔCT): 2.64±0.44 vs. 6.21±0.96, all P < 0.05], and apoptosis-related protein was also significantly reduced. When the expression of CCN1 was inhibited by siRNA, the protective effect of Scu on cells was weakened, which showed that the mRNA expressions of pro-inflammatory factors in cells was significantly up-regulated compared with the cells without inhibition of CCN1 expression [IL-1ß mRNA (2-ΔΔCT): 5.34±0.76 vs. 2.55±0.50, TNF-α mRNA (2-ΔΔCT): 3.66±0.54 vs. 2.58±0.40, MCP-1 mRNA (2-ΔΔCT): 5.15±0.79 vs. 2.64±0.44, all P < 0.05], and the expression of apoptosis related protein was also significantly up-regulated. CONCLUSIONS: Scu could protect the renal function in SA-AKI mice, and the protective effect is associated with NF-κB signaling pathway and CCN1. Thus, Scu could alleviate LPS-induced kidney injury by regulating the NF-κB signaling pathway.

Balancing Damage via Non-Photochemical Quenching, Phenolic Compounds and Photorespiration in Ulva prolifera Induced by Low-Dose and Short-Term UV-B Radiation.

The Yellow Sea green tide (YSGT) is the world's largest transregional macroalgal blooms, and the causative species Ulva prolifera (U. prolifera) suffers from ultraviolet-b radiation (UVBR) during the floating migration process. Previous study confirmed that U. prolifera displayed a wide variety of physiological responses characterized as acclimation to UVBR, while the response mechanisms against low-dose and short-term radiation (LDSTR) are not clear. A study with photosynthetically active radiation (PAR) and UVBR was designed: normal light (NL: 72 µmol photons m-2 s-1), NL+0.3 (UVBR: 0.3 W·m-2), and NL+1.6 (UVBR: 1.6 W·m-2). The results showed that high-dose UVBR inhibited photosynthesis in thalli, especially under long-term exposure, while a variety of physiological responses were observed under LDSTR. The inhibition of photosynthesis appeared to be ameliorated by the algae under LDSTR. Further analysis showed that U. prolifera achieved balancing damage by means of non-photochemical quenching (NPQ), accumulation of phenolic compounds coupled with the ASA-GSH cycle involved in the antioxidant process and enhanced photorespiratory metabolism under LDSTR. This study provides new insights into the balancing damage mechanisms of U. prolifera under LDSTR, enabling the thalli to adapt to the light conditions during the long duration and distance involved in floating migration.

Classification of histopathological images of breast cancer using an improved convolutional neural network model.

The accurately automatic classification of medical pathological images has always been an important problem in the field of deep learning. However, the traditional manual extraction of features and image classification usually requires in-depth knowledge and more professional researchers to extract and calculate high-quality image features. This kind of operation generally takes a lot of time and the classification effect is not ideal. In order to solve these problems, this study proposes and tests an improved network model DenseNet-201-MSD to accomplish the task of classification of medical pathological images of breast cancer. First, the image is preprocessed, and the traditional pooling layer is replaced by multiple scaling decomposition to prevent overfitting due to the large dimension of the image data set. Second, the BN algorithm is added before the activation function Softmax and Adam is used in the optimizer to optimize performance of the network model and improve image recognition accuracy of the network model. By verifying the performance of the model using the BreakHis dataset, the new deep learning model yields image classification accuracy of 99.4%, 98.8%, 98.2%and 99.4%when applying to four different magnifications of pathological images, respectively. The study results demonstrate that this new classification method and deep learning model can effectively improve accuracy of pathological image classification, which indicates its potential value in future clinical application.

