Sonogenetics is an emerging synthetic biology technique that uses sound waves to activate mechanosensitive ion channel proteins on the cell surface to regulate cell behavior and function.Due to the widespread presence of mechanically sensitive ion channel systems in cells and the advantages of non-invasion,strong penetrability,high safety and high accuracy of sonogenetics technology,it has great development potential in basic biomedical research and clinical applications,especially in neuronal regulation,tumor mechanism research,sonodynamic therapy and hearing impairment.This review discusses the basic principles of sonogenetics,the development status of sonogenetics and its application in the prevention and treatment of noise-induced hearing loss,summarizes and analyzes the current challenges and future development direction,thus providing a reference for further research and development of sonogenetics in the field of military medicine.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the relationship between the combined detection of lipoprotein-associated phospholipase A2(Lp-PLA2),protease activated receptor 2(PAR-2),and advanced oxidation protein products(AOPP)and the occurrence of in-stent restenosis after percutaneous coronary intervention(PCI),as well as its predictive value.Methods Patients with coronary heart disease after PCI were selected as the study objects.Group Ⅰ was the group without in-stent restenosis and group Ⅱ was the group with in-stent restenosis.The expressions of Lp-PLA2,PAR-2 and AOPP were detected by enzyme-linked immunosorbent assay(ELISA),and the predictive value and independent risk factors of these gene expression changes and the risk of in-stent restenosis were analyzed by receiver operating characteristic(ROC)analysis and binary logistic regression analysis.Results The blood Lp-PLA2 levels in group Ⅰ and group Ⅱ after 1 year follow-up after stenting were(190.24±33.67)and(256.14±37.68)ng·mL-1;PAR-2 levels were(1.41±0.38)and(1.95±0.43)ng·L-1,respectively;the AOPP levels were(47.25±4.62)and(58.76±4.86)μmol·L-1,respectively,and the differences were statistically significant(all P＜0.001).ROC analysis results showed that the truncation values of Lp-PLA2,PAR-2 and AOPP were 201.32 ng·mL-1,1.50 ng·mL-1 and 49.37 μmol·L-1,respectively.The area under the curve(AUC)was significantly higher than that detected alone(all P＜0.001).Binary logistic regression analysis shows that the independent risk factors for in-stent restenstenosis after PCI were Lp-PLA2 ≥ 201.32 ng·mL-1,PAR-2≥1.50 ng·L-1,AOPP ≥49.37 μmol·L-1 and LDL-C≥3.03 mmol·L-1,respectively(all P＜0.05).Conclusion The occurrence of in-stent restenosis after PCI is closely related to the increase in Lp-PLA2,PAR-2 and AOPP expression.

Objective To investigate the mechanism of apoptosis induced by acetyl-11-keto-3-boswellic acid(AKBA)in oral squamous cell carcinoma(OSCC)cells.Methods CAL27 were randomly divided into control group(conventional culture),low-dose group(40.00 μmol·L-1 AKBA),middle-dose group(80.00 μmol·L-1 AKBA),high-dose group(120.00 μmol·L-1 AKBA),3-methyladenine(3-MA)group(120.00 μmol·L-1 AKBA+2 mmol·L-1 autophagy inhibitor 3-MA).5-ethynyl-2'-deoxyuridine(Edu)assay was used to detect cell proliferation;Western blot assay was used to detect protein expression;flow cytometry was used to detect apoptosis.Mice were randomly divided into model group(construct OSCC mouse model),AKBA-L group(10.00 mg·kg-1 AKBA after modeling),AKBA-H group(20.00 mg·kg-1 AKBA after modeling),10 animals per group.After 28 days of continuous administration,weight were detected;and the expression of related proteins were detected by Western blot assay.Results The Edu positive cell rates in control group,high-dose group were(40.18±2.53)％,(12.08±0.93)％,respectively;the protein levels of autophagy associated microtubule associated protein 1 light chain 3(LC3)Ⅱ/LC3 Ⅰ in control group,high-dose group and 3-MA group were 0.33±0.05,2.93±0.39,0.56±0.07,respectively;phosphorylated adenylate activated protein kinase catalytic subunit alpha subunit 1(p-PRKAA1)protein levels were 0.34±0.04,1.03±0.07,0.99±0.09,respectively;the apoptosis rates were(4.65±0.39)％,(25.75±2.29)％,(14.92±1.49)％,respectively.The above indexes in hige-dose group were significantly different from those in the control group(all P＜0.05).The above indexes in 3-MA group were significantly different from those in high-dose group(all P＜0.05).The tumor weight of model group,AKBA-L group and AKBA-H group were(0.96±0.08),(0.55±0.06),(0.43±0.05)g,respectively;the protein levels of LC3 Ⅱ/LC3 Ⅰ were 0.47±0.09,0.94±0.21 and 1.69±0.34,respectively.The above indexes in AKBA-L group and AKBA-H group were significantly different from those in model group(all P＜0.05).Conclusion AKBA can induce cytotoxic autophagy related apoptosis and inhibit CAL27 cell proliferation,which may be related to activation of AMPK signal.

