Stretchable Oxygen-Tolerant Sensor Based on a Single-Atom Fe-N4 Electrocatalyst for Observing the Role of Oxidative Stress in Hypertension.

Oxidative stress and related oxidative damage have a causal relation with the pathogenesis of hypertension. Therefore, it is crucial to determine the mechanism of oxidative stress in hypertension by applying mechanical forces on cells to simulate hypertension while monitoring the release of reactive oxygen species (ROS) from cells under an oxidative stress environment. However, cellular level research has rarely been explored because monitoring the ROS released by cells is still challenging owing to the interference of O2. In this study, an Fe single-atom-site catalyst anchored on N-doped carbon-based materials (Fe SASC/N-C) was synthesized, which exhibits excellent electrocatalytic activity for the reduction of hydrogen peroxide (H2O2) at a peak potential of +0.1 V and can effectively avoid the interference of O2. Furthermore, we constructed a flexible and stretchable electrochemical sensor based on the Fe SASC/N-C catalyst to study the release of cellular H2O2 under simulated hypoxic and hypertension conditions. Density functional theory calculations show that the highest transition state energy barrier from the oxygen reduction reaction (ORR), i.e., O2 to H2O, is 0.38 eV. In comparison, the H2O2 reduction reaction (HPRR) can be completed only by overcoming a lower energy barrier of 0.24 eV, endowing the HPRR to be more favorable on Fe SASC/N-C compared with the ORR. This study provided a reliable electrochemical platform for real-time investigation of H2O2-related underlying mechanisms of the hypertension process.

Test Pilot and Airline Pilot Differences in Facing Unexpected Events.

BACKGROUND: Unexpected events in flight might decrease the transparency of the flying process and weaken the pilot's perception of the current state, or even erode manipulating skills. However, during the flight test of a new or modified aircraft, to verify the boundaries of aircraft aerodynamic performance and handling stability, unexpected events may be encountered that need to be handled by the test pilot. Therefore, studying the differences between test pilots and airline pilots could help improve flight safety.METHODS: Two kinds of physiological parameters, eye blink rate and average fixation duration and task-related performance of test pilots and airline pilots, were analyzed in three abnormal scenarios. A total of 16 pilots participated. The study was carried out in an A320 flight simulator.RESULTS: The differences were significant for both test pilots and airline pilots in eye blink rate and average fixation duration. Furthermore, the reaction time of test pilots (Mean = 23.38 s) was significantly shorter than airline pilots (Mean = 42.63 s) in Unreliable Airspeed condition, and the pitch angle deviations between them were significant in both Wind Shear and Unreliable Airspeed condition.DISCUSSION: The uncertainty of environmental change could create more severe pressure and mental workload influence than actual system failure. For airline pilots, compared with test pilots, the importance of practicing manual flight should still be emphasized. Improving reactions to unexpected ambient conditions and unannounced fault status could also contribute to flight safety.Zheng Y, Lu Y, Jie Y, Zhao Z, Fu S. Test pilot and airline pilot differences in facing unexpected events. Aerosp Med Hum Perform. 2023; 94(1):18-24.

Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites.

Background: Lingguizhugan decoction is a traditional Chinese medicine prescription that has been used to improve non-alcoholic fatty liver disease and its progressive form, non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and underlying mechanisms of Lingguizhugan decoction remain unclear. Methods: Male Sprague-Dawley rats were fed a methionine- and choline-deficient (MCD) diet to induce NASH, and then given Lingguizhugan decoction orally for four weeks. NASH indexes were evaluated by histopathological analysis and biochemical parameters including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver triglycerides (TG), etc. Fecal samples of rats were subjected to profile the changes of gut microbiota and metabolites using 16S rRNA sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS). Bioinformatics was used to identify Lingguizhugan decoction reversed candidates, and Spearman's correlation analysis was performed to uncover the relationship among gut microbiota, fecal metabolites, and NASH indexes. Results: Four-week Lingguizhugan decoction treatment ameliorated MCD diet-induced NASH features, as evidenced by improved hepatic steatosis and inflammation, as well as decreased serum AST and ALT levels. Besides, Lingguizhugan decoction partially restored the changes in gut microbial community composition in NASH rats. Meanwhile, the relative abundance of 26 genera was significantly changed in NASH rats, and 11 genera (such as odoribacter, Ruminococcus_1, Ruminococcaceae_UCG-004, etc.) were identified as significantly reversed by Lingguizhugan decoction. Additionally, a total of 99 metabolites were significantly altered in NASH rats, and 57 metabolites (such as TDCA, Glutamic acid, Isocaproic acid, etc.) enriched in different pathways were reversed by Lingguizhugan decoction. Furthermore, Spearman's correlation analyses revealed that most of the 57 metabolites were significantly correlated with 11 genera and NASH indexes. Conclusion: Lingguizhugan decoction may exert protective effects on NASH partially by modulating gut microbiota and correlated metabolites.

