The present study delves into the cellular mechanisms underlying the antiviral effects of dehydrodiisoeugenol(DEH) by focusing on the transcription factor EB(TFEB)/autophagy-lysosome pathway. The cell counting kit-8(CCK-8) was utilized to assess the impact of DEH on the viability of human non-small cell lung cancer cells(A549). The inhibitory effect of DEH on the replication of influenza A virus(H1N1) was determined by real-time quantitative polymerase chain reaction(RT-qPCR). Western blot was employed to evaluate the influence of DEH on the expression level of the H1N1 virus nucleoprotein(NP). The effect of DEH on the fluorescence intensity of NP was examined by the immunofluorescence assay. A mouse model of H1N1 virus infection was established via nasal inhalation to evaluate the therapeutic efficacy of 30 mg·kg~(-1) DEH on H1N1 virus infection. RNA sequencing(RNA-seq) was performed for the transcriptional profiling of mouse embryonic fibroblasts(MEFs) in response to DEH. The fluorescent protein-tagged microtubule-associated protein 1 light chain 3(LC3) was used to assess the autophagy induced by DEH. Western blot was employed to determine the effect of DEH on the autophagy flux of LC3Ⅱ/LC3Ⅰ under viral infection conditions. Lastly, the role of TFEB expression in the inhibition of DEH against H1N1 infection was evaluated in immortalized bone marrow-derived macrophage(iBMDM), both wild-type and TFEB knockout. The results revealed that the half-maximal inhibitory concentration(IC_(50)) of DEH for A549 cells was(87.17±0.247)μmol·L~(-1), and DEH inhibited H1N1 virus replication in a dose-dependent manner in vitro. Compared with the H1N1 virus-infected mouse model, the treatment with DEH significantly improved the body weights and survival time of mice. DEH induced LC3 aggregation, and the absence of TFEB expression in iBMDM markedly limited the ability of DEH to counteract H1N1 virus replication. In conclusion, DEH exerts its inhibitory activity against H1N1 infection by activating the TFEB/autophagy-lysosome pathway.
Influenza A Virus, H1N1 Subtype/genetics* ; Animals ; Autophagy/drug effects* ; Humans ; Mice ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Influenza, Human/metabolism* ; Lysosomes/metabolism* ; Orthomyxoviridae Infections/genetics* ; Eugenol/pharmacology* ; Antiviral Agents/pharmacology* ; Virus Replication/drug effects* ; A549 Cells ; Male

The zebrafish model has attracted much attention due to its strong reproductive ability, short research cycle, and ease of maintenance. It has always been an important vertebrate model system, often used to carry out human disease research. Its motor behavior features have the advantages of being simpler, more intuitive, and quantifiable. In recent years, it has received widespread attention in the study of traditional Chinese medicine(TCM)for the treatment of sleep disorders, neurodegenerative diseases, fatigue, epilepsy, and other diseases. This paper reviews the characteristics of zebrafish motor behavior and its applications in the pharmacodynamic verification and mechanism research of TCM extracts, active ingredients, and TCM compounds, as well as in active ingredient screening and safety evaluation. The paper also analyzes its advantages and disadvantages, with the aim of improving the breadth and depth of zebrafish and its motor behavior applications in the field of TCM research.
Zebrafish/physiology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Drug Evaluation, Preclinical/methods* ; Animals ; Sleep Wake Disorders/physiopathology* ; Epilepsy/physiopathology* ; Neurodegenerative Diseases/physiopathology* ; Fatigue/physiopathology* ; Behavior, Animal/physiology* ; Motor Activity/physiology*

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Objective To analyze the effect of lumbar bone marrow composition on bone marrow diffu-sion-weighted imaging(DWI)in healthy adult women.Methods Retrospective analysis was performed on up-per abdominal MRI of 103 adult women.Bone marrow fat fraction of lumbar vertebra was measured according to two-point water-lipid separation technique,and apparent diffusion coefficient(ADC)value of lumbar verte-bra was measured according to DWI image(b=800 s/mm2).The subjects were divided into the high-signal group and the equal-low-signal group according to the signal intensity of lumbar vertebra and adjacent erector spine muscles.The effects of age,lumbar bone marrow fat fraction and menstrual status on the signal intensity and ADC value of lumbar bone marrow diffusion were analyzed.Finally,the correlation between lumbar bone marrow fat fraction and ADC value was analyzed.Results Univariate analysis showed that the lumbar bone marrow diffusion signal intensity and ADC value were affected by age,lumbar bone marrow fat fraction and menstrual status(P＜0.001).Multivariate analysis showed that age(P=0.046)and lumbar bone marrow fat fraction(P=0.005)were the influencing factors of lumbar bone marrow diffusion signal intensity,but men-strual status(P=0.242)was not the influencing factor.In addition,lumbar bone marrow fat fraction(P＜0.001)was the factor influencing the ADC value of lumbar bone marrow,and the two were negatively correla-ted(r=-0.607,P＜0.001),but age(P=0.497)and menstrual status(P=0.082)were not the influencing factors.Conclusion The bone marrow composition of lumbar vertebrae in healthy adult women has significant effects on the signal intensity and ADC value of bone marrow diffusion.

