[Development and validation of a nomogram for predicting 3-month mortality risk in patients with sepsis-associated acute kidney injury].

OBJECTIVE: To develop and evaluate a nomogram prediction model for the 3-month mortality risk of patients with sepsis-associated acute kidney injury (S-AKI). METHODS: Based on the American Medical Information Mart for Intensive Care- IV (MIMIC- IV), clinical data of S-AKI patients from 2008 to 2021 were collected. Initially, 58 relevant predictive factors were included, with all-cause mortality within 3 months as the outcome event. The data were divided into training and testing sets at a 7 : 3 ratio. In the training set, univariate Logistic regression analysis was used for preliminary variable screening. Multicollinearity analysis, Lasso regression, and random forest algorithm were employed for variable selection, combined with the clinical application value of variables, to establish a multivariable Logistic regression model, visualized using a nomogram. In the testing set, the predictive value of the model was evaluated through internal validation. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the curve (AUC) was calculated to evaluate the discrimination of nomogram model and Oxford acute severity of illness score (OASIS), sequential organ failure assessment (SOFA), and systemic inflammatory response syndrome score (SIRS). The calibration curve was used to evaluate the calibration, and decision curve analysis (DCA) was performed to assess the net benefit at different probability thresholds. RESULTS: Based on the survival status at 3 months after diagnosis, patients were divided into 7 768 (68.54%) survivors and 3 566 (31.46%) death. In the training set, after multiple screenings, 7 variables were finally included in the nomogram model: Logistic organ dysfunction system (LODS), Charlson comorbidity index, urine output, international normalized ratio (INR), respiratory support mode, blood urea nitrogen, and age. Internal validation in the testing set showed that the AUC of nomogram model was 0.81 [95% confidence interval (95%CI) was 0.80-0.82], higher than the OASIS score's 0.70 (95%CI was 0.69-0.71) and significantly higher than the SOFA score's 0.57 (95%CI was 0.56-0.58) and SIRS score's 0.56 (95%CI was 0.55-0.57), indicating good discrimination. The calibration curve demonstrated that the nomogram model's calibration was better than the OASIS, SOFA, and SIRS scores. The DCA curve suggested that the nomogram model's clinical net benefit was better than the OASIS, SOFA, and SIRS scores at different probability thresholds. CONCLUSIONS: A nomogram prediction model for the 3-month mortality risk of S-AKI patients, based on clinical big data from MIMIC- IV and including seven variables, demonstrates good discriminative ability and calibration, providing an effective new tool for assessing the prognosis of S-AKI patients.

Performance of next-generation sequencing for diagnosis of blood infections by Klebsiella pneumoniae.

Objective: Klebsiella pneumoniae (Kp) bloodstream infections (BSI) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for Kp BSI. Methods: We retrospectively analyzed 72 patients suspected with bloodstream infection and mNGS Kp positive in peripheral blood, who were hospitalized in our hospital from January 2022 to January 2023. Clinical data and laboratory parameters were collected. All patients had blood drawn and other samples for blood mNGS, blood cultures (BC) and other cultures (OC). The accuracy of mNGS results was analyzed according to infection site, clinical indicators, therapeutic effect and routine culture results. The detection of pathogenic microorganisms by blood mNGS and routine culture was compared. Results: Among 72 infection patients, 29 cases (40.28%) were BC positive, 43 cases (59.72%) were other culture (OC) positive, 16 cases (22.22%) were both BC and OC positive, 56 cases were positive for both mNGS and routine culture. Among the 56 double-positive cases, mNGS and conventional cultures were completely consistent in 27 cases, partially consistent in 15 cases, and completely inconsistent in 14 cases. Using the clinical diagnosis as the reference standard, There were 51 cases consistent with the results of mNGS with Kp BSI, the clinical consistency was 70.83% (51/72). The coincidence rate of mNGS and clinical diagnosis was higher than that of BC (54.17%, 39/72), indicating a statistically significant difference between the two methods (P<0.01). Conclusions: Current evidence indicates that mNGS exhibits excellent accuracy for the diagnosis of Kp BSI. Although it cannot replace blood culture detection technology, it can be used as a supplement to provide stronger diagnostic capabilities for BSI and optimize treatment.