Wilson disease in pregnancy: A case series.

RATIONALE: Hepatolenticular degeneration, also known as Wilson disease (WD), is an autosomal recessive inherited disease characterized by copper metabolism, which has complex clinical manifestations, and mainly including liver and nervous system lesions. Pregnancy combined with WD is extremely harmful to mothers and children, with high miscarriage rates, and premature birth rates and perinatal mortality. PATIENT CONCERNS: Here we introduced the basic information of 4 pregnant women with WD. The first pregnant woman had a 16-year history of WD, stopped taking penicillamine 1 year before pregnancy. The second woman had a 3-year history of WD and was taking penicillamine regularly, unintended pregnancy occurred 1 month after stopping the drug. The third woman had a history of WD for 5 years with penicillamine treatment. The 4th woman was found to have WD due to repeated missed miscarriage with abnormal liver function, after which penicillamine was regularly taken. Fortunately, she was pregnant again a year later. DIAGNOSES: The pregnant women in case 1 and case 2 were diagnosed with decompensated cirrhosis with coagulation dysfunction during pregnancy. The pregnant woman in case 3 was found to have liver cirrhosis by ultrasound, and the pregnant woman in case 4 did not have liver abnormalities during pregnancy. INTERVENTIONS: The pregnant woman in case 1 began to take copper-removing drugs and take a low-copper diet after finding the aggravation of the disease in the early stage of pregnancy, and had good compliance during pregnancy. The pregnant woman in case 2 had poor compliance during pregnancy and did not receive any treatment. The pregnant woman in case 3 refused to use copper elimination drugs during pregnancy, but took a low copper diet. The pregnant woman in case 4 had good compliance during pregnancy, and she was treated with drugs and low copper diet during the whole pregnancy. OUTCOMES: Three of the four pregnant women got a healthy baby but premature, and only the pregnant woman in case 2 had spontaneous abortion at 25 weeks. LESSONS: After comprehensive monitoring and multidisciplinary management of professional medical staff before and after pregnancy, WD pregnant women still have the opportunity to obtain a better pregnancy outcome and improve quality of life.

Electro-polarization of protein-like substances accelerates trans-cell-wall electron transfer in microbial extracellular respiration.

Electrical stimulation has been used to strengthen microbial extracellular electron transfer (EET), however, the deep-seated reasons remain unclear. Here we reported that Bacillus subtilis, a typical gram-positive bacterium capable of extracellular respiration, obtained a higher EET capacity after the electrical domestication. After the electrical domestication, the current generated by the EET of B. subtilis was 23.4-fold that of the control group without pre-domestication. Multiple lines of evidence in bacterial cells of B. subtilis, their cell walls, and a model tripeptide indicated that the polarization of amide groups after the electrical stimulation forwarded the H-bonds recombination and radical generation of protein-like substances to develop extracellular electron transfer via the proton-coupled pattern. The improved electrochemical properties of protein-like substances benefited the trans-cell-wall electron transfer and strengthen extracellular respiration. This study was the first exploration to promote microbial extracellular respiration by improving the electrochemical properties of protein-like substances in cell envelopes.

Hyperoside attenuates Cd-induced kidney injury via inhibiting NLRP3 inflammasome activation and ROS/MAPK/NF-κB signaling pathway in vivo and in vitro.

