Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

ObjectiveTo understand the whole genome characteristics and the information for genetic evolution in the two coxsackievirus A2 (CVA2) strains isolated from patients with herpangina in Shanghai, and to provide a scientific basis for the prevention and treatment of herpetic angina. MethodsTwo CAV2 strains isolated from patients with herpetic angina in Shanghai were performed whole genome sequencing and analysis for phylogenetics, nucleotide homology, and evolution. ResultsA phylogenetic analysis of the VP1 region revealed that the two Shanghai strains both belonged to CVA2 genotype D, with the highest homology to OL357660, a strain from Yunnan. The average nucleotide identity (ANI) of the whole genome between the two Shanghai strains was 98.88%, and the ANI of the whole genome comparisons to other CVA2 genotype D strains and CVA2 genotypes A-C strains ranged from 84.64% to 97.42% and from 79.21% to 84.20%, respectively. The two Shanghai strains had low homology in the 3D region compared to the existing CVA2 strains. The phylogenetic analysis and sliding window nucleotide similarity analysis indicated that the two Shanghai strains and the Yunnan OL357660 strain might constitute a new genetic lineage. ConclusionThe two CVA2 strains isolated for the first time in Shanghai are assigned to genotype D (GenBank: PQ130039 and PQ130040), which is identical to the existing subtype prevalent in China. As represented by the Shanghai strains, a new CVA2 genetic lineage is been identified. This study has enriched the data on genetic evolution and genetic variation of CVA2 in Shanghai, indicating the requirement to strengthen surveillance for the epidemiological pattern of CVA2.

As a common neurological disease in China, stroke has an extremely high rate of death and disability, of which 80% is ischemic stroke (IS), causing a serious burden to individuals and society. Neuronal death is an important factor in the pathogenesis of stroke. Studies have shown that mitochondrial dynamics, as a key mechanism regulating intracellular energy metabolism and cell death, plays an important role in the pathogenesis of IS. In recent years, targeting mitochondrial dynamics has become an emerging therapeutic tool to improve neurological impairment after stroke. This paper reviews the research advance in recent years in IS mitochondrial dynamics, summarizing and discussing the overview of mitochondrial dynamics, the role of mitochondrial dynamics in IS, and the studies on mitochondrial dynamics-based treatment of IS. This paper helps to explore the mechanism of the role of mitochondrial dynamics in IS and effective interventions, and provides a theoretical strategy for targeting mitochondrial dynamics to treat IS in the clinic.
Humans ; Mitochondrial Dynamics/physiology* ; Ischemic Stroke/metabolism* ; Mitochondria/physiology* ; Animals ; Brain Ischemia/physiopathology* ; Energy Metabolism

The chemical composition of Paeoniae Radix Alba(PRA) is complex, with primary secondary metabolites including monoterpenoids, tannins, triterpenoids, and flavonoids. In previous studies on the material basis of PRA, it was found that, in addition to the widely studied characteristic monoterpene glycosides, tannic acid components also play an important role in the efficacy of PRA. However, their pharmacological effects have not been thoroughly investigated. This paper reviews the tannic acid components in PRA, including pentagaloyl glucose(PGG), tetragaloyl glucose(TGG), trigaloyl glucose(TriGG), and gallic acid, along with their structures, properties, and characteristics to provide a detailed discussion of their pharmacological activities and related mechanisms, aiming to offer a theoretical basis for the material basis research and clinical application of PRA.
Paeonia/chemistry* ; Tannins/chemistry* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Plant Extracts

