Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective:To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice.Methods:This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed.Results:A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up.Conclusions:MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.

OBJECTIVE To explore the distribution of airborne pollen in Cangzhou,to analyze the correlation between pollen characteristics,meteorological factors and the rate of allergic rhinitis visits,and to provide a reference basis for the precise prevention and treatment of allergic rhinitis in Cangzhou.METHODS The gravity deposition method was applied to collect daily airborne pollen from the monitoring sites in Cangzhou from March to October 2022 and record the pollen species and quantities.We also collected information on allergic rhinitis patients who visited the ENT Department of Cangzhou Central Hospital during the same period and meteorological data(daily maximum temperature,minimum temperature,maximum relative humidity,maximum precipitation,and maximum wind speed at ground level)during the same period,and analyzed the relationship between the number of AR patients'visits,the amount of pollen,and the meteorological factors.RESULTS 1.A total of 229 pollen exposures were collected from March to October 2022,totaling 19 368 pollen grains,of which 18 750 grains of pollen could be identified in 19 families and 618 grains were difficult to identify the families.2.There were two peaks of pollen during the period,in April and September respectively.Spring pollen to tree-based category,to the pine family,willow willow family,Xylariaceae(ash)most often;summer pollen volume has declined,but still tree-based category;fall pollen to herbaceous category,to the Asteraceae Artemisia,mulberry,Gramineae most often.3.The pollen concentration in Cangzhou City was negatively correlated with maximum humidity,maximum precipitation,maximum temperature,and minimum temperature.Maximum wind speed at ground level was positively correlated with pollen concentration.4.Pollen concentration was positively correlated with the number of visits.The correlation analysis between daily medical visits from June to October and air pollen concentration showed a significant positive correlation,while the results from March to May showed no significant correlation.CONCLUSION The peak of airborne pollen dispersal in April and September in Cangzhou.Spring and summer pollen is dominated by tree species,and the dominant pollen is Pinaceae,Willow genus of Populus,and Xylariaceae(ash genus);fall pollen is dominated by herbaceous species,and the dominant pollen is Artemisia,Asteraceae,Mulberry,and Gramineae.Meteorological factors are important factors affecting pollen concentration.Within a certain range,the lower the maximum humidity,the lowest maximum precipitation,the lower the highest or the lowest temperature,the higher the pollen concentration,and the pollen concentration is more affected by the lowest temperature.There is a correlation between pollen concentration and the number of AR patients'visits from June to October,which can be used as an environmental early warning indicator of the prevalence of AR.

BACKGROUND:Pulsed electromagnetic fields,as an important physical therapy,are exactly effective in the treatment of osteoarthritis,but the mechanism has not been fully clarified. OBJECTIVE:To observe the effect of pulsed electromagnetic field on the degeneration of knee joint cartilage in aged rats. METHODS:Eight 6-month-old Sprague-Dawley rats were selected as the young group and were subjected to normal diet with no treatment.Sixteen 22-month-old Sprague-Dawley rats were randomly divided into old group(n=8)and pulsed electromagnetic field group(n=8).The rats in the pulsed electromagnetic field group were subjected to a pulsed electromagnetic field intervention,once a day,5 days per week for continuous 8 weeks.The rats in the old group were given no treatment.All rats were anesthetized and executed after 8 weeks for the detection of relevant indexes. RESULTS AND CONCLUSION:Compared with the young group,serum type Ⅱ collagen C-terminal peptide level was increased in the old group(P<0.05);compared with the old group,serum type Ⅱ collagen C-terminal peptide level was decreased in the pulsed electromagnetic field group(P<0.05).Micro-CT showed that the bone volume fraction,bone mineral density,and number of bone trabeculae decreased(P<0.05)and the trabecular separation increased(P<0.05)in the tibia of rats in the aged group compared with the young group;and the bone volume fraction,bone density,and number of trabeculae increased(P<0.05)and the trabecular separation decreased(P<0.05)in the tibia of rats in the pulsed electromagnetic field group compared with the aged group.The tibial plateau Safranin O-fast green staining showed that the articular cartilage structure of rats in the aged group was disorganized,and the number of chondrocytes was obviously reduced,and the tidal line could not be distinguished.The above results were improved in the pulsed electromagnetic field group.RT-qPCR and western blot assay showed that the mRNA and protein expression levels of matrix metalloproteinase 1,matrix metalloproteinase 13,P53 and P21 in the articular cartilage and subchondral bone of rats were elevated in the aged group compared with the young group(P<0.05)and decreased in the pulsed electromagnetic field group compared with the old group(P<0.05).To conclude,pulsed electromagnetic fields may improve osteoarthritis in aged rats by inhibiting chondrocyte senescence,alleviating articular cartilage degradation and inhibiting subchondral bone osteoporosis through suppressing the expression of P53/P21.

