Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective:To investigate the influence of contrast-enhanced computed tomography(CECT)on dose calculation in magnetic resonance imaging(MRI)-guided online adaptive radiotherapy(oART)based on the electron density(ED)assignment method for rectal cancer.Methods:A retrospective analysis was conducted on the medical data of 15 patients with locally advanced rectal cancer at middle-low segments,who admitted to the Chinese PLA General Hospital between December 2023 and April 2025.All patients underwent both plain computed tomography(PCT)and CECT scans during location.The average HU and ED value of all organs that were extracted from PCT and CECT images in the treatment plan system were obtained,and the influences of contrast agent of intake on image characteristics of the structure of each organ(small intestine,femoral head,bladder)were analyzed.PCT was used as referred image to design reference plan(Pref).The synthetic CT(sCT)was simulated and generated on the basis of PCT and CECT,respectively.The beam flow field that was same with Pref was used to recalculate dose on sCT,and then,the online plan(PPCT)based on PCT,and the online plan(PCECT)based on CECT were obtained,respectively,which can simulate the online dose calculation of MRI-guided online adaptive radiotherapy(oART).The Pref was used as reference to compare dosimetric parameters for target region and organ at risk(OAR)through dose volume histogram(DVH)and planed evaluation indicators.Additionally,three dimension(3D)slicer software was used to perform γ analysis for the results of dose distribution,and explore the differences among PPCT,PCECT and Pref on dose distribution.Results:In terms of image characteristics,the HU values of soft-tissue organs(intestine,bladder,spinal cord,soft tissue)and planning target volume(PTV)in CECT were higher than those in PCT,and the differences of them were statistically significant(Zintestines=-2.188,Zbladder=-3.196,tspinal cord=-3.767,tsoft tissue=-10.083,tPTV=-4.693,P<0.05),while its influence was less on bone tissue.The statistical results of ED were consistent with those of HU.Regarding to dosimetric parameters,there was no statistically significant difference in target coverage rate between PPCT and Pref(P>0.05),and the D50%of the PPCT[(2724.25±19.91)cGy]was higher than that of the Pref[(2718.99±21.13)cGy],and the difference was statistically significant(t=-3.679,P=0.002).However,the target coverage rate of PCECT was 94.65(94.04,95.27)%,and the difference of that between PCECT and Pref was statistically significant(Z=-2.158,P=0.031).For OAR,the differences of Dmax value of the small intestine,and the V20 of the left femoral head between PPCT and Pref were significant(Z=-2.556,-2.529,P<0.05).The differences of the Dmax of small intestine,and the D50%of bladder between PCECT and Pref were significant(t=-4.821,2.171,P<0.05).The comparative γ passed rates of PPCT,PCECT and Pref under the standards of 3 mm/3%and 2 mm/2%were all above 95%,and the differences were not significant(P>0.05).Conclusions:The influence of CECT on dose calculation in MRI-guided oART based on ED assignment method for rectal cancer is relatively small,which can be directly used in the design of reference plan,but the maximum dose of radiation-sensitive organs such as the small intestine should be paid attention.

Objective:To investigate the influence of contrast-enhanced computed tomography(CECT)on dose calculation in magnetic resonance imaging(MRI)-guided online adaptive radiotherapy(oART)based on the electron density(ED)assignment method for rectal cancer.Methods:A retrospective analysis was conducted on the medical data of 15 patients with locally advanced rectal cancer at middle-low segments,who admitted to the Chinese PLA General Hospital between December 2023 and April 2025.All patients underwent both plain computed tomography(PCT)and CECT scans during location.The average HU and ED value of all organs that were extracted from PCT and CECT images in the treatment plan system were obtained,and the influences of contrast agent of intake on image characteristics of the structure of each organ(small intestine,femoral head,bladder)were analyzed.PCT was used as referred image to design reference plan(Pref).The synthetic CT(sCT)was simulated and generated on the basis of PCT and CECT,respectively.The beam flow field that was same with Pref was used to recalculate dose on sCT,and then,the online plan(PPCT)based on PCT,and the online plan(PCECT)based on CECT were obtained,respectively,which can simulate the online dose calculation of MRI-guided online adaptive radiotherapy(oART).The Pref was used as reference to compare dosimetric parameters for target region and organ at risk(OAR)through dose volume histogram(DVH)and planed evaluation indicators.Additionally,three dimension(3D)slicer software was used to perform γ analysis for the results of dose distribution,and explore the differences among PPCT,PCECT and Pref on dose distribution.Results:In terms of image characteristics,the HU values of soft-tissue organs(intestine,bladder,spinal cord,soft tissue)and planning target volume(PTV)in CECT were higher than those in PCT,and the differences of them were statistically significant(Zintestines=-2.188,Zbladder=-3.196,tspinal cord=-3.767,tsoft tissue=-10.083,tPTV=-4.693,P<0.05),while its influence was less on bone tissue.The statistical results of ED were consistent with those of HU.Regarding to dosimetric parameters,there was no statistically significant difference in target coverage rate between PPCT and Pref(P>0.05),and the D50%of the PPCT[(2724.25±19.91)cGy]was higher than that of the Pref[(2718.99±21.13)cGy],and the difference was statistically significant(t=-3.679,P=0.002).However,the target coverage rate of PCECT was 94.65(94.04,95.27)%,and the difference of that between PCECT and Pref was statistically significant(Z=-2.158,P=0.031).For OAR,the differences of Dmax value of the small intestine,and the V20 of the left femoral head between PPCT and Pref were significant(Z=-2.556,-2.529,P<0.05).The differences of the Dmax of small intestine,and the D50%of bladder between PCECT and Pref were significant(t=-4.821,2.171,P<0.05).The comparative γ passed rates of PPCT,PCECT and Pref under the standards of 3 mm/3%and 2 mm/2%were all above 95%,and the differences were not significant(P>0.05).Conclusions:The influence of CECT on dose calculation in MRI-guided oART based on ED assignment method for rectal cancer is relatively small,which can be directly used in the design of reference plan,but the maximum dose of radiation-sensitive organs such as the small intestine should be paid attention.

