eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Hepato-pancreato-biliary diseases (HPBD) are often complicated. The diagnosis and treatment of HPBD involve many disciplines. The malignant degree of hepatobiliary pancreatic system is high, and the prognosis of patients is poor. The multidisciplinary team (MDT) brings specialists from different disciplines together to make a comprehensive and individualized treatment for patients. MDT is emerging in HPBD in recent years. MDT helps improve the accuracy of diagnosis and prognosis. However, there are still some controversies and obstacles in the application of MDT for patients with HPBD. We reviewed the development, current status and experience of MDT in the field of HPBD, analyze the current controversy and obstacles, and providing reference for its future application.

Lumbar spinal stenosis is a common clinical syndrome in orthopedics, frequently occurring in the elderly, and can affect the physical and mental health as well as daily life of patients. Surgery is the primary treatment measure for lumbar spinal stenosis, among which laminoplasty has received widespread attention in recent years. This article reviewed the current application status and research progress of laminoplasty for lumbar spinal stenosis in the elderly, aiming to provide reference for technical research and clinical practice in this field.

AIM: In order to bridge the gap between pharmacogenomic research and its clinical application, we propose the concept of genetic electronic identity, named "GeneFace", and developed an electronic information system which integrated "drug-gene" interactions and recommendations for personalized medicine. METHODS: Based on the self-developed Precision Medicine knowledgebase, which concludes drug directions, guidelines or important literatures with high level of evidence, we developed GeneFace with Java-based open-resource application framework Spring Boot, further developed a mobile App with cross-platform framework Uni-APP. RESULTS: The App includes six modules: genetic testing appointment, genetic knowledge introduction, individualized medication advice, medication records, Geneface interpretation, and Precision Medicine knowledgebase. By detecting the genotype of more than 300 gene loci upon first use, users import the results to form a personal "drug-gene identity card". Then scan or enter the drug name in "GeneFace", the App would automatically give corresponding medication recommendations, including: risks for possible adverse drug reactions, risks for reducing the efficacy or even ineffectiveness, and possibility for dose adjustment, etc., which increase the safety of clinical drug use. People can obtain pharmacogenomics knowledge and basic drug information in the "GeneFace" app. CONCLUSION: Development as a digital therapeutic product, the expanded application of GeneFace can rapidly promote clinical applications of basic pharmacogenomics research and significantly improve drug use safety, which creating a new model for accelerating the clinical application of personalized medicine.

[Abstract] Objective: To observe the effects of shikonin on the proliferation, apoptosis and cell cycle of human esophageal carcinoma TE-1 cells, and to explore its mechanism. Methods: TE-1 cells were treated with different concentrations of shikonin (0, 1, 5, 10 µmol/L). MTT assay was used to detect cell proliferation at different time points (24, 48 and 72 h). After treatment with shikonin for 48 h, cell apoptosis in TE-1 cells of each group was observed with Hoechst 33258 fluorescence staining. Flow cytometry was used to detect apoptosis and cell cycle. The changes in expression of TRAP1/Akt/mTOR signaling pathway related proteins were detected by Western blotting. Results: Shikonin inhibited the proliferation of TE-1 cells in a time-dose-dependent manner (P<0.05 or P<0.01). Compared with the control group, shikonin significantly promoted the apoptosis of TE-1 cells (P<0.01), induced the G0/G1 phase block of TE-1 cells (P<0.05 or P<0.01), and reduced the expression levels of TRAP1, p-Akt and p-MTOR (P<0.05 or P<0.01). The above effects were all dose-dependent. Conclusion: Shikonin can significantly inhibit the proliferation of TE-1 cells in vitro, induce G0/G1 phase arrest and promote apoptosis, which may be closely related to the inhibition of TRAP1/Akt/mTOR signaling pathway.

Objective To establish a UPLC-MS/MS method for simultaneous determination of 19 chemical drugs in Traditional Chinese Medicines and health products for treating rhinitis. Methods Separation was performed on Waters ACQU-ITY UPLC BEH-C18column(2.1 mm×100 mm,1.7 μm) with 0.1% formic acid acetonitrile solution and 0.1% formic acid aque-ous solution as the mobile phase by gradient elution.The flow rate was 0.3 mL·min-1.The column temperature was set at 35 ℃. The detection was performed by the positive ion electrospray ionization (ESI+) under multiple reactions monitoring (MRM) mode. Results The linear relationships of 19 chemical drugs were good in respective ranges with correlation coefficients higher than 0.995.The average recoveries of the low,medium,and high level were in the range of 84.9%-111.1%,and the RSDs were less than 5.2%.The limits of detection (LOD) and the limits of quantitation (LOQ) were in the range of 0.03-0.78 ng·mL-1 and 0.13-1.82 ng·mL-1,respectively. Conclusion The method is convenient,rapid,accurate,and sensitive,which can be used for the determination of chemical drugs added illegally in traditional Chinese medicines and health products for treating rhini-tis.

