Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVES: This study aimed to investigate the association between temporomandibular disorder (TMD) and insomnia using a two-sample Mendelian randomization (MR) approach. METHODS: Bidirectional MR analyses of two samples, TMD (n=377 277) and insomnia (n=375 359), were performed using genome-wide association study statistics published in the FinnGen database. Instrumental variables were first screened, and then inverse variance weighting (IVW) and MR-Egger were used as the main-effect assessment methods. Weighted median, weighted mode, and simple mode served as supplementary methods. We used IVW and MR-Egger to test for heterogeneity, as well as MR-Egger intercepts to assess the single nucleotide polymorphism (SNP) potential level of multiplicity effects. Sensitivity analyses were conducted based on leave-one-out to identify potentially influential SNPs. All analyses were conducted by using the two-sample MR R package and were considered statistically significant when P<0.05. RESULTS: MR analysis showed the presence of TMD on insomnia (OR=1.089, 95%CI: 1.017-1.166, P=0.014). Meanwhile, no effect of insomnia on TMD (OR=0.996, 95%CI: 0.964-1.029, P=0.816) was found. The sensitivity-analysis showed that no heterogeneity existed (P>0.05), and the presence of horizontal pleiotropy was not detected (P>0.05). Leave-one-out sensitivity analysis showed no single SNP, which may affect the causal relation. All findings indicated that the causal relationship between TMD and insomnia was not significantly affected by any individual SNP and that IV did not bias the results. CONCLUSIONS Results of MR analyses showed that TMD is a risk factor for insomnia, whereas insomnia is not a risk factor for TMD.
Humans ; Sleep Initiation and Maintenance Disorders/genetics* ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Temporomandibular Joint Disorders/complications* ; Genome-Wide Association Study

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To explore the challenges faced by online appointment nurses during nasogastric intubation and to provide a reference for improvement of the quality and safety of the services provided by online appointment nursing.Methods A purposive sampling was employed to select 13 online appointment nurses from our hospital who had previously provided home nasogastric intubation services for patients.Semi-structured interviews were conducted with the online appointment nurses.The results acquired from the interviews were analysed using Colaizzi's method.Results Two themes were identified.Theme 1 covered the increased risks of nasogastric intubation due to the patients themselves and home environment,which included 4 sub-themes of difficulties in identification and response due to complex conditions of patient,high risk of a sudden asphyxia with poor resuscitation facility,psychological stress from unfamiliar home environment,and more challenges in risk identification due to limited conditions for performing home-based intubation procedures;Theme 2 covered the coping strategies of online-scheduled nurses,which included the improvement of knowledge and skills in emergency nursing to improve comfidence and judge ability of intubation,the strengthening of nurse-patient communication to build a trust and cooperation,the conduct of thorough assessment to ensure procedural safety,and the use of alternative tools and collaboration with family members.Conclusion Online appointment nurses face challenges and risks from both of the procedures and patients themselves during home based nasogastric intubation.Hospitals and relevant management should actively implement corresponding strategies,provide training and guidance for online appointment nurses,develop relevant regulations,and improve the management mechanisms of the internet platform to ensure the safety of home based nasogastric intubation for online appointment nurses and improve the quality of the"Internet Plus Nursing Services."

Yang being solid is an important summary of the normal functional state of yang qi in The Yellow Emperor's Inner Classic.Based on the theory of yang being solid and able to hold on,it is proposed that yang being solid is essential to maintain the state of tightness,thoroughness and quietness for maintaining the health of the human body.Yang losing its solidity is the core patho-genesis of the onset and progression of malignant tumors,which manifests as yang deficiency,yang depression and yang restlessness.If yang is not solid due to its deficiency,yang will lose its warmth and defense and the evil qi will be retained;if yang is not solid due to its depression,yang will lose its warmth and circulation and phlegm and stasis will gather;if yang is not solid due to its restlessness,yang will lose its tranquility,burn yin and consume essence.Aiming at the core pathogenesis of yang losing its solidity,the treatment methods of warming yang and replenishing qi to treat the disease before it occurs,unblocking yang and removing turbidity to disperse the staleness,and clearing and resolving restless yang to fight cancer and detoxify are used in clinical practice.Restoring the solidity of yang is taken as the goal of treating malignant tumors,which provides ideas for the clinical practice of treating malignant tumors with traditional Chinese medicine.