Cadmium accumulates in the kidney and causes inflammation. The NLRP3 inflammasome has been linked to the pathogenesis of inflammation. Hyperoside (HYP) possesses potent nephroprotective properties against of kidney injury. This study aimed to research the effects and related mechanism of HYP on Cd-induced kidney damage. Wide-type and NLRP3-/- mice were used to determine the role of NLRP3 inflammasome in Cd-induced renal dysfunction. Female C57BL/6 were treated with Cd (50 m,g/L) and HYP (25, 50 mg/kg) for 12 weeks. In vitro experiments, the human renal proximal-tubule epithelial cells (RPTEC/TERT1) were pretreated with HYP (50-200 µM) before exposure to Cd. NLRP3 deficiency attenuated Cd-induced NLRP3 activation, inflammation and kidney injury in mice. HYP treatment significantly alleviated Cd-induced kidney injury by decreasing indexes of kidney function, reducing pro-inflammatory cytokines release, decreasing ROS production and suppressing NLRP3 inflammasome activation. Moreover, treatment with siRNA targeting NLRP3 blocked the anti-inflammatory protective effect of HYP in Cd-treated cells. Additionally, HYP markedly inhibited Cd-induced MAPK/NF-κB pathway stimulation in vitro and in vivo. The findings indicated HYP conferred protection against Cd-induced kidney inflammation via suppression of NLRP3 inflammasome mediated by ROS/MAPK/NF-κB signaling. Our results thus support the notion of developing HYP as promising therapeutic candidate for Cd-induced kidney injury.

Emerging role of mitophagy in heart failure: from molecular mechanism to targeted therapy.

Heart failure is defined as a drop in heart's pump function, accounting for reduced blood output and venous stasis, and constitutes the end stage of various cardiovascular diseases. Although mild mitochondrial dysfunction may hinder cardiomyocyte metabolism and impair myocardial function, severe mitochondrial injury is accompanied by cardiomyocyte apoptosis, leading to irreversible damage of the heart. Selective autophagy of mitochondria, or mitophagy, serves to rapidly remove dysfunctional mitochondria and restore the health of the mitochondrial population within cells by allowing reutilization of degradative substrates such as amino acids, fatty acids, and nucleotides. Although mitophagy represents a protective program that prevents the accumulation of poorly structured or damaged mitochondria, excessive mitophagy leads to mitochondrial population decline, impaired oxidative phosphorylation, and decreased ATP production. In this review, we first discuss the molecular underpinnings of mitophagy and the roles of different mitophagy adaptors. Then, the multiple and complex influence of mitophagy on heart failure is summarized. Finally, novel pharmacological strategies targeting mitophagy to relieve heart failure are briefly summarized.

Molecularly self-fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke.

Thrombotic cerebro-cardiovascular diseases are the leading causes of disability and death worldwide. However, current drug therapeutics are compromised by narrow therapeutic windows, unsatisfactory thrombolysis effects, severe bleeding events, and high recurrence rates. In this study, we exploit a self-propelling nano-penetrator with high fuel loading and controllable motion features, which is molecularly co-assembled using a photothermal photosensitizer (DiR) and a photothermal-activable NO donor (BNN6). The precisely engineered nano-penetrator of the BNN6-DiR fuel pair shows distinct advantages in terms of NO productivity and autonomous motion under laser irradiation. In animal models of artery/vein thrombosis and acute ischemic stroke, the self-fueled nano-penetrator enables self-navigated thrombus-homing accumulation, self-propelled clot deep penetration, fluorescence image-guided photothermal/mechanical thrombolysis, and NO-mediated prevention of thrombosis recurrence and acute ischemic stroke salvage. As expected, the molecularly self-fueled nano-penetrator displayed favorable therapeutic outcomes without bleeding risk compared to the clinically available thrombolytic drug. This study offers a facile, safe, and effective nonpharmaceutical modality towards the clinical treatment of thrombosis and ischemic stroke.

Light Field-Enhanced Single-Site Cu Electrocatalyst for Nitrogen Fixation.

