ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.

Objective To evaluate the Mandarin tracking of noise tolerance(TNT)test material and compare the differences between the average tolerable noise level(aTNL)value obtained from assessment and the program-estimated tolerable noise level(eTNL).Methods A total of 25 subjects with normal hearing and aural communica-tional ability were selected to undergo two of the mandarin TNT tests successively(respectively test 1,C1;test 2,C2),and 13 of them completed the third test(C3)under the same test condition as test 2 at least 1 week later.The stimulus for the three test conditions was presented with"speech 0°,continuous noise 180°".Results The aTNL of 25 participants for C1 and C2 was 83.42±3.09 dB SPL and 83.50±3.18 dB SPL,respectively.The eTNL of 25 participants for C1 and C2 were 84.08±3.53 dB SPL and 83.95±3.85 dB SPL,respectively.The aTNL and eT-NL for 13 subjects who participated in C3 was 83.16±2.13 dB SPL and 83.18±2.64 dB SPL,respectively.The intra-session(C1 vs C2)and inter-session(C2 vs C3)test-retest reliability were 2.36 dB and 2.75 dB,respectively.Pearson correlation analysis showed that intra-session(r=0.837,P＜0.001)and inter-session(r=0.867,P＜0.001)test-retest reliability was good.There was no statistical difference between aTNL and eTNL in the other TNT tests(P＞0.05 for both)except that aTNL and eTNL were statistically different in C1(P＜0.01),and more than 90％of the subjects could obtain eTNL within 1 minute.Conclusion The test-retest reliability of Mandarin tracking of noise tolerance test is good,with advantages of high reliability and efficiency.

Attention deficit and hyperactive disorder(ADHD)is a chronic neurodevelopmental disorder characterized by inattention,hyperactivity-impulsivity,and working memory deficits.Social dysfunction is one of the major challenges faced by children with ADHD.It has been found that children with ADHD can't perform as well as typically developing children on facial expression recognition(FER)tasks.Generally,children with ADHD have some difficulties in FER,while some studies suggest that they have no significant differences in accuracy of specific emotion recognition compared with typically developing children.The neuropsychological mechanisms underlying these difficulties are as follows.First,neuroanatomically.Compared to typically developing children,children with ADHD show smaller gray matter volume and surface area in the amygdala and medial prefrontal cortex regions,as well as reduced density and volume of axons/cells in certain frontal white matter fiber tracts.Second,neurophysiologically.Children with ADHD exhibit increased slow-wave activity in their electroencephalogram,and event-related potential studies reveal abnormalities in emotional regulation and responses to angry faces when facing facial stimuli.Third,psychologically.Psychosocial stressors may influence FER abilities in children with ADHD,and sleep deprivation in ADHD children may significantly increase their recognition threshold for negative expressions such as sadness and anger.This article reviews research progress over the past three years on FER abilities of children with ADHD,analyzing the FER deficit in children with ADHD from three dimensions:neuroanatomy,neurophysiology and psychology,aiming to provide new perspectives for further research and clinical treatment of ADHD.

Liver transplantation has become an important means of treating end-stage liver diseases. However, due to various factors, liver transplant recipients are in a state of fatigue for a long time. Fatigue can lead to poor health conditions, changes in normal social functions, an increase in negative emotional states, a decrease in quality of life, and even a possible decrease in survival rate. In order to strengthen the attention of medical staff to liver transplant recipients′ fatigue, timely detection and early effective interventions, this article will review the concept, survey tools, current status, related influencing factors, and intervention measures of fatigue in liver transplant recipients, in order to provide theoretical basis for improving fatigue symptoms in liver transplant recipients.

Abstract Improving the system of adolescent myopia prevention and control and promoting adolescent healthy development is one of the main directions of healthy China construction in the new era. The paper reviewed national myopia policies and local practices, and proposed reflections on the high burden and complex etiology of myopia among adolescents, as well as unclear role and lack of coordination mandate during the COVID 19 epidemic. Based on the synergy theory, through the analysis of the functional positioning of multiple subjects in the prevention and control of myopia, the paper highlighted the multi party linkage of government, schools, medical institutions, communities, families and markets, profiling the resources and advantages of each subject, as well as dynamic management of adolescent myopia, as well as a multi subject collaborative prevention and control system with national unity, clear rights and responsibilities, and long term cooperation.