Red Phosphorus Decorated TiO2 Nanorod Mediated Photodynamic and Photothermal Therapy for Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a serious and tenacious disease. Photodynamic therapy (PDT) and photothermal therapy (PTT) are effective means of cancer treatment. However, PDT combined with PTT has been rarely reported in ccRCC treatment. In the present study, by developing the core-shell structured TiO2 @red phosphorus nanorods (TiO2 @RP NRs) as a photosensitizer, the feasibility and effectiveness of synchronous PDT and PTT treatments for ccRCC are demonstrated. The core-shell structured TiO2 @RP NRs are synthesized to drive the PDT and PTT for ccRCC, in which the RP shell is the sensitizer even in the near-infrared (NIR) region. The optimized TiO2 @RP NRs can respond to NIR and produce local heat under irradiation. The NRs are estimated in ccRCC treatments via cell counting kit-8 assay, propidium iodide staining, qRT-PCR, and reactive oxygen species (ROS) probes in vitro, while terminal deoxynucleotidyl transferase dUTP nick-end labeling is conducted in vivo. After NIR irradiation, TiO2 @RP NRs can efficiently kill ccRCC cells by producing local heat and ROS and cause low injury to normal kidney cells. Furthermore, treatment with TiO2 @RP NRs and NIR can kill significant numbers of deep-tissue ccRCC cells in vivo. This work highlights a promising photo-driven therapy for kidney cancer.

Serum response factor, a novel early diagnostic biomarker of acute kidney injury.

OBJECTIVE: Studies have shown that serum response factor (SRF) is increased in chronic kidney injury, such as diabetic nephropathy, hyperuricemic nephropathy and renal cell carcinoma. The objective is to explore the early diagnostic value of SRF in acute kidney injury (AKI). METHODS: AKI-related microarray data were analyzed, and the expression and location of SRF were investigated in the early phase of AKI. RESULTS: Bioinformatics results demonstrated that SRF was dramatically elevated 2-4 h after ischemia/reperfusion (I/R) in mouse renal tissue. In I/R rats, SRF was mostly expressed and located in renal tubular epithelial cells (TECs). SRF started to increase at 1 h, peaked at 3-9 h and started to decrease at 12 h after I/R. The areas under the ROC curve of renal SRF mRNA, renal SRF protein, urinary SRF, serum SRF and serum creatinine (Scr) were 87.9%, 83.0%, 81.3%, 78.8%, 68.8%, respectively. CONCLUSION: SRF is remarkably upregulated in early (before 24 h) AKI and can replace Scr as a potential new early diagnostic biomarker of AKI.

Scutellarin Ameliorates Renal Injury via Increasing CCN1 Expression and Suppressing NLRP3 Inflammasome Activation in Hyperuricemic Mice.

Considerable evidences have indicated that elevated uric acid (UA) was involved in renal tubular injury leading to hyperuricemic nephropathy (HN). Scutellarin is a biologically active flavonoid derived from the Chinese traditional herb Erigeron breviscapus Hand-Mazz, which has been widely used in the treatment of cardiovascular and cerebrovascular diseases. In the present study, we analyzed the effect of scutellarin on HN, by using C57BL/6 mice and human renal tubular epithelial cell line HK-2 which was subjected to adenine/potassium oxonate and UA to mimic a HN injury. The HN mice showed a significant decrease in renal function with the increased SCr and blood urea nitrogen (BUN) (p < 0.05). Hematoxylin-eosin staining results showed a histological injury in HN mice kidney tissues with severe tubular damage. Scutellarin dose dependently alleviated the renal injury of the HN model (p < 0.05), and a dose of 20 mg/kg/day remarkably reduced the Scr level (26.10 ± 3.23 µmol/ml vs. 48.39 ± 7.51 µmol/ml, p < 0.05) and BUN (151.12 ± 30.24 mmol/L vs. 210.43 ± 45.67 mmol/L, p < 0.05) compared with the HN model group. Similarly, scutellarin decreased NGAL, Kim-1, cystatin C, and IL-18 protein expression levels in HN mouse (p < 0.05). Overexpressed CCN1 could not induce NLRP3 inflammasome activation, with no change of mRNA and protein expression levels of NLRP3, ASC, and pro-caspase-1 compared with the control HK-2. However, HK-2 showed a significant NLRP3 inflammasome activation and apoptosis. Importantly, knockdown of CCN1 not only aggravated NLRP3 inflammasome activation and apoptosis but also abrogated the protective effect of scutellarin in UA-induced HK-2 injury. Thus, scutellarin might alleviate HN progression via a mechanism involved in CCN1 regulation on NLRP3 inflammasome activation.

[Risk factors of acute kidney injury in hospitalized patients with infective endocarditis and their predictive values].