Background: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. Methods: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. Results: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. Conclusion A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) is important in improving the adverse prognosis of this patient population. This study aimed to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with sepsis-associated AKI receiving CKRT. Methods: This multi-center, retrospective, observational cohort study included 1,500 patients with sepsis-associated AKI treated with intensive care and CKRT. The main predictor was a panel of 13 different systemic inflammation biomarkers. The primary outcome was 28-day mortality after CKRT initiation. Secondary outcomes included 90-day mortality after CKRT initiation, CKRT duration, kidney replacement therapy dependence at discharge, and lengths of intensive care unit (ICU) and hospital stays. Results: When added to the widely accepted Acute Physiology and Chronic Health Evaluation II score, platelet-to-albumin ratio (PAR) and neutrophil-platelet score (NPS) had the highest improvements in prognostication of 28-day mortality, where the corresponding increases in C-statistic were 0.01 (95% confidence interval [CI], 0.00–0.02) and 0.02 (95% CI, 0.01–0.03). Similar findings were observed for 90-day mortality. The 28- and 90-day mortality rates were significantly lower for the higher PAR and NPS quartiles. These associations remained significant even after adjustment for potential confounding variables in multivariable Cox proportional hazards models. Conclusion: Of the available systemic inflammation biomarkers, the addition of PAR or NPS to conventional ICU prediction models improved the prognostication of patients with sepsis-associated AKI receiving intensive care and CKRT.

This study investigated the association between serum phosphate level and mortality in acute kidney injury (AKI) patients undergoing continuous kidney replacement therapy (CKRT) and evaluated whether this association differed according to disease severity. Methods: Data from eight tertiary hospitals in Korea were retrospectively analyzed. The patients were classified into four groups (low, normal, high, and very high) based on their serum phosphate level at baseline. The association between serum phosphate level and mortality was then analyzed, with further subgroup analysis being conducted according to disease severity. Results: Among the 3,290 patients identified, 166, 955, 1,307, and 862 were in the low, normal, high, and very high phosphate groups, respectively. The 90-day mortality rate was 63.9% and was highest in the very high group (76.3%). Both the high and very high groups showed a significantly higher 90-day mortality rate than did the normal phosphate group (high: hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21–1.51, p < 0.001; very high: HR, 2.01, 95% CI, 1.78–2.27, p < 0.001). The low group also exhibited a higher 90-day mortality rate than did the normal group among those with high disease severity (HR, 1.47; 95% CI, 1.09–1.99; p = 0.01) but not among those with low disease severity. Conclusion: High serum phosphate level predicted increased mortality in AKI patients undergoing CKRT, and low phosphate level was associated with increased mortality in patients with high disease severity. Therefore, serum phosphate levels should be carefully considered in critically ill patients with AKI.