Objective:To explore the application value of 3D-slicer software in measuring renal volume parameters of renal transplant donors in evaluating renal function.Methods:The data of 31 renal donors admitted to Beijing Friendship Hospital, Capital Medical University from October 2019 to September 2022 were retrospectively analyzed. Glomerular filtration rate (GFR) were measured by SPECT radioactive dynamic imaging, and renal cortex volume (RCV), renal parenchymal volume (RPV) were measured after 3D reconstruction of urinary enhanced CT based on 3D slicer software. The estimated GFR(eGFR) predicted by creatinine-based GFR estimation equations (C-G equation, modified and simplified MDRD equation) and volume-based GFR estimation equations (Herts equation, Choi equation). Different eGFR were calculated, and the correlation between kidney volume parameters, eGFR equations and measured GFR was analyzed. The deviation, accuracy and consistency between different equations eGFR and measured GFR were analyzed and compared. The measurement data of normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for inter-group comparison. Measurement data with non-normal distribution were represented by M( Q1, Q3), and non-parametric test was used for comparison between groups. Results:The correlation between different eGFR and measured GFR is poor, and the deviation is small, and with good accuracy and consistency. Except for the weak correlation between the Choi equation eGFR and measured GFR ( r=0.382, P=0.034), there was no significant correlation between eGFR by other equations and measured GFR ( P>0.05). Among them, the deviation between the Herts equation-eGFR and measured GFR was the smallest (0.30 mL·min -1·1.73 m -2), with a 10% coincidence rate (61.29%) and a 30% coincidence rate (96.77%), and the best consistency with measured GFR, with a consistency limit of -28.75 to 29.34 mL·min -1·1.73 m -2. Conclusion:Compared with the laboratory index formula method, the Herts equation has better prediction efficiency in estimating GFR, The measurement of renal volume parameters by 3D slicer software has a certain clinical value in evaluating the renal function of renal donors, which is worthy of further application.

Objective:To investigate the alterations of brain functional network related to disease progression in patients with temporal lobe epilepsy (TLE) and the potential neural mechanism of executive dysfunction.Methods:Nineteen temporal lobe epilepsy patients with a disease course of less than or equal to 5 years (TLE-SD group) and 24 temporal lobe epilepsy patients with a disease course of more than 5 years (TLE-LD group) were recruited from the Epilepsy Clinic of the First Affiliated Hospital of Guangxi Medical University from December 2019 to December 2021. At the same time, 21 healthy control individuals (healthy control group) were recruited from the society and matched with gender, age, and education level. All subjects were evaluated demographic and clinical data, and performed resting state functional magnetic resonance imaging (rs-fMRI) and attention network test (ANT). The topological properties of functional brain network of 3 groups of subjects were calculated using graph theory, and then the hubs were determined. Then the inter-group comparison of hubs properties was carried out, and the correlation analysis with executive control function was performed.Results:The distribution pattern of hub nodes in TLE-SD patients was changed. Compared with the TLE-LD and healthy control groups, the TLE-SD group significantly increased the nodal degree values in brain regions such as the ventrolateral area of the left middle frontal gyrus, the left anterior central gyrus (upper limb area), the cephalic and caudal areas of the left parietal lobule, as well as the inner parietal lobe area, the caudal side of the right parietal lobule, and the right lateral occipital cortex. The nodal values of the brain areas such as the lateral and parietal inner area, the caudal side of the right upper upper lobule, and the right lateral occipital cortex were significantly increased. TLE-SD patients had a significant increase in the middle of the right upper frontal gyrus and the head of the left upper upper lobule. The node efficiency was significantly lower than that of TLE-LD patients, and the node efficiency in the middle of the right upper frontal gyrus was significantly lower than that of the healthy control group. The node network attributes of the left upper lobe were positively correlated with the execution control efficiency, and negatively correlated with the orientation efficiency. No significant difference was detected between TLE-LD patients and healthy controls.Conclusions:In TLE patients, the hubs in the middle of the right superior frontal gyrus were first damaged, and new hubs appeared in the dorsal attention network, the left anterior central gyrus and the right occipital lobe and were overloaded. With the progression of the disease, hubs tended to be redistributed to normality. The left superior parietal lobule may play an important role in the impairment of executive control function in TLE patients.