Direct electrocatalytic reduction of N2 to NH3 under mild conditions is attracting considerable interests but still remains enormous challenges in terms of respect of intrinsic catalytic activity and limited electrocatalytic efficiency. Herein, a photo-enhanced strategy is developed to improve the NRR activity on Cu single atoms catalysts. The atomically dispersed Cu single atoms supported TiO2 nanosheets (Cu SAs/TiO2 ) achieve a Faradaic Efficiency (12.88%) and NH3 yield rate (6.26 µg h-1 mgcat -1 ) at -0.05 V versus RHE under the light irradiation field, in which NH3 yield rate is fivefold higher than that under pure electrocatalytic nitrogen reduction reaction (NRR) process and is remarkably superior in comparison to most of the similar type electrocatalysts. The existence of external light field improves electron transfer ability between CuO and TiO, and thus optimizes the accumulation of surface charges on Cu sites, endowing more electrons involved in nitrogen fixation. This work reveals an atomic-scale mechanistic understanding of field effect-enhanced electrochemical performance of catalysts and it provides predictive guidelines for the rational design of photo-enhanced electrochemical N2 reduction catalysts.

Cobalt Single-Atom Nanozyme Co-Administration with Ascorbic Acid Enables Redox Imbalance for Tumor Catalytic Ablation.

The elevated antioxidant defense system in cancer cells can lead to resistance to treatments involving ROS. Breaking the redox balance of the cell system through a "open up the source and regulate the flow" strategy can inhibit the growth of cancer cells and thus design a cancer treatment strategy. Here, cobalt single atom-supported N-doped carbon nanozymes (Co SA-N/C) were synthesized via a simple sacrificial template method, which can mimic the properties of ascorbate oxidase and glutathione oxidase effectively. The synthesized Co SA-N/C can induce the generation of active oxygen by accelerating the oxidation of ascorbic acid (AA) and destroy the endogenous active oxygen scavenging system by consuming the main antioxidant, glutathione (GSH). In-depth in vitro and in vivo investigations indicate that compared with solo therapy, Co SA-N/C together with AA can significantly enhance the anti-tumor efficiency by simultaneously elevating oxidative stress and consuming the overexpressed glutathione (GSH) through the redox reaction catalyzed by Co SA-N/C. This work provides a promising route for developing nanozyme-guided and ascorbate-based antitumor agents.

Space-Charge Control of Magnetism in Ferromagnetic Metals: Coupling Giant Magnitude and Robust Endurance.

Ferromagnetic metals show great prospects in ultralow-power-consumption spintronic devices, due to their high Curie temperature and robust magnetization. However, there is still a lack of reliable solutions for giant and reversible voltage control of magnetism in ferromagnetic metal films. Here, a novel space-charge approach is proposed which allows for achieving a modulation of 30.3 emu/g under 1.3 V in Co/TiO2 multilayer granular films. The robust endurance with more than 5000 cycles is demonstrated. Similar phenomena exist in Ni/TiO2 and Fe/TiO2 multilayer granular films, which shows its universality. The magnetic change of 107% in Ni/TiO2 underlines its potential in a voltage-driven ON-OFF magnetism. Such giant and reversible voltage control of magnetism can be ascribed to space-charge effect at the ferromagnetic metals/TiO2 interfaces, in which spin-polarized electrons are injected into the ferromagnetic metal layer with the adsorption of lithium-ions on the TiO2 surface. These results open the door for a promising method to modulate the magnetization in ferromagnetic metals, paving the way toward the development of ionic-magnetic-electric coupled applications.

Nonmetallic N/C Nanozyme Performs Continuous Consumption of Glu for Inhibition of Colorectal Cancer Cells.

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality. 5-Fluorouracil (5-FU) is the first choice for treatment of CRC, but it cannot avoid the negative effects from local high glucose (Glu) in tumor. Recently, 5-FU therapy has been combined with other treatment modalities for CRC synergistic therapy. Although these combination therapy strategies are more effective in cancer therapy, the toxicity side effects to the liver and cause metabolic acidosis still exist. Herein, we report an emerging amorphous honeycomb-like nitrogen-doped carbon (N/C) nanozyme with nicotinamide adenine dinucleotide (NADH) oxidase and catalase (CAT) activity and cascade it with natural glucose dehydrogenase (GDH) to realize NAD+ regeneration and further hyperglycemia management. In this case, by the coupling of N/C nanozyme with natural GDH to form a N/C-GDH system, the electron transfer route can switch from Glu to a common but limited electron receptor, i.e., NAD+ to ubiquitous large amounts of oxygen, achieving the purpose of sustainable consumption of Glu under NAD+ circulation and regeneration, and importantly escaping the generation of toxic H2O2. The combination of the N/C-GDH system and 5-FU on CRC cells was investigated to assess their synergistic bioeffects. Notably, our results showed that the N/C-GDH system and 5-FU in combination significantly suppress the proliferation of human colon cancer cells (HCT-116) by reducing the sugar level and induced apoptosis compared with either material or drug used alone. This work expands the nanozymes in blood Glu management as well as the promising cancer cell inhibition and provides the possibility of nonmetallic nanomaterials in the realization of effective treatment of cancer.