Objective:To explore the correlation between skeletal muscle mass and strength with metabolic syndrome in children.Methods:This cross-sectional study was conducted involving 383 children aged 10 to 15 years who visited the Department of Child Health Care, Children′s Hospital of Nanjing Medical University from June 2021 to December 2022. Their height, weight, waist circumference, body composition, grip strength and blood pressure were measured. Relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index were calculated. The levels of fasting blood glucose, lipids and insulin were tested. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Children were divided into the metabolic syndrome group and the non-metabolic syndrome group. Independent t test or Mann-Whitney U test etc. was used to compare the difference between groups. Spearman correlation analysis and binary Logistic regression were used to investigate the correlation between skeletal muscle mass and strength and metabolic syndrome. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to compare the accuracy of the index of skeletal muscle in predicting metabolic syndrome in children. Results:Among the 383 children, 282 (73.6%) were male, at the age of 11.4 (10.6, 12.5) years. There were 216 children (56.4%) diagnosed with obesity and 90 children (23.5%) diagnosed with metabolic syndrome. Relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index of the metabolic syndrome group were all lower than those in the non-metabolic syndrome group (all P<0.001). After adjusting for sex and age, relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index were all negatively correlated with body mass index ( r=-0.84, -0.38, -0.63), waist circumference ( r=-0.76, -0.36, -0.70), systolic blood pressure ( r=-0.42, -0.21, -0.38), diastolic blood pressure ( r=-0.33, -0.18, -0.24), triglycerides ( r=-0.29, -0.13, -0.23), fasting insulin ( r=-0.28, -0.20, -0.29), and HOMA-IR ( r=-0.26, -0.18, -0.26) (all P<0.05), and positively correlated with high-density lipoprotein cholesterol ( r=0.38, 0.13, 0.31, all P<0.01). After adjusting for sex and age, high relative skeletal muscle mass, high muscle-to-fat ratio, and high grip strength-to-body weight index all decreased the risks of metabolic syndrome ( OR=0.80, 0.55, 0.90), obesity ( OR=0.53, 0.64, 0.82), hypertension ( OR=0.86, 0.58, 0.92), low high-density lipoprotein cholesterol ( OR=0.83, 0.62, 0.92), hypertriglyceridemia ( OR=0.88, 0.78, 0.96). After adjusting for sex and age, high relative skeletal muscle mass and high grip strength-to-body weight index all decreased the risks of hyperglycemia ( OR=0.93 and 0.95, all P<0.05). ROC curve analysis showed that the relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index all had good predictive accuracy of metabolic syndrome in children (AUC=0.79, 0.71, 0.76), with optimal cutoff values of 40%, 1.2, and 35%, respectively. Conclusions:High relative skeletal muscle mass, high muscle-to-fat ratio, and high grip strength-to-body weight index are all protective factors for metabolic syndrome in children. Regular measurement of skeletal muscle mass and grip strength can aid in the early identification and prevention of obesity and metabolic syndrome during childhood .