Objective:The study aimed to investigate the association between lesion location and post-stroke depression (PSD) in acute ischemic stroke patients.Methods:In this case-control study, acute ischemic stroke patients were recruited from the Department of Neurology, First Affiliated Hospital of the University of Science and Technology of China (USTC), between September 2020 and June 2021. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, the patients were divided into the PSD and non-PSD groups. The 24-item Hamilton Rating Scale (HAMD) was used to evaluate the severity of depression. The Student′s t-test, Mann-Whitney test, and Chi-square test were used to compare the clinical baseline characteristics of PSD and non-PSD groups. Voxel-based lesion-symptom mapping (VLSM) was applied to investigate the association between lesion location and depression occurrence and severity. Results:A total of 70 and 173 patients were admitted to the PSD and non-PSD groups, respectively. The mean age of patients was 59 years (23-86). There were 153 males and 90 females. Univariate analysis showed a significant difference only in Hamilton Anxiety ( P=0.025) and Depression ( P<0.001) scores between the PSD and non-PSD groups. VLSM analysis identified clusters within the anterior cingulate gyrus ( Z=-3.05, P<0.001), left hippocampus ( Z=-3.15, P<0.001), and left lingual lobe ( Z=-3.08, P<0.001) where lesions were significantly associated with PSD. Additionally, the severity of PSD was associated with damage in the anterior cingulate gyrus ( Z=-3.64, P<0.001), left hippocampus ( Z=-3.51, P<0.001), left lingual lobe ( Z=-4.18, P<0.001), and pericalcarine cortex ( Z=-3.65, P<0.001). Conclusion:VLSM demonstrated that lesion location could be used to predict the occurrence of PSD in patients with acute ischemic stroke.

Engineered probiotics can serve as therapeutics based on their ability of produce recombinant immune-stimulating properties. In this study, we built the recombinant Bacillus subtilis WB800 expressing antimicrobial peptide KR32 (WB800-KR32) using genetic engineering methods and investigated its protective effects of nuclear factor-E2-related factor 2 (Nrf2)‍-Kelch-like ECH-associated protein 1 (Keap1) pathway activation in intestinal oxidative disturbance induced by enterotoxigenic Escherichia coli (ETEC) K88 in weaned piglets. Twenty-eight weaned piglets were randomly distributed into four treatment groups with seven replicates fed with a basal diet. The feed of the control group (CON) was infused with normal sterilized saline; meanwhile, the ETEC, ETEC+WB800, and ETEC+WB800-KR32 groups were orally administered normal sterilized saline, 5×10¹⁰ CFU (CFU: colony forming units) WB800, and 5×10¹⁰ CFU WB800-KR32, respectively, on Days 1‍‒‍14 and all infused with ETEC K88 1×10¹⁰ CFU on Days 15‍‒‍17. The results showed that pretreatment with WB800-KR32 attenuated ETEC-induced intestinal disturbance, improved the mucosal activity of antioxidant enzyme (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) and decreased the content of malondialdehyde (MDA). More importantly, WB800-KR32 downregulated genes involved in antioxidant defense (GPx and SOD1). Interestingly, WB800-KR32 upregulated the protein expression of Nrf2 and downregulated the protein expression of Keap1 in the ileum. WB800-KR32 markedly changed the richness estimators (Ace and Chao) of gut microbiota and increased the abundance of Eubacterium_rectale_ATCC_33656 in the feces. The results suggested that WB800-KR32 may alleviate ETEC-induced intestinal oxidative injury through the Nrf2-Keap1 pathway, providing a new perspective for WB800-KR32 as potential therapeutics to regulate intestinal oxidative disturbance in ETEC K88 infection.
Animals ; Swine ; Enterotoxigenic Escherichia coli ; Kelch-Like ECH-Associated Protein 1 ; Bacillus subtilis ; NF-E2-Related Factor 2 ; Antioxidants ; Oxidative Stress

