ObjectiveTo examine the impact of Toll-like receptor 4 （TLR4）-mediated neutrophil extracellular traps （NETs） formation on isoproterenol （ISO）-induced heart failure （HF） in aged mice. MethodsThe mice were randomly divided into Control group， Model group， TAK-242 （TLR4 inhibitor） group， LPS （TLR4 agonist） group and LPS+DNaseⅠ （NETs inhibitor） group， with 8 mice in each group. The HF model was established by continuous infusion of ISO through an osmotic pump， and TAK-242， LPS， and LPS+DNaseⅠ interventions were administered during the last week of infusion for 7 consecutive days. ELISA was used to detect the N-terminal pro-B-type natriuretic peptide （NT-pro BNP）， cardiac troponin I （cTnI）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and serum and myocardial tissue myeloperoxidase-DNA （MPO-DNA） and neutrophil elastase-DNA （NE-DNA） levels. HE staining was used to observe the pathological changes of myocardial tissue. Masson staining was used to observe the deposition of collagen fibers in myocardial tissue. Immunofluorescence was used to observe the colocalization of Ly6G and MPO in myocardial tissue. The protein expressions of TLR4， MPO， NE and cit-H3 in myocardial tissue were detected by Western blot. ResultsCompared with the Control group， the end-diastolic interventricular septal thickness （IVSD）， left ventricular end-diastolic diameter （LVEDD） and left ventricular end-systolic diameter （LVESD） in the Mode group significantly increased （P<0.01）， fractional shortening （FS） and ejection fraction （EF） significantly decreased （P<0.01）， and the myocardial structure was significantly damaged. The myocardial collagen fiber precipitation， serum NT-pro BNP， cTnI， IL-1β， IL-6 and TNF-α contents， MPO-DNA and NE-DNA contents in serum and myocardial tissue significantly increased （P<0.01）. The co-localization of Ly6G and MPO and the expression of TLR4， MPO， NE and cit-H3 proteins in myocardial tissue significantly increased （P<0.01）. After TAK-242 intervention， the above indicators were significantly reversed， while the injury was further aggravated in LPS group. DNaseⅠ treatment could partially alleviate the deterioration of myocardial structure and function induced by LPS. ConclusionTLR4 and NETs are abnormally elevated in the myocardial tissue of aged HF mice. Treatment with the TLR4 inhibitor TAK-242 effectively suppresses NET formation， attenuates inflammatory responses， and enhances cardiac function in aged HF mice.

To investigate the protective effect of Lycium barbarum glycopeptide(LbGp)on testicu-lar injury induced by D-galactose(D-gal)in aging rats,male SD rats were randomly divided into 6 groups:the blank control group(Control),aging model group(Model),positive control group(β-nicotinamide mononucleotide,NMN),low dose LbGp group(LLbGp),medium dose LbGp group(MLbGp)and high dose LbGp group(HLbGp).The testicular mass of rats was counted,the morphological changes of testicular tissue were observed by hematoxylin-eosin(HE)staining,the testicular senescence was detected by β-galactosidase(SA-β-gal)staining,and the levels of testos-terone(T),luteinizing hormone(LH)and follicle stimulating hormone(FSH)in serum were de-tected.The levels of oxidative factors such as glutathione peroxidase(GSH-Px),superoxide dis-mutase(SOD),malondialdehyde(MDA),catalase(CAT)and inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in rat tissues were measured.TUNEL staining was used to detect the apoptosis of testicular cells,epididymal sperm quality,and the expression of Keap1,Nrf2 and Nqo1 mRNA were analyzed.The results showed that compared with the Model group,the testicular coefficient of Lycium barbarum glycopeptide rats in MLbGp and HLbGp groups increased(P＜0.01),the level of T in serum and sperm quality increased(P＜0.05),the structural degeneration and aging of testicular tissue decreased(P＜0.01),the level of antioxidant factors increased,and the levels of inflammatory factors and apopto-sis decreased(P＜0.05).The expression of Keap1 decreased significantly(P＜0.01),while the ex-pression of Nrf2 and Nqo1 mRNA increased(P＜0.05).The above results indicate that Lycium barbarum glycopeptide can improve D-gal-induced testicular senescence,attenuate oxidative stress,reduce inflammatory response,decrease apoptosis,and exert a protective effect on testicular injury in rats due to senescence through the Keap1-Nrf2 signaling pathway.