MiR-590-3p Promotes the Phenotypic Switching of Vascular Smooth Muscle Cells by Targeting Lysyl Oxidase.

ABSTRACT: We investigated the clinical characteristics of patients with acute aortic dissection (AAD) and miR-590-3p levels in serum, tissue, and vascular smooth muscle cells. The effect of miR-590-3p on the vascular smooth muscle cell phenotype was assessed, and the regulation of lysyl oxidase by miR-5903p was determined. C57BL/6 mice were used to investigate the incidence of AAD and effects of miR-5903p on AAD. The miR-590-3p levels were measured in the aortae of mice, and hematoxylin and eosin staining and Masson staining were performed to identify the morphological features of the aorta. Comparative analysis revealed significant differences in clinical characteristics between patients with AAD and healthy control subjects, with most patients with AAD exhibiting concomitant hypertension and nearly 50% having atherosclerosis. Lysyl oxidase was a direct target of miR-590-3p. Lysyl oxidase overexpression inhibited switching of the vascular smooth muscle cell phenotype from contractile to synthetic, but miR-590-3p overexpression significantly reversed this change. In the mouse model, miR-590-3p upregulation increased the incidence of AAD to 93.3%, and its incidence decreased to 13.3% after miR-590-3p inhibition. Hematoxylin and eosin and Masson staining revealed that the miR-590-3p agomiR group had a greater loss of the contractile phenotype in the dissected aortic wall and an increased number of muscle fibers in the aortic wall, which contributed to thickening of the aortic wall and the formation of a false lumen in aortic dissection. miR-590-3p might be pivotal in the pathogenesis of AAD. Thus, targeting miR-590-3p or its downstream pathways could represent a therapeutic approach for AAD.

Construction of a new clinical staging system for colorectal cancer based on the lymph node ratio: A validation study.

Aim: This study aims to construct a new staging system for colorectal cancer (CRC) based on the lymph node ratio (LNR) as a supplement to the American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system for predicting the prognosis of CRC patients with <12 lymph nodes. Methods: The data of 26,695 CRC patients with <12 lymph nodes were extracted from the Surveillance, Epidemiology, and End Results (SEER) database as a training set. A total of 635 CRC patients were also enrolled from Northern Jiangsu People's Hospital affiliated with Yangzhou University as an independent validation set. Classification and regression tree analysis was used to obtain the LNR cutoff value. Survival curves were estimated using the Kaplan-Meier method, and the log-rank test was used for comparisons of differences among the survival curves. The monotonic decreasing trend of the overall survival curve in the staging system was expressed by the linear correlation degree R. Results: The 5-year survival rates of patients in the training set based on the AJCC staging system from stage I to stage IV were 75.6% (95%CI: 74.4-76.8), 59.8% (95%CI: 58.6-61.0), 42.1% (95%CI: 34.5-49.7), 33.2% (95%CI: 24.6-41.8), 72.0% (95%CI: 69.1-74.9), 48.8% (95%CI: 47.4-50.2), 26.5% (95%CI: 23.0-30.0), and 11.3% (95%CI: 10.3-12.3). The 5-year survival rates of patients in the training set from stage I to stage IIIC were 80.4%, 72.9%, 59.8%, 48.4%, 32.5%, and 15.0%, according to the TNM + LNR (TNRM) staging system. According to the AJCC staging system, the 5-year survival rates of patients in the validation set from stage I to stage IIIC were 91.3%, 90.8%, 72.6%, 61.3%, 72.4%, 58.1%, and 32.8%. Based on the TNRM staging system, the 5-year survival rates of patients in the validation set from stage I to stage IIIC were 99.2%, 90.5%, 81.4%, 78.6%, 60.2%, and 35.8%. Conclusion: The TNRM staging system successfully eliminated "survival paradox" in the AJCC staging system, which might be superior to the AJCC staging system.