Objective Comparative study of gastric tube implantation at different times in patients with invasive mechanical ventilation. Methods Random sampling was used to divide 160 patients who were incubated with mechanical ventilation at the hospital into two groups,There were 80 patients in each group. Two groups of patients were routinely placed gastric tube by a stationary nurse.The observation group was treated with ordinary silica gel stomach tube at early stage(immediately)after trachea cannula, the control group still used the ordinary silica gel stomach tube after the trachea cannula late (24 hours later).The one-time successful rate,the total successful rate,the operation time and the result of the two Methods were observed in the two groups. Results The observation group Placing stomach tube one-time successful rate and the total successful rate was 75% (60/80), 97.5% (78/80), significantly higher than the control group 27.5%(22/80),72.5%(58/80),the difference was statistically significant(χ2=36.12, 19.61,P<0.01).The operation time of gastric tube in observation group was(1.49 ± 0.45)min,which was significantly lower than that of control group(3.07 ± 0.32)min,the difference was statistically significant (t=25.48,P<0.01).The observation group only heard gurgling not pumped to the gastric juice of 10 cases (12.50%), only smoke into the gastric juice does not hear the gurgling in 0 cases, both in 70 cases (87.50%),both in 0 cases,the control group were 37 cases(46.25%),0 cases,40 cases(50.00%),3 cases (3.75%). There were significant differences between the 2 groups in determining the success of gastric tube placement,and the difference was statistically significant(χ2=39.36,P<0.01). Conclusions After the trachea cannula,the ordinary silica gel gastric tube was placed in the early stage(immediately),which improved the successful rate of gastric tube placement in the mechanical ventilation patients, Shortened the operation time,improved the work efficiency and alleviated the patient's pain.

OBJECTIVE:To study the effect of natural emulsifier acacia senegal on in vivo and in vitro performance of chloro-genic acid self-microemulsion. METHODS:Chlorogenic acid self-microemulsion containing acacia senegal(new chlorogenic acid self-microemulsion)was prepared by using acacia senegal to gradually replace polysorbate 80 in chlorogenic acid self-microemul-sion containing nonionic emulsifier (traditional chlorogenic acid self-microemulsion). The appearance,morphology,particle size,conductivity,pH value,stability,in vitro release and intestinal absorption kinetics of the 2 kinds self-microemulsions were evaluated. RESULTS:50％of polysorbate 80 was replaced by acacia senegal in new chlorogenic acid self-microemulsion. The tradi-tional and new chlorogenic acid self-microemulsions had clear appearance,and approximately spherical drops. Particle sizes were (24.53 ± 3.03),(35.51 ± 5.91) nm;dectrical conductivities were (195.6 ± 0.3),(189.5 ± 0.4)μs/cm;and pH were 3.87 ± 0.02, 4.08 ± 0.03 (n=3),respectively. Compared with traditional chlorogenic acid self-microemulsion,the absorption rate constant,ef-fective permeability coefficient and absorption amount of the new one in duodenum,jejunum,ileum were increased a little (P>0.05);the above indexes in colon were obviously decreased (P<0.05). CONCLUSIONS:The new chlorogenic acid self-micro-emulsion can maintain the performance of traditional one,and increase absorption of chlorogenic acid in small intestine.

BACKGROUND:The existed artificial anal sphincter cannot sense whether there are intestinal contents in the bowel and the state of intestinal contents, and the previous studies on the intestinal content signal did not included the different parts of colon and the signals of different intestinal content status.
OBJECTIVE:To compare the differences of ultrasound signals of different intestinal content status in different parts of New Zealand rabbits detected with transmission-type ultrasonic signal detection system.
METHODS:Twenty healthy New Zealand rabbits were used;the rabbits were divided into groups according to distal part of proximal colon, distal colon and distal rectum. Five positions of solid stool particles were selected randomly as the detection point in each group. The voltage signals of stool were measured under solid, fluid, gaseous, and deflation status of the lumen.
RESULTS AND CONCLUSION:In rectum, there were no significant differences in voltage signals between solid and gaseous conditions, while there were significant differences between fluid and deflation conditions (P=0.000). Multiple comparison showed there were significant differences between four conditions in distal part of proximal colon and distal colon (P=0). There were significant differences in voltage singles between rectum, distal colon and proximal colon under solid and fluid conditions (P=0). Multiple comparison showed there were significant differences in any part of large bowel for solid and fluid status (P=0). There were no significant differences in voltage singles between rectum, distal colon and proximal colon under gaseous and deflation conditions. There was interactive effect of intestinal contents between three parts of large bowel under the four conditions (P=0.000). Transmission-type ultrasonic detection system can distinguish artificial intestinal contents sensory nerves of various intestinal contents. And the application of ultrasonic detection system to detect the intestinal contents under different conditions can provide a new effective method for the research on artificial intestinal content sensory nerves.