OBJECTIVE: To analyze the risk factors of acute kidney injury (AKI) in hospitalized patients with infective endocarditis (IE), construct prediction model, and discuss its predictive value. METHODS: The clinical data of 402 adult inpatients diagnosed with IE admitted to the Affiliated Hospital of Qingdao University from January 2010 to January 2020 were retrospectively analyzed. The patients were divided into the AKI group and the non-AKI group. The clinical data, such as gender, age, presence of diabetes, basic estimated glomerular filtration rate (eGFR), laboratory indexes at admission, involvement of valves, presence of sepsis, medication during hospitalization, surgery and outcome of the two groups were compared. Multivariate Logistic regression analysis was used to screen the risk factors of AKI in IE inpatients. A predictive model was constructed, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of the model. RESULTS: A total of 290 patients with IE were enrolled, including 198 non-AKI patients and 92 AKI patients. The incidence of AKI was 31.7%. Among the 92 AKI patients, 46 patients were at AKI stage 1 (50.0%), while 46 patients were at AKI stage 2 and stage 3 (50.0%). Compared with the non-AKI group, patients in the AKI group were older [years old: 64 (55, 71) vs. 55 (46, 63)], and had lower basic eGFR (mL×min-1×1.73 m-2: 64.6±13.6 vs. 82.9±19.5), higher proportion of diabetic and incidence of sepsis (16.3% vs. 8.6%, 38.0% vs. 13.1%), more frequent use of angiotensin converting enzyme inhibitors/angiotensin II receptor antagonists (ACEI/ARB), diuretics and non-steroidal anti-inflammatory drugs (NSAIDs; 25.0% vs. 15.2%, 82.6% vs. 63.1%, 58.7% vs. 24.2%), more abnormal urine test results (hematuria or proteinuria, 35.9% vs. 22.7%), higher pathogen culture negative rate (73.9% vs. 51.5%), lower Gram positive (G+) cocci infection rate and surgery rate (22.8% vs. 40.4%, 60.9% vs. 81.8 %), with significant differences (all P < 0.05). There were no significant differences in the gender, number and location of involved valves, and laboratory indexes at admission between the two groups. Compared with the non-AKI group, the inpatient mortality rate of the AKI group was higher (30.4% vs. 8.6%, P < 0.01), and the inpatient mortality rate of patients with AKI stage 2 and stage 3 was significantly higher than that of patients with AKI stage 1 (43.5% vs. 17.4%, P < 0.01). In multivariate Logistic regression analysis, the lower basic eGFR [hazard ratio (HR) = 0.136, 95% confidence interval (95%CI) was 0.066-0.280], sepsis (HR = 6.100, 95%CI was 2.394-15.543), demand for NSAIDs (HR = 2.990, 95%CI was 1.184-7.546) and radiocontrast agent (HR = 3.153, 95%CI was 1.207-8.238) were independent risk factors for AKI in hospitalized patients with IE (all P < 0.05). A prediction model was constructed based on the above risk factors, and ROC curve analysis showed that the area under the ROC curve (AUC) of prediction model for AKI was 0.888 (95%CI was 0.833-0.943, P < 0.01) with sensitivity of 86.4% and specificity of 80.9%. CONCLUSIONS: In the IE-susceptible population, low basic eGFR, sepsis, the need for NSAIDs and contrast agent are independent risk factors to AKI. The predictive model constructed by the above risk factors has certain predictive value for the occurrence of AKI in the IE inpatients.

A visual risk assessment tool for acute kidney injury after intracranial aneurysm clipping surgery.

OBJECTIVE: The aim of the study was to establish a predictive postoperative nomogram for acute kidney injury (AKI) after intracranial aneurysm clipping surgery, in order to early identify patients with high postoperative AKI risk. METHODS: This is a retrospective study, which included patients who underwent intracranial aneurysm clipping surgery. Multivariate logistic regression was employed to select confound factors that associated with AKI, then incorporated into the nomogram. The predictive accuracy of the model was assessed by concordance index (C-Index). RESULTS: A total of 365 patients after intracranial aneurysm clipping surgery were enrolled in the study eventually, of which 68 (18.63%) suffered postoperative AKI, and the incidence of stage 1, stage 2 and stage 3 were 92.65% (63/68), 5.88% (4/68), and 1.47% (1/68), respectively. Univariate logistic regression revealed that high density lipoprotein (HDL), prothrombin time (PT), estimated glomerular filtration rate (eGFR), size of aneurysm ≥10 mm, and aneurysm ruptured before surgery were associated with AKI after surgery, while multivariate logistic regression showed same results as the size of aneurysm ≥10 mm and aneurysm ruptured were independent AKI risk factors. In addition, the nomogram demonstrated a good accuracy in estimating intracranial aneurysm clipping associated AKI, as a C-Index and a bootstrap-corrected one of 0.772 and 0.737, respectively. Moreover, calibration plots showed consistency with the actual presence of AKI. CONCLUSION: The novel nomogram model can serve as a promising predictive tool to improve the identification of AKI among those who underwent intracranial aneurysm clipping surgery.