Objective:To evaluate the relationship between superoxide dismutase 2 (SOD2) lactylation and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy-ferroptosis during cerebral ischemia-reperfusion (IR) in mice.Methods:Thirty-six clean-grade male C57BL/6 mice, aged 8-10 weeks, weighing 22-25 g, were divided into 4 groups ( n=9 each) using a table of random numbers: sham operation group (Sham group), cerebral IR group (IR group), IR+ glycolysis inhibitor 2-DG group (IR+ 2-DG group), and IR+ 2-DG+ NCOA4 overexpression group (IR+ 2-DG+ LvNCOA4 group). The model of cerebral IR injury was established by occlusion of the middle cerebral artery for 1 h followed by 24 h of reperfusion using the intraluminal suture method in anesthetized animals. 2-DG 250 mg/kg was intraperitoneally injected at 90 min before ischemia in IR+ 2-DG and IR+ 2-DG+ LvNCOA4 groups. The lentivirus overexpressing NCOA4 2 μl was injected into the ventricles at 7 days before ischemia in IR+ 2-DG+ LvNCOA4 group. The percentage of cerebral infarct volume was determined, the viable neurons were counted, and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) were measured by enzyme-linked immunosorbent assay. The expression of SOD2, lysine 114 lactylation of superoxide dismutase 2 (SOD2-K114la), NCOA4, microtubule-associated protein 1 light chain 3β (LC3B), and acyl-CoA synthetase long-chain family member 4 (ACSL4) was determined by Western blot. Mitochondrial morphology was examined by electron microscopy. Results:Compared with Sham group, the percentage of cerebral infarct volume was significantly increased, the number of viable neurons was decreased, the levels of ROS and MDA were elevated, the content of GSH was reduced, the expression of SOD2-K114la, NCOA4, LC3B and ACSL4 was up-regulated, the expression of SOD2 was down-regulated ( P<0.05), and the mitochondrial injury was aggravated in IR group. Compared with IR group, the percentage of cerebral infarct volume was significantly decreased, the number of viable neurons was increased, the mitochondrial injury was alleviated, the levels of ROS and MDA were decreased, the content of GSH was increased, the expression of SOD2-K114la, NCOA4 and ACSL4 was down-regulated, and the expression of SOD2 and LC3B was up-regulated in IR+ 2-DG group ( P<0.05). Compared with IR+ 2-DG group, the percentage of cerebral infarct volume was significantly increased, the number of viable neurons was decreased, the levels of ROS and MDA were elevated, the content of GSH was reduced, and the expression of NCOA4, LC3B and ACSL4 was up-regulated ( P<0.05), no significant change was found in the expression of SOD2 and SOD2-K114la ( P>0.05), and the mitochondrial injury was aggravated in IR+ 2-DG+ LvNCOA4 group. Conclusions:SOD2 lactylation promotes NCOA4-mediated ferritinophagy-ferroptosis by enhancing oxidative stress, thereby contributing to the cerebral IR injury in mice.

Objective:Using bacterial culture as the gold standard, to evaluate the agreement of rapid antigen detection test (RADT) and rapid nucleic acid test (RNAT) in diagnosing group A Streptococcus (GAS) pharyngitis in pediatric outpatients, and assess their potential clinical utility. Methods:This cross-sectional study prospectively collected throat swab specimens and clinical data of 338 children diagnosed with acute pharyngitis at the Department of Outpatient Beijing Children′s Hospital, Capital Medical University, between July 2023 and February 2024. The specimens were tested for GAS bacterial culture, RADT and RNAT. Using bacterial culture results as the reference standard, Kappa consistency analysis was performed to assess the diagnostic concordance between RADT and RNAT. Chi-square test was used to compare clinical characteristics between cases diagnosed by different methods.Results:In the 338 children diagnosed with pharyngitis, 195 were male and 143 were female, with an age at the visit of 7.4 (5.9, 7.4) years. The positivive rates for GAS detection were 25.7% (87/338) by bacterial culture, 20.7% (70/338) by RADT, and 41.7% (141/338) by RNAT. In terms of diagnostic performance, RADT exhibited a higher specificity (96.8% (243/251)) and better agreement with bacterial culture results ( κ=0.73), whereas RNAT showed greater sensitivity (95.4% (83/87)) but lower specificity (76.9% (193/251)) and moderate agreement ( κ=0.61). Among the 87 children with positive bacterial culture for GAS, 56 were male and 31 were female, with an age at visit of 7.3 (6.2, 8.8) years. Clinically, body temperature predominantly ranged from 38.1 to 39.0 ℃ in 48 cases (55.2%), and common accompanying symptoms included sore throat 62 cases (71.3%), cough 33 cases (37.9%), and cervical lymphadenopathy or tenderness 16 cases (18.4%). On physical examination, tonsillar enlargement was present in 73 cases (83.9%) and exudate in 37 cases (42.5%). The McIsaac score was most frequently 4 points, observed in 37 cases (42.5%). Laboratory tests showed a peripheral white blood cell (WBC) count of 14.5 (12.3, 18.7)×10?/L and C-reactive protein (CRP) concentration of 22.0 (10.1, 41.4) mg/L. There were no statistically significant differences in the proportion of fever, sore throat, cough, tender cervical lymphadenopathy, tonsillar exudates, or tonsillar enlargement, nor in WBC count or CRP, among children who tested positive by RADT, RNAT, or bacterial culture (all P>0.05). Conclusions:Compared with bacterial culture,the RADT demonstrates higher specificity, while the RNAT exhibits greater sensitivity. Both methods show good concordance with culture results and may serve as effective adjunctive tools for the early screening of GAS pharyngitis.