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.

Aim To investigate the effect of artificial intelligence(AI)assisting doctors with different seniority in predicting the enlargement of hematoma in the early stage of cerebral hemorrhage.Methods A total of 108 patients diagnosed with cerebral hemorrhage in Central Hospital Affiliated to Dalian University of Technology were retrospectively collected.CT images at admission and 24 hours after admission were collected.DICOM images obtained from plain CT scan were input into AI-CAD model developed by Biomind in collaboration with Temple of Heaven.A total of 9 doctors of different senior-level were selected in neurosurgery department of our hospital.Firstly,independent prediction was applied in the patients and then the study predicted whether patients would delelop hematoma enlargement within 24 hours combined with the results of auxiliary AI.The accuracy of independent prediction of doctors with different seniority and assisted AI prediction of aneurysm stability was calculated respectively.McNemar of paired samples was used to test the significance of difference between independent prediction coincidence rate and assisted AI prediction accuracy among differ-ent doctors.Results The accuracy of high,middle and low seniority doctors independently predicting the early expan-sion of cerebral hemorrhage was 58.95％,50.62％and 38.89％,respectively,and the accuracy of prediction was signifi-cantly improved after assisted AI(P＜0.001),the highest increase rate was low seniority doctors(25.92％),followed by middle seniority doctors(19.75％)and high seniority doctors(11.73％).The ability of senior physicians to independ-ently predict the expansion of intracerebral hemorrhage was strongest in patients and non-patients,with sensitivity of 18.75％(95％CI:9.44％～33.10％)and specificity of 65.94％(95％CI:59.98％～71.45％).The sensitivity of middle seniority doctors was 16.67％(95％CI:7.97％～30.76％),the specificity was 56.52％(95％CI:50.44％～62.42％),and the sensitivity of low seniority doctors was 8.33％(95％CI:2.70％～20.87％),the specificity was 44.20％(95％CI:38.29％～50.28％).However,after AI assisted the prediction of senior doctors,the sensitivity and specificity of each seniority group of doctors increased.The sensitivity of high seniority doctors was 60.42％(95％CI:45.29％～73.88％),the specificity was 72.46％(95％CI:66.72％～77.57％),the sensitivity of middle seniority doc-tors was 64.58％(95％CI:49.40％～77.45％),the specificity was 71.38％(95％CI:65.59％～76.56％),and the sensitivity of low seniority doctors was 68.75％(95％CI:53.60％～80.91％),the specificity was 64.13％(95％CI:58.13％～69.73％).Conclusion AI-CAD assisted doctors with high,middle and low seniority can improve the ac-curacy of predicting the enlargement of hematoma in early stage of cerebral hemorrhage,especially the ability of doctors with low seniority to find patients can be significantly improved,which can make up for the lack of work experience of doc-tors with low seniority to a certain extent.

Purpose::The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners.Methods::Based on the total human model for safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities were conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized.Results::There is a significant correlation observed between each criterion of skull and brain injury ( p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F-test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. Conclusion::The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.

Objective:To establish and validate reference intervals of serum vitamin K for healthy children in China.Methods:A cross-sectional study was conducted from January 2020 to May 2023, involving 807 healthy children aged 0 to 14 years, selected by stratified random sampling based on the population distribution of children in eastern, central, western, and northeastern China. Sample collection was carried out in 16 hospitals across 12 provinces, autonomous regions, and municipalities. Basic information of the children was collected using a standardized self-design questionnaire. Serum levels of vitamin K 1 and vitamin K 2 (menaquinone-4 (MK-4), menaquinone-7 (MK-7)) were measured using liquid chromatography-tandem mass spectrometry. The reference intervals was established by direct approach. The children were divided into different groups by age. Inter-group comparisons were conducted using the Kruskal-Wallis non-parametric test, and the reference intervals ( P2.5- P97.5) were determined using non-parametric methods. Screening 40 healthy children for small sample validation based on age groups within the reference range(25 from eastern, 10 from central, and 5 from western regions). Results:The age of the 807 children was 5.00 (2.00, 9.81) years, and 495 (61.3%) were males and 312 (38.7%) females. Reference intervals were established for 795 children, of whom 303 children were aged 1 month to 3 years and 492 were aged 4 to 14 years. The reference intervals for serum vitamin K 1 were 0.09-4.54 μg/L for children aged 1 month to 3 years, and 0.10-1.73 μg/L for 4-14 years. For MK-7, the intervals were 0.07-1.42 μg/L for 1 month to 3 years and 0.19-2.03 μg/L for 4-14 years. The reference intervals for MK-4 in children aged 1 month to 14 years were 0-0.42 μg/L. The measured values of serum vitamin K 1, MK-4, and MK-7 in the validation samples did not exceed the reference limit in more than 2 samples. Conclusion:Reference intervals for vitamin K 1, MK-4, and MK-7 in healthy children aged 1 month to 14 years have been established and validated, and can be used to assess vitamin K nutritional status in children.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.