Esophageal Histological Precursor Lesions and Subsequent 8.5-Year Cancer Risk in a Population-Based Prospective Study in China.

INTRODUCTION: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines. METHODS: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models. RESULTS: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women. DISCUSSION: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.

Malnutrition screening and acute kidney injury in hospitalised patients: a retrospective study over a 5-year period from China.

Malnutrition and acute kidney injury (AKI) are common complications in hospitalised patients, and both increase mortality; however, the relationship between them is unknown. This is a retrospective propensity score matching study enrolling 46 549 inpatients, aimed to investigate the association between Nutritional Risk Screening 2002 (NRS-2002) and AKI and to assess the ability of NRS-2002 and AKI in predicting prognosis. In total, 37 190 (80 %) and 9359 (20 %) patients had NRS-2002 scores <3 and ≥3, respectively. Patients with NRS-2002 scores ≥3 had longer lengths of stay (12·6 (sd 7·8) v. 10·4 (sd 6·2) d, P < 0·05), higher mortality rates (9·6 v. 2·5 %, P < 0·05) and higher incidence of AKI (28 v. 16 %, P < 0·05) than patients with normal nutritional status. The NRS-2002 showed a strong association with AKI, that is, the risk of AKI changed in parallel with the score of the NRS-2002. In short- and long-term survival, patients with a lower NRS-2002 score or who did not have AKI achieved a significantly lower risk of mortality than those with a high NRS-2002 score or AKI. Univariate Cox regression analyses indicated that both the NRS-2002 and AKI were strongly related to long-term survival (AUC 0·79 and 0·71) and that the combination of the two showed better accuracy (AUC 0·80) than the individual variables. In conclusion, malnutrition can increase the risk of AKI and both AKI and malnutrition can worsen the prognosis that the undernourished patients who develop AKI yield far worse prognosis than patients with normal nutritional status.

Risk factors of cardiac surgery-associated acute kidney injury: development and validation of a perioperative predictive nomogram.

OBJECTIVE: Cardiac surgery-associated acute kidney injury (CSA-AKI), one of the most severe complications in patients with cardiac surgery, is associated with considerable morbidity, mortality and high costs thus placing a heavy burden to society. Therefore, we aimed to build a predictive model based on preoperative features in order to early recognize and intervene for patients with high risk of CSA-AKI. METHODS: In this retrospective cohort study, baseline perioperative hospitalization information of patients who underwent cardiac surgery from October 2012 to October 2017 were screened. After multivariate logistic regression, identified independent predictive factors associated with CSA-AKI were incorporated into the nomogram and the discriminative ability and predictive accuracy of the model was assessed by concordance index (C-Index). Additionally, internal validation was performed by using bootstrapping technology with 1000 resamples to reduce the over-fit bias. RESULTS: In all 4395 patients with cardiac surgery October 2012-October 2017, no patients were excluded for the continuous renal replacement therapy (CRRT) before surgery while 2495 patients were excluded due to only one or less than one Scr assay post-surgery. In the end, a total of 1900 patients were enrolled in the study, of which 698 patients (74.89%) developed AKI stage 1, 158 (16.96%) AKI stage 2 and 76 (8.15%) AKI stage 3. After multivariate logistic regression, age, perioperative estimated glomerular filtration rate (eGFR), lactate dehydrogenase (LDH), prothrombin time (PT), with a history of surgery, transfusion, cardiac arrhythmia, coronary heart disease (CHD), or chronic kidney disease (CKD), using calcium channel blocker (CCB), proton pump inhibitors (PPI), non-steroidal anti-inflammatory drugs (NSAID), antibiotic or statin before surgery were predictive factors of CSA-AKI. In addition, the nomogram demonstrated a good accuracy in estimating CSA-AKI, with an C-Index and a bootstrap-corrected one of 0.796 (SD = 0.018, 95% CI 0.795-0.797) and 0.789 (SD = 0.015, 95% CI 0.788-0.790), respectively. Moreover, calibration plots showed an optimal consistency with the actual presence of CSA-AKI. CONCLUSION: The novel predictive nomogram achieved a good preoperative prediction of CSA-AKI within the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Though the model, the risk of an individual patient with "subclinical AKI" undergoing cardiac surgery could be determined earlier and such application was helpful for timely intervention in order to improve patient's prognosis.