Objective:To investigate the correlation of the emm genotypes and virulence genes with the isolation sites of Group A Streptococcus (GAS). Methods:It was a retrospective study.The specimens were collected from children with impetigo in Beijing Children′s Hospital, Capital Medical University from 2006 to 2008 for GAS isolation and identification.A total of 24 GAS strains were isolated from 16 children with impetigo, among which 7 pairs of strains were isolated from the throat and skin of 7 children, and 1 pair of strains was isolated from the vulva and skin of one child, and the remaining 8 GAS strains were isolated from the skin pus samples of 8 children.Polymerase chain reaction was applied to detect the emm genotypes and 13 virulence genes ( speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa). The correlation of the emm genotypes and virulence genes with the isolation sites of GAS strains was analyzed. Results:In this study, four emm genotypes were detected, including emm1.0 (15/24), emm12.0 (4/24), emm22.0 (2/24) and emm160.0 (1/24), and one subtype emm12.19 (2/24) was detected as well.The carrying rates of 13 virulence genes speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa were 58.3%, 100%, 91.7%, 100%, 50.0%, 12.5%, 54.2%, 66.7%, 16.7%, 25.0%, 12.5%, 100% and 91.7%, respectively.All strains carried 5 to 11 virulence genes and they all carried speB, speF and smeZ.There were significant differences in the carrying rate of speA and speJ among the strains with different emm genotypes (all P<0.05). There was no significant difference in the distribution of virulence genes between skin isolates and pharyngeal isolates, including the 5 pairs of strains carrying the emm1.0 genotype (all P>0.05). Conclusions:The distribution of virulence gene of GAS in children with impetigo is significantly correlated with the emm genotype, rather than the isolation site.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To measure the distance between the lateral compression Ⅱ(LC-Ⅱ)screw guide needle and the surrounding important structures around the anterior inferior iliac spine in pelvic fractures and to locate the needle point,so as to provide anatomical reference for clinical nail placement.Methods Totally 40 adult gross specimens of embalming were implanted with LC-Ⅱ screw guide needle under the surveillance of C-arm machine,and the specimens were dissected.The shortest distance between the insertion point and the lateral femoral cutaneous nerve,femoral nerve,femoral artery,femoral vein,anterior superior iliac spine and inguinal ligament was measured.The triangle was constructed between the insertion point,anterior superior iliac spine and inguinal ligament,and the exact location of the entry point was calculated.Results The average distance between the insertion point of the male needle and the femoral vein was(50.67±7.29)mm＞the anterior superior iliac spine(43.83±7.58)mm＞the femoral artery(38.35±6.63)mm＞the femoral nerve(31.17±1.67)mm=the inguinal ligament(28.69±6.59)mm＞the lateral femoral cutaneous nerve(7.98±3.81)mm.The mean distance between the insertion point of the female needle and the anterior superior iliac spine was(45.28±7.07)mm=femoral vein(43.72±6.89)mm＞femoral artery(33.76±6.33)mm＞femoral nerve(25.66±6.46)mm=inguinal ligament(23.22±5.00)mm＞lateral femoral cutaneous nerve(8.97±4.76)mm.The projection distance of the entry point was 31.77 mm for men and 38.41 mm for women.The Angle b was 42.81°for men and 31.71° for women.Conclusion The lateral femoral cutaneous nerve is most vulnerable to injury when LC-Ⅱ screw is inserted,and the risk of injury has nothing to do with sex.The insertion point positioning method a and b made LC-Ⅱ screw placement quickly,safely and accurately,and reduced fluoroscopy time and frequency.

Objective To investigate the protective effect of dandelion flavone(DF)on lipopolysaccharide(LPS)-induced colon epithelial cell injury by intervening oxidative stress and inflammation with AT-specific binding protein 2(SATB2).Methods Colon epithelial cells FHC were cultured.FHC cells were randomly divided into control group(normal cultured),LPS group(10 μg·mL-1 LPS),experimental-L group(10 μg·mL-1 LPS+1 μmol·L-1 DF),experimental-H group(10 μg·mL-1 LPS+5 μmol·L-1 DF),experimental-H+sh-NC group(transfected with sh-NC+10 μg·mL-1 LPS+5 μmol·mL-1 DF),experimental-H+sh-SATB2 group(transfected with sh-SATB2+10 μg·mL-1 LPS+5μmol·L-1 DF).The relative expression level of SATB2 protein in FHC cells was detected by Western blotting.The survival rate of FHC cells in each group was determined by tetramethylazolium blue(MTT).The apoptosis rate of FHC cells in each group was detected by flow cytometry.The levels of malondialdehyde(MDA)and interleukin-6(IL-6)in FHC cells were detected by the kit.Results The relative expression levels of SATB2 protein in control group,LPS group,experimental-H group,experimental-H+sh-NC group and experimental-H+sh-SATB2 group were 0.83±0.09,0.19±0.03,0.66±0.05,0.62±0.07 and 0.23±0.03,respectively;cell viability rates were(100.00±1.00)％,(48.16±4.31)％,(85.31±5.83)％,(81.39±6.47)％and(58.75±5.24)％,respectively;cell apoptosis rates were(3.27±0.81)％,(41.26±2.09)％,(11.35±1.04)％,(10.29±1.26)％and(35.87±2.15)％,respectively;MDA levels were(13.16±1.73),(52.87±3.49),(23.19±2.05),(20.98±3.17)and(44.87±3.05)μmol·L-1,respectively;IL-6 levels were(507.18±103.26),(2 132.09±198.15),(883.16±136.92),(801.69±119.85)and(1 736.29±206.91)pg·mL-1,respectively.The above indicators in the LPS group showed significant differences compared to the control group(all P＜0.05);the above indicators in the experimental-H group showed significant differences compared to the LPS group(all P＜0.05);the above indicators in the experimental-H+sh-SATB2 group showed significant differences compared to the experimental-H+sh-NC group(all P＜0.05).Conclusion DF has a protective effect on LPS-induced colon epithelial cell injury by intervening oxidative stress and inflammation through SATB2.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.