Microstructural Evolution and Tensile Properties of Al0.3CoCrFeNi High-Entropy Alloy Associated with B2 Precipitates.

The room-temperature strength of Al0.3CoCrFeNi high-entropy alloys (HEAs) is relatively low owing to its intrinsic fcc structure. In the present study, the as-cast HEAs were subjected to cold rolling and subsequent annealing treatment (800, 900, and 1000 °C) to adjust the microstructures and tensile properties. This treatment process resulted in the partial recrystallization, full recrystallization, and grain coarsening with increasing the annealing temperature. It was found that the large and spherical B2 precipitates were generated in the recrystallized grain boundaries of three annealing states, while the small and elongated B2 precipitates were aligned along the deformation twins in the non-recrystallized region of the 800 °C-annealing state. The former B2 precipitates assisted in refining the recrystallized grains to quasi ultra-fine grain and fine grain regimes (with the grain sizes of ~0.9, ~2.2, and ~7.2 µm). The tensile results indicated that the decreased annealing temperature induced the gradual strengthening of this alloy but also maintained the ductility at the high levels. The yield strength and ultimate tensile strength in 800 °C-annealed specimen were raised as high as ~870 and ~1060 MPa and the ductility was maintained at ~26%. The strengthening behavior derived from the heterogeneous microstructures consisting of quasi ultra-fine recrystallized grains, non-recrystallized grains, deformation twins, dislocations, and B2 precipitates. Current findings offer the guidance for designing the HEAs with good strength and ductility.

Up-regulation of Nrf2/P62/Keap1 involves in the anti-fibrotic effect of combination of monoammonium glycyrrhizinate and cysteine hydrochloride induced by CCl4.

Combination of monoammonium glycyrrhizinate and cysteine hydrochloride (MG-CH) has been used in the treatment of chronic liver disease for decades, however, its mechanism is still unclear. Our previous studies showed that MG-CH confers the optimal therapeutic effect at the ratio of 2:1 to against acute liver damage. In this study, it was used to investigate the anti-fibrotic effect induced by CCl4. The results showed that injection of MG-CH produced anti-fibrotic effect ranged from 30 mg/kg to 60 mg/kg, evidenced by decreased the collagens deposition and inhibited the production of hydroxyproline. Mechanism study found that Nrf2/ARE signaling pathway was activated by MG-CH, whereas loss of hepatocytic Nrf2 abolished its anti-fibrotic effect significantly. Furthermore, it was demonstrated that MG-CH is a non-canonical NRF2 inducer, which promoted the autophagy activity and release the Nrf2 from keap 1 by promoting the phosphorylation of p62 at Ser351. Knockdown of p62 abolished the enhancement of nuclear accumulation of Nrf2 by MG-CH. All of these results suggested that up-regulation of Nrf2/P62/Keap1 involves in the anti-fibrotic effect of MG-CH, which provide a rational explanation for the usage of MG-CH in the treatment of fibrosis.

MiR-4787-5p Regulates Vascular Smooth Muscle Cell Apoptosis by Targeting PKD1 and Inhibiting the PI3K/Akt/FKHR Pathway.