Automotive antifreeze, being colorless and odorless, can easily cause acute poisoning if ingested. Acute poisoning can lead to damage to the central nervous system, digestive system, and kidney function, and may even result in death. This article analyzes the clinical data, diagnostic and therapeutic processes, and outcomes of two patients admitted to the Department of Poisoning and Occupational Diseases, Emergency Medicine of Qilu Hospital, Shandong University, who suffered acute poisoning due to ingesting antifreeze. The findings aim to provide a reference for clinicians in the diagnosis and treatment of antifreeze poisoning.

This article analyzes the treatment process of a patient with respiratory failure caused by occupational acute acetonitrile poisoning. Due to operational errors, the patient's body was sprayed with a large amount of acetonitrile liquid, leading to the absorption of acetonitrile through the skin and resulting in acute poisoning. The clinical manifestations were nervous system and respiratory system damage, accompanied by severe lactic acidosis. After active comprehensive treatments such as tracheal intubation, mechanical ventilation, continuous renal replacement therapy (CRRT) , and glucocorticoids, the patient basically recovered. The treatment process of this patient indicates that early identification and correct first aid of acetonitrile poisoning are the keys to improving prognosis and can provide a reference for the handling of similar clinical cases.

Objective:Exploring the association between Life's Crucial 9 (LC9) and the risk of thyroid dysfunction (TD), as well as its potential predictive capacity.Methods:A total of 247 600 TD-free participants from the UK Biobank were enrolled in the study. The LC9 score was divided into three CVH groups: low (0-), medium (50-), and high (80-100). Cox proportional hazards regression models were used to calculate the HRs and 95% CIs of the risk of TD with LC9 CVH status. Calculate Harrell's concordance index ( C-index), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to evaluate the predictive ability of the LC9 score and Life's Essential 8 (LE8) score. Results:During a median follow-up of 12.3 years, 5 515, 911, and 4 869 new cases of TD, hyperthyroidism, and hypothyroidism were documented, respectively. Participants with a high LE8 CVH group had 57.00% ( HR=0.43, 95% CI: 0.38-0.49), 55.00% ( HR=0.45, 95% CI: 0.34-0.60), and 58.00% ( HR=0.42, 95% CI: 0.37-0.47) lower risk of TD, hyperthyroidism, and hypothyroidism, respectively, than those with low CVH group. Compared with the LE8 score, the improvement in C-index for the LC9 score predicted TD risk was 0.004 (95% CI: 0.001-0.007), the NRI was 0.101 (95% CI: 0.021-0.103), and the IDI was 0.001 (95% CI: 0.000-0.001). Conclusions:The better CVH status, defined by LC9, was associated with a lower risk of TD. Compared to the LE8 score, the LC9 score demonstrated a significant enhancement in both risk discrimination and reclassification capability for TD risk.

Objective:To compare the relative proportion of direct action (ray particles directly destroy biological molecules such as DNA and indirect action (radical-mediated oxidative damage) in the damage caused by X-ray and proton irradiation of lung cancer cells.Methods:Unirradiated human lung adenocarcinoma A549 cells and human large cell lung cancer NCI-H460 cells were cultured in media containing 0, 0.125, 0.25, 0.5, 0.75 mol/L dimethyl sulfoxide (DMSO) for 1 h to obtain plating efficiency (PE) values, thereby determining whether DMSO affected cell survival. Following pretreatment with each DMSO concentration, cells were exposed to X-ray irradiation at physical doses of 2, 4, 6, 8 Gy and proton irradiation at equivalent doses of 2, 4, 6, 8 GyE, respectively. Survival fractions (SF) and maximum protection (MP) values were calculated to evaluate the effects of varying DMSO concentrations on post-irradiation cell survival and to quantify the contribution of indirect radiation damage mechanisms (higher MP indicates greater indirect effect contribution). PE, SF, and MP values were determined using clonogenic assays. Comparisons among multiple groups were performed using one-way ANOVA followed by Tukey's multiple comparison, and comparisons between irradiation groups were analyzed using independent samples t-tests. Results:The PE of unirradiated cells treated with varying DMSO concentrations showed no statistically significant differences. Following pretreatment at different DMSO concentrations and subsequent irradiation with X-rays or protons, the protective effect of DMSO reached saturation at 0.5 mol/L. At this concentration, comparison of the average MP values across 4 radiation doses revealed: In A549 cells, the MP value was 54.21%±1.73% for X-ray irradiation group and 39.69%±0.72% for proton irradiation group ( t=16.82, P<0.001); in NCI-H460 cells, the MP value was 52.04%±1.00% for X-ray irradiation group and 41.31%±0.70% for proton irradiation group ( t=10.19, P<0.001). Conclusions:Under biologically equivalent doses, proton irradiation demonstrates greater reliance on direct effects in lung cancer cells killing compared with X-ray irradiation.

