Objective To explore the targets and molecular mechanisms of salidroside in improving cognitive function at high altitudes using network pharmacology,molecular docking,and experimental validation.Methods The SwissTargetPrediction platform was used to screen for salidroside-related targets,and the GeneCards database was used to search for targets associated with high-altitude cognitive function.The VENNY 2.1 platform was used to create a Venn diagram showing the intersection of salidroside and the targets of high-altitude cognitive function.The STRING11.5 database was used to construct a protein-protein interaction network diagram to screen for the key targets.The DAVID database was used to perform the Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and a component-target-pathway network was constructed using the Cytoscape 3.7.2 software platform.Furthermore,molecular docking and experimental studies were conducted for preliminary validation.Male C57BL/6J mice were randomly assigned to three groups,a low-altitude control group(Con group)receiving sterile water via intragastric gavage,a high-altitude hypoxia group(Hyp group)receiving sterile water via intragastric gavage,and a salidroside group administered with 10 mg/kg salidroside via intragastric gavage.The Hyp group and the salidroside group were pre-treated for 3 days(once daily)before rapid ascension to an altitude of 4010 m.Then,the 2 groups were exposed to a hypoxic environment for 1 day and received an additional treatment.Hippocampal tissues were collected from all three groups,and the relevant proteins were measured by Western blot.Results A total of 100 salidroside targets,2212 high-altitude cognition-related gene targets,and 52 common targets were identified.The improvement in high-altitude cognitive function by salidroside could be closely associated with core targets such as VEGFA,GAPDH,MMP-9,HRAS,FGF-2,HSP90AA1,and MAPK1,involving mainly the PI3K-Akt,MAPK,and VEGF signaling pathways.According to the molecular docking results,GAPDH,MMP-9,and VEGFA showed the best binding ability with salidroside.Experimental findings showed that salidroside improved high-altitude cognitive function by regulating the levels of Bcl-2/Bax,SRC-1,NF-κB,Beclin-1,and LC3B Ⅱ/Ⅰ.Conclusion Salidroside exerts its therapeutic effects in improving high-altitude cognitive function by regulating the expression levels of proteins associated with cell apoptosis,cell proliferation,and cell autophagy,inhibiting inflammation and stress response,and reducing apoptosis and excessive autophagy in hippocampal neurons.

Objective To explore an individualized prediction scheme for sepsis patients with moderate to severe acute gastrointestinal injury based on clinical characteristics.Methods A retro-spective analysis was conducted on the clinical data of 316 sepsis patients admitted to Henan Tradi-tional Chinese Medicine Hospital from August 2021 to August 2024,and they were designated as ob-servation group.According to the occurrence of moderate to severe acute gastrointestinal injury during hospitalization,patients in the observation group were divided into complication group(n=165)and non-complication group(n=151).Multivariate logistic regression analysis was used to screen the in-fluencing factors for sepsis patients with moderate to severe acute gastrointestinal injury.An individu-alized nomogram prediction model was constructed,and its predictive efficacy was internally validated.Additionally,the clinical data of 158 sepsis patients admitted to our hospital from January 2020 to July 2021 were retrospectively analyzed and used as external validation group to externally validate the nomogram model.A random forest prediction model was constructed using the data from the ob-servation group,and its predictive efficacy was evaluated using the data from the external validation group.Results The results of multivariate logistic regression analysis showed that mechanical ven-tilation(OR=2.472),multiple organ dysfunction syndrome(MODS)(OR=4.023),high Se-quential Organ Failure Assessment(SOFA)score at admission(OR=3.083),high Acute Physiol-ogy and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score(OR=2.835),high white blood cell(WBC)count(OR=1.610),high blood lactate level(OR=1.893),high C-reactive protein(CRP)level(OR=2.036),high D-lactate level(OR=2.620),high endotoxin level(OR=3.834),high diamine oxidase(DAO)level(OR=3.916),high intestinal fatty acid-binding pro-tein(I-FABP)level(OR=4.175),and high intra-abdominal pressure(OR=3.511)were all risk factors for sepsis with moderate to severe acute gastrointestinal injury(P＜0.05).High levels of glucagon-like peptide-2(GLP-2)(OR=0.825),high gastric motility index(MI)(OR=0.485),and high superior mesenteric artery end-diastolic velocity(VPd)(OR=0.559)at admis-sion were all protective factors(P＜0.05).Based on the above factors,a nomogram prediction model for sepsis with moderate to severe acute gastrointestinal injury was constructed.After internal and external validation,the concordance indices were 0.862 and 0.858,respectively,and the cali-bration curves closely fitted the ideal curves.The receiver operating characteristic(ROC)curve showed thatthe sensitivity,specificity,and area under the curve(AUC)of the model's predictions were 88.48％,86.09％,0.889 and 87.50％,85.90％,0.884,respectively.The decision analy-sis curve showed that the model had a high net benefit when the threshold probability was in the ran-ges of 0.25-0.94 and 0.31-0.98.According to the ranking based on the average decrease in Gi-ni index in the random forest prediction model,MODS,SOFA score,I-FABP,DAO,and endotoxin were the top five indicators,which had a significant impact on the prediction of moderate to severe acute gastrointestinal injury.The ROC curve assessment showed that the sensitivity,specificity,and AUC of the random forest prediction model were 78.75％,83.33％,and 0.816,respectively.The sensitivity and AUC of the individualized nomogram model for predicting sepsis with moderate to se-vere acute gastrointestinal injury were higher than those of the random forest prediction model,and their specificities were basically equivalent.Conclusion Mechanical ventilation,MODS,and SOFA score,APACHE Ⅱ score,WBC count,blood lactate,CRP,GLP-2,D-lactate,endotoxin,DAO,I-FABP,intra-abdominal pressure,MI,and VPd at admission are all influencing factors for sepsis with moderate to severe acute gastrointestinal injury.The constructed individualized nomo-gram prediction model has important guiding value for guiding the early clinical screening of high-risk patients and the timely formulation of appropriate intervention plans.