ABSTRACT: Vascular smooth muscle cell (VSMC) dysfunction is the main cause of aortic dissection (AD). In this study, we focused on the role and mechanism of miR-4787-5p in regulating VSMC apoptosis. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of miR-4787-5p in aorta tissues of AD (n = 10) and normal aortic tissues of donors (n = 10). Cell apoptosis was tested by TUNEL assay and Annexin V FITC/PI staining flow cytometry. The expression of PC1 and the PI3K/Akt/FKHR signaling pathway associated proteins in VSMCs was measured by Western blot. We found that the miR-4787-5p was highly expressed in aorta tissues of AD compared with 10 healthy volunteers. Meanwhile, PI3K/Akt/FKHR signaling pathway was inactive in the aortic tissue of AD. The overexpression of miR-4787-5p significantly induced VSMC apoptosis, and miR-4787-5p knockdown showed the opposite results. In addition, polycystic kidney disease 1 gene, which encodes polycystin-1 (PC1), was found to be a direct target of miR-4787-5p in the VSMCs and this was validated using a luciferase reporter assay. Overexpression of PC1 by a lentivirus packaging PC1-overexpression plasmid (LV-PC1) plasmids markedly eliminated the promotion of miR-4787-5p overexpression on VSMC apoptosis. Finally, it was found that miR-4787-5p deactivated the PI3K/Akt/FKHR pathway, as demonstrated by the down-regulation of phosphorylated (p-)PI3K, p-Akt, and p-FKHR. In conclusion, these findings confirm an important role for the miR-4787-5p/polycystic kidney disease 1 axis in AD pathobiology.

The Effects of Sand Particles on the Synergy of Cavitation Erosion-Corrosion of MIG Welding Stainless Steel Coating in Saline Water.

Cavitation erosion (CE) is a common problem troubling many flow-handling equipment such as valves, orifice plate pipes, and propellers. The coating technique is a widely used strategy to resist CE. It is important to understand the CE-corrosion behavior of the coatings in the corrosive solution, especially in the sand-containing saline water. A newly designed MIG welding precipitated hardened martensitic stainless steel (PHMSS) coating was performed, and its silt-CE was investigated in a suspension composed of 3.5 wt.% sodium chloride and 3% silica sand using an ultrasonic vibrator processor. The microstructure of the coating was characterized by optical microscopy and scanning electron microscopy. The effects of the sand particles on the CE-corrosion were analyzed using mass loss measurement, potentiodynamic polarization curve, and surface morphology observation. The results showed that the PHMSS coating was mainly composed of the lath martensitic phase alone. Its mass loss rate was in ascending order in the solution of distilled water alone, sand-containing distilled water, saline water alone, and sand-containing saline water. Sand particles played more roles in the CE in the distilled water than in the saline water. The synergy of CE and corrosion was much less in the sand-free saline than in the sand-containing saline. The maximum component was the erosion enhancement due to the corrosion in the saline without sand particles but was the pure erosion component in the saline with sand particles. The mechanism of the sand particles' effect on the CE was also discussed.

Short-term outcomes from drug-coated balloon for coronary de novo lesions in large vessels.

BACKGROUND: A drug-coated balloon (DCB) has been designed as a new device for the treatment of coronary artery disease. The data regarding DCB-treated lesions in large coronary artery are limited. The purpose of our study was to explore the effectiveness and safety of DCB in large coronary artery. METHODS: We prospectively analyzed all patients treated with DCB in de novo lesions consistent with inclusion criteria between May 2015 and April 2017. The observed outcomes included target lesion revascularization (TLR), myocardial infarction, cardiac death and non-cardiac death, and major adverse cardiac events (MACE). RESULTS: There were 92 patients including 94 coronary de novo lesions treated in all. The most often utilized DCB diameters were 3.0 mm (41.5%) and 3.5 mm (39.4%). Two acute closures occurred in hospital. Six bailout drug-eluting stents were used in the percutaneous coronary interventions (6.4%). Quantitative coronary angiography measurement at follow-up showed late lumen loss was -0.02 ± 0.49 mm. The TLR rate and overall MACE rates were 4.3% and 4.3% during the follow-up period in the whole patient population, respectively. CONCLUSIONS: Our study showed that the "DCB only" strategy is safe and efficient in large vessel lesions of patients whose predilation achieved an acceptable result.

Clinical Evaluation of Continuous Renal Replacement Therapy in Combination with Ultrasound-Guided Percutaneous Transhepatic Gallbladder Drainage for Acute Severe Biliary Pancreatitis: a Retrospective Study.