Objective:To systematically evaluate the clinical efficacy of compound α-ketoacid tablets in the treatment of diabetic kidney disease (DKD).Methods:CNKI, Wanfang database, EMBASE, PubMed and Cochrane Library database were searched for eligible records published from the establishment of individual database to November 13 th, 2022. The quality of the included studies were assessed, data were extracted, and meta-analysis was conducted using RevMan5.3. Results:A total of 26 randomized controlled trials were included, with a total of 2 790 DKD patients (1 465 in the experimental group and 1 325 in the control group). Multiple parameters were significantly improved in the experimental group compared with the control group, including 24-hour urinary protein, blood creatinine, urea nitrogen, nutritional index, oxidative stress level, fasting blood glucose, glycated hemoglobin, homocysteine, HGF, VEGF, TGF-β1, and systolic blood pressure.Conclusions:Limited low-quality evidence showed that compound α-ketoacid tablets combined with low-protein diet may be related to the improved 24-hour urinary protein, renal function, and glucose metabolism in patients with DKD. Due to the lack of randomized controlled trials designed for respective stages of DKD, the inclusion criteria of our study were relatively general, possibly leading to the lack of pertinence of the results. Some indicators showed apparent heterogeneity among different groups, and more high-quality multi-center studies with large sample sizes are still needed to verify our findings.

T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

ObjectiveTo investigate the correlation between systemic immune-inflammation index (SII) and prognosis in patients with hepatic alveolar echinococcosis. MethodsA retrospective analysis was performed for the clinical data of 242 patients who were admitted to Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, from January 2015 to December 2018 and underwent surgery for hepatic alveolar echinococcosis, and SII was calculated. The chi-square test was used for comparison of categorical data between two groups, and a Spearman correlation analysis was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of SII; the Kaplan-Meier method was used to plot survival curves and analyze overall survival time in the two groups, and the log-rank test was used for comparison of survival rates between the two groups; univariate and multivariate Cox regression analyses were used to identify the influencing factors for the prognosis of patients with hepatic alveolar echinococcosis. ResultsThe Spearman correlation analysis showed that SII was positively correlated with the postoperative fatality rate of patients with hepatic alveolar echinococcosis (r=0.267, P＜0.001). The ROC curve showed that the optimal cut-off value of SII before surgery was 758.92, and based on this, 242 patients with hepatic alveolar echinococcosis were divided into low SII (SII ≤758.92) group with 126 patients and high SII (SII ＞758.92) group with 116 patients. The low SII group had 1-, 3-, and 5-year survival rates of 98.20%, 88.47%, and 6610%, respectively, and the high SII group had 1-, 3-, and 5-year survival rates of 90.80%, 53.05%, and 27.40%, respectively. The low SII group had a cumulative survival rate of ＞50% and a mean survival time of 55.584 months (95% confidence interval［CI］: 53550-57.617), while the high SII group had a cumulative survival rate of ＜50%, a mean survival time of 39.384 months (95% CI: 35.070-43.698), and a median survival time of 43 months (95% CI: 34.694-51.306). The low SII group had a significantly better survival rate than the high SII group, and there was a significant difference in overall survival rate between the two groups (χ2=46.979, P＜005). The univariate analysis showed that SII ＞758.92 (hazard ratio ［HR］=5.907, 95% CI: 3.386-10.306, P=0.001) was an influencing factor for the overall survival time of patients with hepatic alveolar echinococcosis, and the multivariate Cox regression analysis showed that preoperative peripheral blood SII (HR=3.507, 95% CI: 1.911-6.435, P=0.001) was an independent risk factor for the overall survival rate of patients with hepatic alveolar echinococcosis. ConclusionPreoperative SII level is clearly correlated with the prognosis of patients with hepatic alveolar echinococcosis and can thus be used as a clinical indicator to evaluate the prognosis of patients. The higher the peripheral blood SII before surgery, the worse the prognosis of patients.