Preschool age(3-6 years old)is a critical period for visual development, and it is crucial to detect and treat visual problems in preschool children as early as possible. Visual acuity charts are important tools for screening visual issues in children. In China, the commonly used charts are the standard logarithmic visual acuity chart and the pediatric optotype chart, while overseas, the Lea, HOTV, and ETDRS visual acuity charts are frequently employed. Numerous studies have reported the measurability, repeatability, and sensitivity of these three charts in diagnosing visual-related problems in children. However, the application of these three charts is relatively limited in China. This article provides a comprehensive review of the design principles, clinical applications, and characteristics of these three visual acuity charts, so as to better understand their applicability and limitations in preschool children, and provide reference for the selection and improvement of vision examination methods in the future.

To analyze the differences in cerebral blood flow (CBF) characteristics among children with different subtypes of attention deficit and hyperactivity disorder (ADHD) and their relationship with executive function using arterial spin labeling (ASL) technology.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To understand the genome analysis and molecular typing of foodborne Yersinia enterocolitica ( Y.e) strains in Liaocheng City of Shandong Province from 2020 to 2021. Methods:The Y.e strains were isolated from raw meat and meat products. Then we made the strain identification, drug sensitivity test, virulence gene test, pulsed-field gel electrophoresis (PFGE), and whole genome sequencing (WGS). The genome sequencing data were assembled with the microbial genome annotation package. We performed the multilocus sequence typing (MLST) and core genome multilocus sequence typing (cgMLST) and used WGS-based single nucleotide polymorphism typing (wg-SNPs) method to carry out genetic evolution analysis with 14 domestic and Y.e genomes obtained from the NCBI. Results:A total of 21 strains of Y.e were detected from 165 samples, with a detection rate of 12.73%. The 20 strains of Y.e were sequenced successfully. The 20 strains of Y.e carries a variety of drug resistance genes and virulence genes, showing multiple drug resistance. The virulence gene PCR test showed that 21 strains of Y.e having two virulence genes. Cluster analysis of PFGE, MLST, and cgMLST showed that the genomics of 21 strains was highly diverse. The genetic evolution analysis of wg-SNPs showed that 20 Y.e strains could be divided into two main evolutionary branches. Conclusions:Y.e strains isolated from raw meat in Liaocheng City carry a variety of drug resistance genes and virulence genes, and the molecular typing is highly diverse, which may cause infection risk. The molecular biological monitoring of Y.e in raw meat should be strengthened, and genome sequencing and molecular typing detection be carried out to provide the theoretical basis for foodborne illness caused by Y.e.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Background: There is an urgent need to find reliable and rapid bovine tuberculosis (bTB) diagnostics in response to the rising prevalence of bTB worldwide. Toll-like receptor 2 (TLR2) recognizes components of bTB and initiates antigen-presenting cells to mediate humoral immunity. Evaluating the affinity of antigens with TLR2 can form the basis of a new method for the diagnosis of bTB based on humoral immunity. Objectives: To develop a reliable and rapid strategy to improve diagnostic tools for bTB. Methods: In this study, we expressed and purified the sixteen bTB-specific recombinant proteins in Escherichia coli. The two antigenic proteins, MPT70 and MPT83, which were most valuable for serological diagnosis of bTB were screened. Molecular docking technology was used to analyze the affinity of MPT70, MPT83, dominant epitope peptide of MPT70 (M1), and dominant epitope peptide MPT83 (M2) with TLR2, combined with the detection results of enzyme-linked immunosorbent assay to evaluate the molecular docking effect. Results: The results showed that interaction surface Cα-atom root mean square deviation of proteins (M1, M2, MPT70, MPT83)-TLR2 protein are less than 2.5 A, showing a high affinity.It is verified by clinical serum samples that MPT70, MPT83, MPT70-MPT83 showed good diagnostic potential for the detection of anti-bTB IgG and M1, M2 can replace the whole protein as the detection antigen. Conclusions Molecular docking to evaluate the affinity of bTB protein and TLR2 combined with ELISA provides new insights for the diagnosis of bTB.

A young female patient presented with fever, arthralgia, and rash was diagnosed with adults still's disease. When treated with glucocorticoid steroid, the above patient progressed to anuria, sudden, and confusion. After a teamwork involving different departments, the patient was finally diagnosed with atypical hemolytic uremic syndrome (aHUS) and treated with good outcome. aHUS is a rare disease, while Eculizumab is an orphan drug. The diagnosis and treatment of the patient reveals the importance of multidisciplinary team on the diagnosis and treatment of rare and difficult diseases.

Objective:To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients.Methods:A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results:The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively ( P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions:Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.