BACKGROUND/AIMS: This study aimed to report the clinical efficacy of continuous renal replacement therapy (CRRT) in combination with ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD) (CRRT+PTGD) in the treatment of acute severe biliary pancreatitis (ASBP). METHODS: Between January 2010 and January 2016, 40 cases of patients with ASBP who received routine CRRT (CRRT group) and 40 of those who received CRRT+PTGD (CRRT+PTGD group) at the Affiliated Hospital of Qingdao University (Qingdao, China) were retrospectively reviewed. Clinical (including abdominal pain remission time, gastrointestinal decompression time, Intensive Care Unit (ICU) hospital stay, respirator treatment time, and mortality rate), laboratory (white blood cells [WBC], platelet [PLT], procalcitonin [PCT], C-reactive protein [CRP], total bilirubin [TBIL], alanine aminotransferase [ALT], albumin [ALB], and blood lactic acid [Lac]) parameters, various critical disease scores, and incidence of complications after the treatment were compared between the two groups. RESULTS: Compared with those in the routine CRRT group, patients in the CRRT+PTGD group exhibited significant remission of clinical symptoms (i.e. shorter abdominal pain remission time, gastrointestinal decompression time, respirator treatment time and ICU hospital stay) (all P<0.05), change of laboratory parameters (WBC, PLT, PCT, CRP, TBIL, ALT) (P<0.05), and improvement of various critical disease scores (P<0.05). Moreover, the variation of most of the above parameters after versus before the treatment was greater in the CRRT+PTGD group than in the CRRT group (all P<0.05). CONCLUSION: CRRT in combination with PTGD is more effective in the treatment of ASBP than CRRT alone.

Biological nanoparticles carrying the Hmda-7 gene are effective in inhibiting pancreatic cancer in vitro and in vivo.

OBJECTIVES: Pancreatic cancer is one of the most common malignancies of the digestive system, and remains a clinical challenge. This study aimed to assess the effects of bovine serum albumin (BSA) nanoparticles carrying the hMDA-7 gene (BSA-NP-hMDA-7) in the treatment of pancreatic cancer. METHODS: BSA-NP-hMDA-7 was generated by nanotechnology and gene recombination technology. A total of 5 BXPC-3 or PANC-1 pancreatic cancer cell groups were examined, including Control, BSA-NPs, Empty vector, hMDA-7 plasmid, and hMDA-7 BSA-NPs groups, respectively. Proliferation and apoptosis of cultured cells were assessed by the MTT method and flow-cytometry, respectively. In addition, pancreatic cancer models were established with both cell lines in nude mice, and the expression profiles of hMDA-7 and VEGF in cancer tissues were measured by Western blot and immunohistochemistry. RESULTS: BSA-NP-hMDA-7 nanoparticles were successfully generated, and significantly inhibited the proliferation of BXPC-3 and PANC-1 cells; in addition, apoptosis rates were higher in both cell lines after treatment with BSA-NP-hMDA-7 (P<0.05). Nude mouse xenograft studies indicated that treatment with BSA-NP-hMDA-7 nanoparticles resulted in decreased tumor size. Moreover, the hMDA-7 protein was found in tumor tissues after hMDA-7 gene transfection, while BSA-NP-hMDA-7 significantly suppressed VEGF expression in tumor tissues. Similar results were obtained for both BXPC-3 and PANC-1 xenograft models. CONCLUSION: BSA nanoparticles carrying the hMDA-7 gene effectively transfected BXPC-3 and PANC-1 pancreatic cancer cells, causing reduced cell proliferation and enhanced apoptosis in vitro. In mouse xenografts, BSA-NP-hMDA-7 treatment decreased tumor size and reduced VEGF expression. These findings indicated that BSA-NP-hMDA-7 might exert anticancer effects via VEGF suppression.

Assessment of mitochondrial DNA mutations in Chinese family with essential hypertension.

