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 analyze the characteristics and influencing factors of patient deaths caused by non-ionic iodine contrast media and provide recommendations for safe medication， thereby providing references for clinical application. METHODS Reports of fatal cases associated with non-ionic iodine contrast media were retrieved from databases including CNKI， Wanfang， VIP， PubMed， Cochrane Library， Web of Science， Embase， and SpringerLink. Statistical analysis was performed to examine the characteristics and influencing factors of these fatalities. RESULTS A total of 43 deaths caused by non-ionic iodine contrast media were retrieved， including 21 males （48.84%） and 22 females （51.16%）. The majority of deaths occurred in 32 patients aged 51-85 years old （74.42%）. The original diseases were mostly cardiovascular and cerebrovascular diseases （30.23%） and digestive system diseases （30.23%）， and only 2 cases had a clear allergy history （4.65%）. Among the lethal drugs， iohexol （37.21%） and iopromide （25.58%） accounted for the highest proportions. The main causes of death were anaphylactic shock （51.16%）， cardiac arrest （11.63%）， and pulmonary edema （11.63%）； 48.84% of the patients’ ADR occurred within 30 minutes， and 62.79% of the patients died on the first day. It mainly involved the circulatory system， nervous system and respiratory system， and the main manifestations were breathing difficulties， low or undetectable blood pressure， vomiting， etc. CONCLUSIONS The lethal drugs of non-ionic iodine contrast media are mainly iohexol and iopromide. The adverse reactions occur quickly. Clinically， it is necessary to focus on monitoring the vital signs within 30 minutes after medication， and timely treatment of symptoms such as dyspnea and abnormal blood pressure to reduce the risk of death.

Objective: To develop a simple digital chylous plasma device and validate its ability to accurately, standardly, and non-destructively determine chylous plasma in blood banks and clinical transfusions in hospitals. Methods: A digital chylous plasma assessment device was designed and manufactured. This device was used to measure the chylous degrees of chylous plasma samples before freezing, after freeze-thawing, before viral inactivation, and after viral inactivation. The measured chylosity index values were categorized according to the requirements specified in Appendix A of the Chinese national standard GB 18469-2001 "Quality Requirements for Whole Blood and Blood Components". This process established a digital standard for chylous plasma, enabling the identification of severe, moderate and mild chylous plasma, and non-chylous plasma. Results: The initial simple product of the digital chylous assessment device was successfully designed and manufactured. There was no significant difference in the degree of chylous plasma between pre-freezing 468.11±217.73 lux and post-thawing 538.91±273.39 lux of chylous plasma (P>0.05), or between pre-viral inactivation 858.33±387.79 lux and post-viral inactivation 928.33±166.51 lux of chylous plasma (P>0.05). The median of chylous degree values for plasma chylous index grades 0 to 6 were 45 lux, 250 lux, 620 lux, 835 lux, 1 130 lux, 1 390 lux, and 1 700 lux, respectively. The defined cutoff values/ranges for the chylous degree values corresponding to plasma chylous index grade 0 to 6 were ≤125 lux, 126-465 lux, 466-740 lux, 741-1 000 lux, 1 001-1 233 lux, 1 234-1 560 lux, and ≥1 561 lux. Conclusion: This study successfully developed the initial product of the digital chylous device and established digital standards for classifying chylous plasma. The device demonstrates the potential to meet the needs for assessment of chylous plasma in both blood banks and clinical transfusions in hospitals, thereby promoting the development and application of standardized, non-destructive chylous plasma assessment technology.

Objective: To explore the correlation between blind box consumption and non-suicidal self-injury(NSSI) among middle school students, so as to provide new theoretical insights for the prevention of NSSI. Methods: Using stratified random cluster sampling method, 2 807 middle school students aged 11-19 years old were selected from Hunan and Gansu provinces from November 2024 to March 2025. The blind box consumption questionnaire and Functional Assessment of Self mutilation Scale were administered to collect data on students blind box consumption frequency, as well as NSSI behavior. The χ 2 test was used to compare differences in the distribution of NSSI across different groups. Multivariate Logistic regression analysis was performed to infer the correlation and gender differences. Results: A total of 15.3% of middle school students reported having at least one NSSI incident in the past year, among which the reported rates of occasional NSSI (1-4 times) and repeated NSSI (≥5 times) were 5.5% and 9.8% respectively. The results of univariate analysis showed that there was statistically significant different in NSSI distribution among groups with different blind box consumption frequencies ( χ 2=55.72, P <0.05). After adjusting for confounding factors such as age, gender, school stage, family type, discipline style, pocket money, impulsiveness and emotion management, the results of multiple Logistic regression models showed that compared with the group without blind box consumption, the risks of "occasional NSSI" and "repeated NSSI" were higher in the group with blind box consumption ( OR =1.54, 1.66), and the frequency of blind box consumption(continous variable) was positively correlated with the risks of "occasional NSSI" and "repeated NSSI" among middle school students ( OR =1.26, 1.34)(all P <0.05).After gender stratification, the consumption behavior of blind boxes and the frequency of blind box consumption (continuous variable) of boys and girls were associated with "repeated NSSI"(boys: OR =1.61, 1.32, girls: OR =1.65, 1.35), and only in the male group was a correlation between blind box consumption and "occasional NSSI" observed ( OR =2.27) (all P <0.05). Conclusion Blind box consumption may be related to NSSI among middle school students, and there are gender differences in its correlation with NSSI among middle school students.