Objective The athletic performance and physiological indicators of two top seated cross-country skiers during simulated competitions were analyzed,and the characteristics of exercise intensity and pacing strategies in different terrains were explored,so as to provide a scientific basis for physical fitness allocation and speed rhythm optimization of the athletes.Methods Differential global positioning system and Momentum Technology MT-Sports T2 were used to test athlete A and athlete B with class of locomotor winter 10(LW 10),who were the first and second runners-up of Beijing Winter Paralympic mid-distance cross-country ski race.The athletes' real-time gliding speed and heart rate during five consecutive 15 km cross-country skiing time trials were collected,and the time spent on each section,speed and heart rate changes in each course were analyzed.Results The coefficient of variation(CV)of mean heart rate on uphill and flat terrain sections were significantly correlated with total scores.The average gliding speed and average heart rate as a percentage of maximum heart rate(HRmax)of the athletes in three terrains were significantly correlated with total scores.The correlation between the mean time spent on uphill and flat terrain and total performance was stronger than that between the mean time spent on downhill terrain and total scores.Both athletes used a cumulative acceleration speed rhythm.Conclusions Uphill and flat terrain time are critical to race performance.Athletes adopt a progressive pacing strategy,gradually increasing speed in the first half,maintaining stable output in the mid-race,and finishing the last lap at a high-speed.Heart rates are mainly distributed between 70％-90％HRmax,and balancing high-intensity efforts on uphills with recovery on downhills helps optimize energy expenditure.

To investigate the protective effect of Lycium barbarum glycopeptide(LbGp)on testicu-lar injury induced by D-galactose(D-gal)in aging rats,male SD rats were randomly divided into 6 groups:the blank control group(Control),aging model group(Model),positive control group(β-nicotinamide mononucleotide,NMN),low dose LbGp group(LLbGp),medium dose LbGp group(MLbGp)and high dose LbGp group(HLbGp).The testicular mass of rats was counted,the morphological changes of testicular tissue were observed by hematoxylin-eosin(HE)staining,the testicular senescence was detected by β-galactosidase(SA-β-gal)staining,and the levels of testos-terone(T),luteinizing hormone(LH)and follicle stimulating hormone(FSH)in serum were de-tected.The levels of oxidative factors such as glutathione peroxidase(GSH-Px),superoxide dis-mutase(SOD),malondialdehyde(MDA),catalase(CAT)and inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in rat tissues were measured.TUNEL staining was used to detect the apoptosis of testicular cells,epididymal sperm quality,and the expression of Keap1,Nrf2 and Nqo1 mRNA were analyzed.The results showed that compared with the Model group,the testicular coefficient of Lycium barbarum glycopeptide rats in MLbGp and HLbGp groups increased(P＜0.01),the level of T in serum and sperm quality increased(P＜0.05),the structural degeneration and aging of testicular tissue decreased(P＜0.01),the level of antioxidant factors increased,and the levels of inflammatory factors and apopto-sis decreased(P＜0.05).The expression of Keap1 decreased significantly(P＜0.01),while the ex-pression of Nrf2 and Nqo1 mRNA increased(P＜0.05).The above results indicate that Lycium barbarum glycopeptide can improve D-gal-induced testicular senescence,attenuate oxidative stress,reduce inflammatory response,decrease apoptosis,and exert a protective effect on testicular injury in rats due to senescence through the Keap1-Nrf2 signaling pathway.