Upregulation of MicroRNA-21 promotes tumorigenesis of prostate cancer cells by targeting KLF5.

Prostate cancer (PCa) is the second frequently newly diagnosed cancer in men. Androgen deprivation therapy has been widely used to inhibit PCa growth but eventually fails in many patients. Androgen receptor and its downstream molecules like microRNAs could be promising therapeutic targets. We aimed to investigate the involvement of miR-21 in PCa tumorigenesis. We found that miR-21 was an unfavorable factor and correlated positively with tumor grade in PCa patients from TCGA database. MiR-21 was more highly expressed in androgen-independent PCa cells than in androgen-dependent PCa cells. Overexpression of miR-21 promoted androgen-dependent and -independent PCa cell proliferation, migration, invasion, and resistance to apoptosis. Furthermore, increased miR-21 expression promoted mouse xenograft growth. We identified nine genes differentially expressed in PCa tumors and normal tissue which could be potential targets of miR-21 by bioinformatic analyses. We demonstrate that miR-21 directly targeted KLF5 and inhibited KLF5 mRNA and protein levels in PCa. STRING and functional enrichment analysis results suggest that GSK3B might be regulated by KLF5. Our findings demonstrate that miR-21 promotes the tumorigenesis of PCa cells by directly targeting KLF5. These biological effects are mediated through upregulation of GSK3B and activation of the AKT signaling pathway.

[Reviews on natural naphthoquinones and their bioactivities].

The naphthaquinones are widely distributed in plants. They are usually in higher plants, but a few of them were also found in microorganisms. There is a lot of research showing that they had multiple pharmaco-activities such as cytotoxic, antioxidant, anti-inflammatory and antibacterial activities, etc. In recent years, they have attracted extensive attention at home and abroad especially in terms of the anti-tumor activity. For further research, 69 new natural naphthoquinones reported in the last five years (2013-2017) were reviewed. They were divided into five major types: simple 1,4-naphthoquinones, furan and pyran naphthoquinones, 1,2-naphthoquinones, naphthohydroquinones and naphthoquinone polymers, which showed cytotoxic, antioxidative, anti-inflammatory and antibacterial biological activities, et al. The research of these compounds in the future was also proposed.

A novel RNA sequencing-based miRNA signature predicts with recurrence and outcome of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the second leading cause of cancer-related deaths worldwide. Given that the rate of HCC recurrence 5 years after liver resection is as high as 70%, patient with HCC typically has a poor outcome. A biomarker or set of biomarkers that could predict disease recurrence would have a substantial clinical impact, allowing earlier detection of recurrence and more effective treatment. With the aim of identifying a new microRNA (miRNA) signature associated with HCC recurrence, we analyzed data on 306 patients with HCC for whom both miRNA expression profiles and complete clinical information were available from The Cancer Genome Atlas database. Through this analysis, we identified a six-miRNA signature that could effectively predict patients' recurrence risk; the high-risk and low-risk groups had significantly different recurrence-free survival rates. Time-dependent receiver operating characteristic analysis indicated that this signature had a good predictive performance. Multivariable Cox regression and stratified analyses demonstrated that the six-miRNA signature was independent of other clinical features. Functional enrichment analysis of the gene targets of the six prognostic miRNA indicated enrichment mainly in cancer-related pathways and important cell biological processes. Our results support use of this six-miRNA signature as an independent factor for predicting recurrence and outcome of patients with HCC.