Advanced atherosclerosis is the major global cause of death, as featured by the aggregation of apoptotic cells (ACs) in necrotic cores. The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis. In this study, we constructed self-assembled procyanidins (PC) NPs for loading pitavastatin (Pita). The designed HA@PC@Pita NPs with hyaluronic acid (HA) modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC. In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages. Simultaneously, HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy, a selective autophagy of lipid droplets. In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE ^-/- mice model with advanced atherosclerosis. Taken together, this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.

Occupational noise-induced hearing loss (NIHL) is an irreversible sensorineural hearing loss that severely endangers workers’ health, making early screening crucial. This article reviewed the research progress on early screening methods for occupational NIHL, introduced the testing mechanisms of three core screening methods—tympanometry, otoacoustic emissions, and extended high-frequency audiometry —and summarized their clinical application advantages and limitations. It is proposed that multimodal combined detection (e.g., the combination of tympanometry, otoacoustic emissions, and extended high-frequency audiometry) can significantly improve the accuracy and comprehensiveness of early screening. Meanwhile, future studies with prospective cohort design are encouraged to verify the long-term monitoring value of each method and to strengthen the joint development of screening technologies with cutting-edge approaches such as machine learning, in order to further improve screening efficiency and provide stronger protection for workers’ hearing health.

ObjectiveTo develop traditional Chinese medicine （TCM） formulae for the treatment of nonsevere coronavirus disease 2019 （COVID-19） and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways， and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China， a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19， the calculation was carried out， and the artificial intelligent methods for compositing formulae， that are exhaustive method and parallel computing， were used to obtain candidate compound formulas. Finally， with reference to professional experience， an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b （Il1b）， C-X-C motif chemokine ligand 2 （Cxcl2）， C-X-C motif chemokine ligand 10 （Cxcl10）， C-C motif chemokine ligand 2 （Ccl2）， nitric oxide synthase 2 （Nos2）， and prostaglandin-endoperoxide synthase 2 （Ptgs2） using reverse transcription-quantitative polymerase chain reaction （RT-qPCR） in RAW264.7 cells treated with lipopolysaccharide （LPS）. ResultsIn macrophages and lung epithelial cells， 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome， and the result showed that Yinqiao Powder and Pingwei Powder （银翘散合平胃散， YQPWP） ranked first， reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally， YQPWP had the function of scattering wind and clearing heat， resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula， and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin （翘蒡术皮饮， QBZPY） based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells， with the reversing rates of 100%. The chief medicinal of QBZPY， including Lianqiao （Fructus Forsythiae）， Xixiancao （Herba Siegesbeckiae） and Niubangzi （Fructus Arctii）， can down-regulate multiple signaling pathways related with virus infection， immune response， and epithelial damage. RT-qPCR results indicated that compared with the model group， the QBZPY group down-regulated the mRNA expression of Il1b， tumor necrosis factor （Tnf）， Cxcl2， Cxcl10， Ccl2， Nos2 and Ptgs2 induced by LPS in RAW264.7 cells （P＜0.05 or P＜0.01）. ConclusionBased on targeted transcriptome analysis， expert experience in TCM and artificial intelligence， QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.