Objective To study the protective effect of Irisin in doxorubicin(Dox)induced-Cardiomyopathy and its possible mechanism.Methods AC 16 cells were used to construct Dox injury model and divided into control group(AC 16 cells were cultured with complete medium),Irisin group(AC16 cells were treated with 10 ng·L-1 Irisin for 24 h),Dox group(AC 16 cells were treated with 4 μmol·L-1 Dox for 24 h),Dox+Irisin group(AC 16 cells were pretreated with 10 ng·L-1 Irisin for 2 h,and then treated with 4 pmol·L-1 Dox for 24 h).Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)and lactate dehydrogenase(LDH)were used to detect the proliferation,apoptosis and mortality of AC 16 cells.Western blot was used to detect the expression levels of nuclear factor-κB(NF-κB)signaling pathway and apoptotic factors B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-9 protein.Mito-Tracker Red CMXRos probe was used to detect mitochondrial membrane potential.Results In the contrl group,Irisin group,Dox group,Dox+Irisin group,the rate of apoptosis were(0.97±0.09)％,0,(42.80±6.70)％,(11.74±1.79)％;the expression of Bax protein were 0.85±0.01,0.36±0.02,1.15±0.07,0.37±0.11;the expression of caspase-9 protein were 0.52±0.02,0.59±0.03,1.11±0.02,0.67±0.08;the expression of Bcl-2 protein were 1.01±0.04,1.05±0.25,0.43±0.02 and 0.99±0.30;the probability of mitochondrial damage were(0.02±0.01)％,(0.5±0.15)％,(38.6±2.39)％,(1.58±0.54)％.The difference of the above indexes between the contrl group and the Dox group were statistically significant(all P＜0.05);the difference between Dox group and Dox+Irisin group were statisically significant(all P＜0.05).Conclusion Irisin could reduce the expression level of Bax,caspase-9,p-NF-κB,and p-mTOR caused by Dox,increase the expression level of Bcl-2,ameliorate the myocardial damage caused by Dox,and reduce cardiotoxicity.

The Korean Society of Laryngology, Phoniatrics and Logopedics created a task force to establish clinical practice guidelines for the use of botulinum toxin (BT) in otolaryngology. We selected 10 disease categories: spasmodic dysphonia, essential vocal tremor, vocal fold granuloma, bilateral vocal fold paralysis, Frey’s syndrome, sialocele, sialorrhea, cricopharyngeal dysfunction, chronic sialadenitis, and first bite syndrome. To retrieve all relevant papers, we searched the CORE databases with predefined search strategies, including Medline (PubMed), Embase, the Cochrane Library, and KoreaMed. The committee reported 13 final recommendations with detailed evidence profiles. The guidelines are primarily aimed at all clinicians applying BT to the head and neck area. In addition, the guidelines aim to promote an improved understanding of the safe and effective use of BT by policymakers and counselors, as well as in patients scheduled to receive BT injections.

Objective To explore the protective mechanism of RNA binding protein LIN28 on diabetic nephropathy(DN).Methods LIN28 was overexpressed or knocked down by adenovirus in HEK 293T cells.The gene and functional signaling pathway significantly changed after overexpression of LIN28 were obtained through RNA Seq transcriptome sequencing and bioinformatics analysis.HEK 293T cells were divided into the Control group,the Treatment group,the Adv-LIN28-OE+D-ribose group and the Adv-LIN28-NC+D-ribose group in in vitro LIN28 overexpression studies.And HEK 293T cells were divided into the Control group,the Treatment group,the Adv-shRNA LIN28+D-ribose group and the Adv-shRNA NT+D-ribose group in in vitro LIN28 knockdown studies.ELISA was used to detect the levels of human advanced glycation end products(AGEs)of cells supernatants in the above groups.Western blot was used to detect the expression levels of RAGE,NF-κB and MMP-2 of cells in the above groups.Results The results of RNA-Seq transcriptome sequencing,GO analysis and KEGG analysis showed that overexpression of LIN28 resulted in a significant down-regulation of AGE-RAGE signaling pathway in HEK 293T cells(P<0.05).The results of ELISA showed that compared with the Control group,the cell in the Treatment group produced a large amount of AGEs(P<0.05);compared with the Treatment group,the AGEs level of cells in the Adv-LIN28-OE+D-ribose group was significantly decreased(P<0.05),while the AGEs level of cells in the Adv-shRNA LIN28+D-ribose group was increased(P>0.05).The results of Western blot showed that compared with the Control group,the expression levels of RAGE,NF-κB and MMP-2 of cells in the Treatment group were significantly increased(P<0.05);compared with the Treatment group,the expression levels of RAGE,NF-κB and MMP-2 of cells in the Adv-LIN28-OE+D-ribose group were significantly decreased(P<0.05),while the expression levels of RAGE,NF-κB and MMP-2 of cells in the Adv-shRNA LIN28+D-ribose group were significantly increased(P>0.05).Conclusion Overexpression of LIN28 by adenovirus at the cellular level in vitro can lead to significant differential expression of thousands of genes.In particular,it can inhibit the diabetes and complications-related AGE-RAGE signaling pathway,which is critical in the progression of DN disease,and play a role in protecting DN.

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.