Revealing interfacial space charge storage of Li+/Na+/K+ by operando magnetometry.

Interfacial space charge storage between ionic and electronic conductor is a promising scheme to further improve energy and power density of alkali metal ion batteries (AMIBs). However, the general behavior of space charge storage in AMIBs has been less investigated experimentally, mostly due to the complicated electrochemical behavior and lack of proper characterization techniques. Here, we use operando magnetometry to verify that in FeSe2 AMIBs, abundant Li+/Na+/K+ (M+) can be stored at M2Se phase while electrons accumulate at Fe nanoparticles, forming interfacial space charge layers. Magnetic and dynamics tests further demonstrate that with increasing ionic radius from Li+, Na+ to K+, the reaction kinetics can be hindered, resulting in limited Fe formation and reduced space charge storage capacity. This work lays solid foundation for studying the complex interfacial effect in electrochemical processes and designing advanced energy storage devices with substantial capacity and considerable power density.

Effects of Lactobacillus plantarum and Pediococcus acidilactici co-fermented feed on growth performance and gut microbiota of nursery pigs.

The fermented feed has been used extensively as a growth promoter in agricultural animal production. However, the effects of fermented feed on swine gut microbiota are still largely unknown. The work presented here aimed to investigate the growth performance and gut microbiota of nursery pigs receiving the LPF diet (10% Lactobacillus plantarum and Pediococcus acidilactici co-fermented feed + basal diet) compared with pigs receiving the NC diet (basal diet). The data showed LPF diet numerically improved average daily gain and significantly increased fecal acetate, butyrate, and total short-chain fatty acid (SCFA) concentrations. Furthermore, gut microbiota structure and membership significantly changed in response to the addition of fermented feed in the diet. Gut microbiota results indicated that LPF treatment significantly enriched SCFA-producing bacteria such as Megasphaera, Roseburia, Faecalibacterium, Blautia, Selenomonas, Dialister, Acidaminococcus, Ruminococcus, and Bifidobacterium. Some of these bacteria also had anti-inflammatory and other beneficial functions. Overall, these findings suggested that Lactobacillus plantarum and Pediococcus acidilactici co-fermented feed benefited growth performance and established potential health impacts on the gut microbiota of nursery pigs.

USP5-Beclin 1 axis overrides p53-dependent senescence and drives Kras-induced tumorigenicity.

Non-small cell lung cancers (NSCLC) frequently contain KRAS mutation but retain wild-type TP53. Abundant senescent cells are observed in premalignant but not in malignant tumors derived from the Kras-driven mouse model, suggesting that KRAS oncogenic signaling would have to overcome the intrinsic senescence burden for cancer progression. Here, we show that the nuclear Beclin 1-mediated inhibition of p53-dependent senescence drives Kras-mediated tumorigenesis. KRAS activates USP5 to stabilize nuclear Beclin 1, leading to MDM2-mediated p53 protein instability. KrasG12D mice lacking Beclin 1 display retarded lung tumor growth. Knockdown of USP5 or knockout of Becn1 leads to increased senescence and reduced autophagy. Mechanistically, KRAS elevates ROS to induce USP5 homodimer formation by forming the C195 disulfide bond, resulting in stabilization and activation of USP5. Together, these results demonstrate that activation of the USP5-Beclin 1 axis is pivotal in overriding intrinsic p53-dependent senescence in Kras-driven lung cancer development.

Neuroform atlas stent-assisted coiling of tiny wide-necked intracranial aneurysms.