OBJECTIVE To provide reference for improving the rational use of antimicrobial drugs in primary township medical institutions. METHODS Based on the county prescription pre-review center， a team led by anti-infective clinical pharmacists constructed the management mode for the use of antimicrobial drugs in county-level medical communities with clinical pharmacists as the main team by finding out the main problems in the use of antimicrobial drugs in primary township medical institutions， providing feedback on the problems， organizing relevant training for the problems， improving the customization rules of the prescription pre-review software， implementing the automatic interception and pharmacist online prescription review and other measures. Data on the use of antimicrobial drugs were collected and compared in the 15 primary township medical institutions between January-June in 2022 （before the implementation of the mode） and January-June in 2023 （after the implementation of the mode）. RESULTS Compared with before the implementation of the mode， the utilization rate of antimicrobial drugs in outpatients of primary township medical institutions decreased from 24.97% before the implementation of the mode to 19.39% after the implementation of the mode； the utilization rate of antimicrobial injection in outpatients decreased from 66.10% to 46.80%； the utilization rate of intravenous drip of antimicrobial drugs in outpatients decreased from 52.33% to 40.35%； the rates of combined use of antimicrobial drugs in outpatients decreased from 12.70% to 8.19%； the reasonable rate of antimicrobial prescribing in outpatients increased from 55.28% to 73.93%. After the implementation of the mode， the proportion of antimicrobial prescriptions for each diagnosis was basically the same as before； the defined daily dose system （DDDs） and proportion of a few antimicrobial drugs changed compared with before according to the anatomical therapeutic chemical classification of drugs， among which DDDs of lincomycin， gentamicin and other drugs declined significantly； DDDs of antimicrobial drugs for each classification was basically the same as before according to AWaRe classification. CONCLUSIONS The management mode of the use of antimicrobial drugs led by anti-infective clinical pharmacists is constructed in the prescription pre-reviewing center of county-level medical communities， which can effectively improve the rational use of antimicrobial drugs in the primary township medical institutions.

Objective To summarize the application of double valve ring enlargement combined with mitral Chimney technique (Chimney Commando) in the secondary valve replacement and to analyze the efficacy in the near and medium term. Methods Patients who underwent the secondary aortic valve and mitral valve (double valve) replacement by Chimney Commando in Wuhan Asia Heart Hospital from 2019 to 2022 were included, and their clinical data were retrospectively collected to analyze the safety and feasibility of this procedure in secondary valve replacement of small aortic root patients. Results A total of 49 patients (44 females and 5 males) were included. The body surface area was 1.64±0.17 m2. The time from the first operation was 13.10±5.90 years. Except for 4 patients whose first operation was valvuloplasty, the remaining 45 patients were all patients after valve replacement, 41 patients of double valves replacement, including 39 patients with mechanical valve and 2 patients with biological valve. The majority of the aortic valves were St.Jude regent 19 mm or St.Jude regent 21 mm, accounting for 30.61% and 34.69%, respectively. The mitral valves were predominantly St.Jude 25 mm mechanical valves, making up 65.31%. All patients underwent Chimney Commando double valve ring enlargement, and the mean time of aortic occlusion was 154.00±45.40 min. The mean size of the aortic valve was 23.90±1.40 mm and that of the mitral valve was 28.20±1.20 mm, and the transvalvular pressure difference across the aortic valve was 20.16±5.76 mm Hg at 6 months postoperatively. There was one death during hospitalization due to multi-organ failure. The follow-up time ranged from 1 to 24 months with a median time of 8 months. Two patients were implanted with permanent pacemakers during the follow-up period and 1 patient died due to massive stroke and malignant arrhythmia. Conclusion Chimney Commando is safe and effective in patients with secondary double valve replacement, and the postoperative prosthetic valves have good hemodynamics, and can achieve good clinical results in the near and medium term.

Objective To acquire,evaluate and integrate the best evidence of perioperative exercise interventions in patients with liver cancer and provide evidence-based references for clinical medical staff.Methods Following the"6S"Evidence Resource Pyramid model,literatures in perioperative exercise interventions published between January 2010 and June 2022 were retrieved from various databases,including BMJ Best Practice,UpToDate,Guidelines International Network,National Guideline Clearinghouse,National Institute for Health and Clinical Excellence,Scottish Intercollegiate Guidelines Network,Medlive,Cochrane Library,JBI,Web of Science,PubMed,Embase,CINAHL,CNKI,SinoMed,Wanfang Data,American Cancer Society,American College of Sports Medicine and International Liver Cancer Association from January 2010 to June 2022.Two researchers evaluated the quality of the retrieved literatures and extracted evidences that met the inclusion criteria.Results A total of 22 articles were included,yielding 26 pieces of evidence across seven themes:the necessity of exercise,evaluation before exercise,preoperative exercise program,postoperative exercise program,exercise monitoring,health education and effect evaluation.Conclusions This study provides a summary of the best evidence regarding perioperative exercise interventions in the patients with liver cancer.The findings offer valuable references for clinical healthcare providers to deliver evidence-based care for the patients with liver cancer.