Objective:To develop a laser-induced graphene (LIG)-based multimodal electrochemical sensor for monitoring the burn wound microenvironment and to evaluate its performance.Methods:This study was an experimental study. LIG three-electrode substrates were functionalized with L-lactate oxidase, polyaniline, and sortase A to fabricate lactate sensor, pH sensor, and bacterial sensor, respectively, thereby constituting the LIG-based multimodal electrochemical sensor. An electrochemical workstation was used to assess the electrochemical performance of the lactate sensor and bacterial sensor by cyclic voltammetry, with voltammetric response curves being plotted. An electrochemical workstation was used to assess the lactate sensor's response to lactate by chronoamperometry (with current-time curve being recorded and calibration curve being plotted during the test in the L-lactic acid solution with a molar concentration of 10-60 mmol/L), the pH sensor's response to pH by open-circuit potential measurement (with open-circuit potential-time curve being recorded and calibration curve being plotted during the test in the standard buffer solutions with pH values ranging from 3 to 8), and the bacterial sensor's response to bacteria by differential pulse voltammetry (with current-voltage curve being recorded and calibration curve being plotted during the test in gradient suspensions of Staphylococcus aureus ranging from 1×103-1×10? colony forming unit (CFU)/mL). The sample size for all the above experiments was 3. The correlation analysis was performed on the current value of the lactate sensor and the lactate concentration, the average value of steady-state open circuit potential of the pH sensor and the pH value, and the peak current value of the bacterial sensor and the bacterial concentration value. Each of the prepared standard test system solutions for lactate, pH value, and bacteria were all aliquoted into 30 samples. The lactate concentration, pH value, and bacterial concentration were determined by the lactate sensor and a L-lactate assay kit, the pH sensor and a precision pH meter, and the bacterial sensor and a microvolume spectrophotometer, respectively. Fifteen pairs of matched data were selected according to the random number table method for comparison, and the correlation analysis was performed on the measured values of each sensor and the reference values of the corresponding standard methods. Results:The voltammetric response curves showed that the lactate sensor and the bacterial sensor exhibited distinct oxidation peak currents at oxidation peak potentials of approximately 0.74 and 0.65 V, respectively. In the lactate sensor, the change in current after addition of phosphate buffered solution was (0.025±0.041) μA, which was significantly lower than that after addition of L-lactate solution (0.228±0.117) μA ( t=2.85, P<0.05). In the L-lactic acid solution with a molar concentration of 10-60 mmol/L, the current value of the lactate sensor was significantly linearly correlated with the lactate concentration ( r=0.98, P<0.05). In the standard buffer solutions with pH values ranging from 3 to 8, the average value of steady-state open circuit potential of the pH sensor was significantly linearly correlated with the corresponding pH values ( r=0.96, P<0.05). In gradient suspensions of Staphylococcus aureus ranging from 1×103 to 1×10? CFU/mL, the peak current value of the bacterial sensor was significantly linearly correlated with the logarithm of bacterial concentration ( r=0.95, P<0.05). There were no statistically significant differences between the lactate concentrations measured by the lactate sensor and by the L-lactate assay kit, pH values measured by the pH sensor and by the precision pH meter, and logarithmic bacterial concentrations measured by the bacterial sensor and by the microvolume spectrophotometer ( P>0.05), but there were significant positive correlations between the two (with r values of 0.97, 0.96, and 0.95, respectively, P<0.05). Conclusions:After functional modification, the developed LIG-based multimodal electrochemical sensor enables accurate monitoring of lactate concentration, pH value, and bacterial load in the burn wound microenvironment with the results being of high sensitivity and stability. This platform provides a reliable new approach for non-invasive monitoring of the critical indicators of burn wound microenvironment, which shows great prospects for clinical application.

This study reviews recent publications on the biomechanical causes and treatment of flat foot,through searching PubMed,Web of Science,CNKI,Wanfang and other databases.The reasons for the formation of flat foot include congenital factors and acquired factors,while the treatment methods mainly include orthopedic insoles,physical therapy,surgical therapy and exercise therapy.These methods,to a certain extent,can correct foot structural abnormalities,optimize biomechanical properties and improve foot stability and range of motion.For future research,the advanced imaging and simulation technology will be used for accurate assessment,the application of novel materials and non-surgical therapies will relieve long-term symptoms,genetic researches will promote the development of early diagnosis and personalized treatment,and the use of intelligent orthosis will realize real-time monitoring and dynamic adjustment,to provide more and more effective methods and means for the evaluation,intervention and treatment of flat foot.