Objective: To investigate the safety and efficacy of Neuroform Atlas stent-assisted coiling for the treatment of tiny wide-necked intracranial aneurysms and evaluate risk factors associated with procedure-related complications. Methods: We retrospectively examined 46 patients with 46 tiny wide-necked aneurysms who were treated using Atlas stent-assisted coiling at our institution from August 2020 to May 2022. Patient and aneurysm characteristics, procedural details, procedure-related complications, and angiographic and clinical outcomes were analyzed. Results: A total of 10 patients presented with aneurysmal rupture. Atlas stent placement was successful in all patients. Angiography immediately after the procedure showed complete occlusion in 38 patients (82.6%), neck remnant in 7 (15.2%), and partial occlusion in 1 (2.2%). The mean angiographic follow-up was 8.4 months (range, 6-16). At the last follow-up, angiography showed complete occlusion in 41 patients (89.1%) and neck remnant in 5 (10.9%). No aneurysm recurrence or in-stent stenosis occurred. Incidence of procedure-related complications was 10.8% (intraprocedural aneurysm rupture, two cases; acute thrombosis, two cases; and coil migration, one case); only one patient (2.2%) experienced procedural neurological morbidity. The mean clinical follow-up was 9.7 months. A favorable outcome was achieved in 45 patients (97.8%). In univariate logistic regression analysis, aneurysm size (odds ratio, 4.538; P = 0.045) was significantly associated with procedure-related complications. However, multivariate analysis found no independent risk factors. Conclusion: Atlas stent-assisted coiling of tiny wide-necked intracranial aneurysms is feasible and effective. Outcomes and occlusion rates are favorable and morbidity is low. The complication rate may be higher in larger tiny aneurysms.

Ominous T-Wave Changes in an Older Adult With Chest Pain.

This case report describes a patient in their 60s who presented to the emergency department with acute, severe precordial chest pain radiating to their left arm at night, accompanied by dyspnea, dizziness, and sweating.

Buried Interface Regulation by Bio-Functional Molecules for Efficient and Stable Planar Perovskite Solar Cells.

Among the factors that lead to the reduction of the efficiency of perovskite solar cell (PSCs), is the difficulty involved in realizing a high-quality film and the efficient charge transfer that take place at the interface between electron-transport layer (ETL) and perovskite. Here, we demonstrated a strategy for planar-type devices by natural bio-functional interfaces that uses a buried electron-transport layer made of cobalamin complexed tin oxide (SnO2@B12). As systematically investigating the effects of SnO2@B12 interfacial layer in perovskite solar cells, cobalamin can chemically link SnO2 layer and perovskite layer, resulting in improved perovskite film quality and interfacial defect passivation. Utilizing SnO2@B12 improves the efficiency of planar-type PSCs by 20.60 %. Furthermore, after 250 hours of exposure to an ambient atmosphere, unsealed PSCs containing SnO2@B12 degrade by 10%. This research provides a viable method for developing bio-functional molecules that will increase the effectiveness and durability of planar-perovskite solar cells.

Urine metabolomic characteristics of female patients with occupational chronic cadmium poisoning after 15 years of treatment.

Occupational chronic cadmium poisoning (OCCP) can cause irreversible organ damage. Currently, no effective treatment is available for OCCP, and effective and sensitive biomarkers for treatment evaluation are still lacking. In this study, metabolomics techniques were used to analyze changes in endogenous metabolites in the urine of patients with OCCP after 15 years of treatment. Thirty urine samples from female patients with OCCP and healthy female controls (n = 15 per group) were assessed using gas chromatography-time-of-flight mass spectrometry and ultra-high-performance liquid chromatography-Q-Exactive mass spectrometry. The OCCP group had higher concentrations of blood urea nitrogen and urinary cadmium but near-normal urinary concentrations of ß2 -microglobulin and retinol-binding protein. Compared with the control group, the OCCP group had 66 significantly different metabolites with a variable importance in projection score >1 and p < 0.05. These differential metabolites were involved in various metabolic pathways, such as creatine metabolism, nicotinate and nicotinamide metabolism, the pentose phosphate pathway, d-glutamine and d-glutamate metabolism, and amino acid metabolism. Compared with the control group, the OCCP group had significantly higher urinary concentrations of creatine, glutamic acid, quinolinic acid and nicotinic acid. In a receiver operator characteristic analysis, the area under the curve of creatine was higher than those for glutamic acid, quinolinic acid and nicotinic acid, indicating that urinary concentrations of creatine could be used as a sensitive biomarker for the diagnosis and prognosis of OCCP and for monitoring its treatment.