Objective:To investigate the application value of three-dimensional image reconstruction technology based on 3D-slicer software in urology.Methods:The data of 36 patients with urinary tract diseases admitted to Beijing Friendship Hospital, Capital Medical University from May 2019 to December 2021 were retrospectively analyzed, including 20 males and 16 females; the median age was 53.50(41.75, 66.25) years. There were 10 relative kidney transplant donors, 12 cases with renal tumors, 6 cases with hydronephrosis and 8 patients with urinary calculi. The CT urography data of 36 cases were reconstructed into three-dimensional image models based on 3D-slicer software, and the morphology of the target tissue was measured.Results:In the urinary system model of 10 relative kidney transplant donors constructed in this study, the type of donor renal artery was single artery in 7 cases and accessory renal artery in 3 cases; In the three-dimensional model of 12 tumor kidneys, 4 tumors were located at the upper part of the kidney (2 near ventral and 2 near dorsal), 5 tumors were located at the middle part of the kidney (2 near ventral and 3 near dorsal), and 3 tumors were located at the lower part of the kidney near ventral. The average maximum diameter of the tumors was (27.3 ± 9.63) mm, and the tumor volume was (15.89 ± 5.93) cm 2. The study also successfully constructed a three-dimensional image model of the urinary system in 6 patients with hydronephrosis and 8 patients with urinary calculi (without hydronephrosis). Three-dimensional model image reconstructed by 3D-slicer software clearly showed the spatial structure of renal parenchyma, blood vessels, renal pelvis, calyces and ureter. The diameter, position and direction of ureters and blood vessels can be observed clearly based on the three-dimensional reconstruction model, and clinicians could also evaluate the location, shape, size and adjacent relationship with surrounding tissues of renal cysts, tumors, stones or other masses. Conclusion:3D-slicer software platform can assist clinicians to reconstruct the three-dimensional model of urinary system, which is worthy of further clinical application.

Objective:To explore the differences of static and dynamic spontaneous brain activity between male smoking addicts and healthy controls, and analyze the mechanism of smoking addiction.Methods:Based on static amplitude of low-frequency fluctuation (sALFF) and dynamic amplitude of low frequency fluctuation (dALFF), the differences of static and dynamic spontaneous brain activity were compared between male smoking addicts ( n=63) and healthy controls ( n=30) by independent sample t-test. Pearson correlation analysis was used to investigate the relationships between the altered dALFF values and score of Fagerstr?m test for nicotine dependence(FTND) and pack-years of smoking addicted males. Results:Compared with healthy controls, the values of sALFF in the left superior/middle/inferior orbitofrontal gyrus ( t=5.17, clusters≥108) were increased and the variation of dALFF in the right superior temporal/middle gyrus, left orbitofrontal region, left orbital superior/middle/inferior frontal gyrus, right orbitofrontal gyrus/middle/inferior frontal gyrus and right putamen ( t=4.90, 4.37, 4.91, 4.62, 4.59, clusters≥96) were also increased in the smoking addicted group. It was noteworthy that the dALFF values of the right superior temporal/middle gyrus( r=0.252, P=0.047), left orbital region superior frontal gyrus( r=0.281, P=0.026) and right putamen( r=0.313, P=0.012) were positively correlated with pack-years of male smoking addicts. Conclusion:Male smoking addicts may have abnormal static and dynamics spontaneous neural activity in prefrontal cortex (including orbital frontal lobe), putamen and superior temporal/middle gyrus, which are correlated with pack-years.