Mitochondrial DNA (MtDNA) mutations played an important role in the development of essential hypertension. Mitochondrial tRNA point mutations, caused the failure in tRNA metabolism, responsible for the pathogenesis of this complex disease. In this study, we evaluated the possible role of the 4329C >G mutation in the clinical expression of hypertension in a Chinese family. Analysis of the complete mtDNA sequence variants showed that other mutations may play synergic roles in the phenotypic manifestation of hypertension. In addition, other potential pitfalls were also discussed in this context.

Research on antioxidant activity of EOB-F and its function in the diagnosis of heart and cerebral vessels.

This paper introduces the research progress related to the antioxidant activity of bamboo leaf flavonoid (EOB-f) and its pharmacological activity of heart and cerebral vessels. The paper studied what role EOB-f played in the diagnosis of heart and cerebral vessels, based on the in vitro, in vivo and animal model as well as the pharmacological research experiment. 1) The in vitro and in vivo experiments indicated that EOB-f has the function of anti-reactive-oxide species, anti-aging and anti-fatigue; 2) The research of animal model indicated that EOB-f can significantly decrease the triglyceride (TG) content in serum, significantly increase high density lipoprotein cholesterol (HDL-C) content in serum, regulate blood lipids and reduce the risk of atherosclerosis; 3) The pharmacological study showed that EOB-f has the effect to resist the whole animal anoxia, can effectively dilate coronary vessels, increase coronary flow, increase myocardial contractility, obviously improve myocardial ischemia and diminish the myocardial infarction scope, inhibit the coagulation process and reduce platelet aggregation, and has certain protective effect on cerebral ischemia. EOB-f has the potential to develop as the natural drug and functional foods for prevention of cardiovascular and cerebrovascular diseases.

Preliminary study on the role of virtual touch tissue quantification combined with a urinary ß2-microglobulin test on the early diagnosis of gouty kidney damage.

The goal of the work described here was to evaluate the role of virtual touch tissue quantification (VTQ) combined with urinary ß2-microglobulin (ß2-MG) measurement in the early diagnosis of gouty kidney damage. Two hundred fifty-nine patients with gouty kidney damage and 200 healthy control subjects were tested. The shear wave velocity (SWV) of the renal parenchyma and sinus as determined with VTQ and the urinary ß2-MG level of the two groups were analyzed. Although there were no significant differences in age, body mass index, creatinine level and blood urea nitrogen between the two groups (all p's > 0.05), the aforementioned parameters were higher in the group with gouty kidney damage than in the control group. Urinary ß2-MG levels of the patients with kidney damage were significantly higher than those of the control subjects (t = 6.38, p < 0.01). The SWV of the renal parenchyma was higher than that of the sinus in both groups. Compared with controls, patients with kidney damage had significantly increased renal parenchyma and sinus SWVs (all p-values < 0.05). Urinary ß2-MG level was positively linearly correlated with the SWV of renal parenchyma in patients with kidney damage (r = 0.442, p < 0.0001). However, there was no correlation between urinary ß2-MG level and the SWV of the sinus in patients with kidney damage (r = 0). In the control group, there was no correlation between urinary ß2-MG level and the SWV of the renal parenchyma or sinus. The elasticity of the kidney as determined with VTQ, combined with the urinary ß2-MG level, may be helpful in the early diagnosis of gouty kidney damage.

Polarization modulation by tunable electromagnetic metamaterial reflector/absorber.

We propose a polarization modulation scheme of electromagnetic (EM) waves through reflection of a tunable metamaterial reflector/absorber. By constructing the metamaterial with resonant unit cells coupled by diodes, we demonstrate that the EM reflections for orthogonal polarized incident waves can be tuned independently by adjusting the bias voltages on the corresponding diodes. Owing to this feature, the reflected EM waves can be electrically controlled to a linear polarization with continuously tunable azimuth angle from 0° to 90° at the resonant frequency, or an elliptical polarization with tunable azimuth angle of the major axis when off the resonant frequency. The proposed property has been verified through both numerical simulations and experimental measurements at microwave band, which enables us to electrically modulate the polarization state of EM waves flexibly.