Objective To develop an erythrocyte-based delivery system for butyrylcholinesterase(BChE)that is capable of prophylaxis against organophosphorus nerve agents.Methods Recombinant BChE was produced and analyzed for oligomerization via polyacrylamide gel electrophoresis(PAGE)and Western blotting.A modified hypotonic preswelling method was employed to prepare BChE-loaded erythrocytes.The drug loading capacity and encapsulation efficiency were quantified using enzyme-linked immunosorbent assay(ELISA).Catalytic activity was assessed in vitro with an activity detection kit.The system was characterized via scanning electron microscopy(SEM),flow cytometry and a hematology analyzer.Results Recombinant BChE predominantly existed as dimers(85％dimer,15％monomer).The optimized volume ratio of erythrocytes to hypotonic solution was determined as 1:7.Compared with native and empty erythrocytes,BChE-loaded erythrocytes exhibited significantly higher catalytic activity(P＜0.001).The mean corpuscular volume of BChE-loaded erythrocytes increased(P＜0.001),while the mean content of corpuscular hemoglobin and hemoglobin in erythrocytes per 100 mL decreased(P＜0.001).SEM revealed no morphological differences(biconcave disc shape).Hypotonic preswelling moderately increased erythrocyte apoptosis(P＜0.001),but no statistical difference was observed between BChE-loaded and hypotonic-treated erythrocytes(P＞0.05).CD47 expression remained unchanged compared to native erythrocytes(P＞0.05).Conclusion The modified hypotonic preswelling method can generate BChE-loaded erythrocytes that retain the characteristics of native erythrocytes while conferring catalytic activity,offering a novel strategy for clinical intervention against organophosphorus poisoning.

Objective To heterologously express and purify the small ubiquitin-like modifier(SUMO)tag fused organo-phosphorus hydrolase mutant H257Y/L303T(YT),namely SUMO-YT,and evaluate its hydrolytic capacity against ethyl paraoxon and soman.Methods The SUMO tag encoding gene was constructed at the N-terminus of the YT encoding gene with a linker sequence via enzyme digestion and ligation before SUMO-YT was expressed in Escherichia coli.SUMO-YT and YT were purified through ammonium sulfate precipitation and affinity chromatography to obtain high-purity target proteins.The activity and kinetic parameters of the recombinant enzymes were examined using ethyl paraoxon and soman as substrates.Results The system for expression and purification of recombinant enzymes was established,yielding SUMO-YT and YT,and the former exhibited more significantly enhanced hydrolytic efficiency than the latter,with catalytic rates 11-fold higher for paraoxon and 4.4-fold higher for soman.At 37 ℃ and pH 7.2,SUMO-YT reduced the inhibition rate of acetylcholinesterase(AChE)by soman from 100％to 45.7％within 3 minutes,whereas YT reduced it to no more than 80％.Conclusion The high-activity recombinant SUMO-YT is prepared.SUMO tag fusion can significantly enhance the hydrolytic capacity of YT against ethyl paraoxon and soman.