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

Objective:To observe the changes of central visual acuity and extracentral visual acuity in eyes with non-arteritic central retinal artery occlusion (NA-CRAO).Methods:A retrospective clinical study. From January 1, 2017 to December 31, 2024, 140 patients (140 eyes) diagnosed with NA-CRAO through ophthalmic examination at Department of Ophthalmology of First People's Hospital of Xianyang City were included in the study. All affected eyes underwent best corrected visual acuity (BCVA), visual field, intraocular pressure, fundus color photography, optical coherence tomography (OCT), and fluorescein angiography (FFA) examinations. After a clear diagnosis, conservative treatment such as reducing intraocular pressure, relieving spasms, and dilating blood vessels should be given immediately. Simultaneously, intravenous and/or arterial thrombolysis therapy should be administered based on the patient's overall condition. Under the same treatment conditions as other treatments, 33 eyes were treated with hyperbaric oxygen therapy within 24 hours after seeking medical attention. The changes in central visual acuity (BCVA) and peripheral visual acuity of the affected eye one month after treatment were observed. BCVA improvement of ≥ 1 line was defined as the increase of no light sensitivity to light sensitivity or above, and the increase of light sensitivity to 0.01 or above. The visual acuity outside the center was determined by the 0 ° axis in front of the eyeball at eye level, and was 10 ° outside visual acuity on the temporal side. Multivariate analysis using logistic regression analysis.Results:Among the 140 cases (140 eyes), there were 84 males (84 eyes) and 56 females (56 eyes). The mean age was (63.89±10.78) years. The duration of illness from the onset of symptoms to the time of diagnosis was 48 (2-720) hours. 6, 1, 14, 47, 41, 16, and 15 eyes were diagnosed with BCVA without light perception, uncertain light perception, manual/anterior, digital/anterior, 0.01-0.10, and ≥ 0.10, respectively. FFA examination revealed delayed arm retinal circulation time and filling of the retinal artery trunk to the peak, with changes in the "arterial front" observed in 126 eyes. OCT examination showed extensive edema and unclear structure in the inner layer of the retina in all patients. Out of 140 eyes, 122 were treated with intravenous thrombolysis and 4 with arterial thrombolysis; 14 eyes did not receive thrombolytic therapy. After treatment, 38 eyes (27.1 %) showed an improvement of BCVA ≥ 1; 67 eyes (47.9%) did not show an improvement in BCVA, and the affected eye had a BCVA of approximately 0.6 without light perception; 17 eyes (12.1 %) showed improvement in peripheral vision, and the peripheral vision of the affected eyes ranged from 0.01 to 0.1, all of whom were patients undergoing intravenous thrombolysis, and prior to treatment, this group of patients had complete blindness in the coarse side visual field of the Amsler grid, and their out of center visual acuity could not be measured. Among the 33 eyes treated with hyperbaric oxygen therapy, 24 eyes (72.7%) showed an increase in BCVA after treatment; 9 eyes did not improve, among which 4 eyes (12.1%) showed improvement in out of center visual acuity. Among the 107 eyes that did not receive hyperbaric oxygen therapy, 49 eyes (45.8%) showed an increase in BCVA after treatment. There was no improvement in 58 eyes (54.2%), among which 13 eyes (12.1%) showed an improvement in out of center visual acuity. The results of logistic regression analysis showed that intravenous thrombolysis and hyperbaric oxygen therapy were independent predictive factors for the improvement of central and extra central visual acuity ( P<0.05). Conclusions:Hyperbaric oxygen therapy within 24 hours of seeking medical attention for patients with NA-CRAO disease course ≤ 1 month has a significant effect on the recovery of central and extra central vision. Intravenous thrombolysis and hyperbaric oxygen therapy are independent predictive factors for the improvement of central and extra central vision.

Objective To analyze the clinical characteristics and prognostic risk factors of patients with atrial fibrillation(AF)related to septic shock admitted to the intensive care unit(ICU).Methods This retrospective cohort study included 152 patients with septic shock who were admitted to the ICU between January 2020 and December 2023.Patients were categorized into AF(n=48)and non-AF(n=104)groups based on the occurrence of AF.Clinical parameters were compared between the two groups,and variables with statistically significant differences(P<0.05)were entered into a multivariate logistic regression analysis to identify clinical features associated with AF.Patients were also stratified into survival(n=103)and death(n=49)groups based on 28-day outcomes.Variables showing signifi-cant intergroup differences(P<0.05)were further included in a multivariate model to identify independent risk factors for mortality.Kaplan-Meier survival analysis was performed using AF as a binary variable,and log-rank tests were applied to compare survival curves.Results The incidence of AF was 31.58%among patients with septic shock.Compared with the non-AF group,the AF group was older,received higher cumulative doses of vasoactive agents,and had elevated levels of lactate(Lac),N-terminal brain natriuretic peptide precursor(NT-proBNP),troponin I(cTnI),tumor necrosis factorα(TNF-α),and C-reactive protein(CRP).The AF group also had higher E/e'ratios,left ventricular ejection fraction(LVEF),Acute Physiology and Chronic Health Evaluation-Ⅱ(APACHEⅡ)scores,Sequen-tial Organ Failure Assessment(SOFA)scores,and 28-day mortality rates(all P<0.05).Multivariate logistic regression identified age(odds ratio[OR]=1.060,P=0.015),SOFA score(OR=1.525,P=0.001),TNF-α(OR=1.009,P=0.026),CRP(OR=1.008,P=0.002),and E/e'(OR=1.363,P=0.023)as independent risk factors for AF.The 28-day mortality rate was 32.24%.Compared with survivors,non-survivors had significantly higher Lac,cTnI,E/e',LVEF,and TNF-α levels,higher APACHEⅡand SOFA scores,longer ICU stays,and a higher incidence of AF(all P<0.05).Multivariate analysis identified SOFA score,cTnI,E/e',and AF as independent predictors of 28-day mortality.Kaplan-Meier analysis revealed significantly poorer survival in patients with AF(χ2=6.747,P=0.009).Conclusion AF is common in ICU patients with septic shock.Advanced age,greater organ dysfunction,elevated inflammatory markers,and diastolic dysfunction are associated with AF occurrence.Organ dysfunction,myocardial injury,diastolic dysfunction,and AF are inde-pendent predictors of mortality in this population.Greater clinical attention is warranted in patients with AF and septic shock due to their elevated risk of poor outcomes.

Objective Exploring the components of complex scenarios of healthcare surges triggered by major epidemics to provide a theorical basis for building resilience in healthcare organizations.Methods A hybrid analysis method is used to summarize macro-meso-micro multi-level and multi-source heterogeneous information,extract the elements of complex scenarios of medical surge and evaluate the rationality.Fault Tree Analysis method is used to clarify the logical relationship between various scenario elements and construct scenario reasoning paths.Results 10 scenario states,11 disaster-bearing,24 emergency management and 23 scenario results are summarized and extracted to form the key elements of complex surge scenarios.Among them,M4 expansion and coordinated scheduling of key positions,B2 conventional drug inventory emergency/insufficient core treatment drugs,B emergency medical material transportation breakage,S3 disease symptom spectrum shift to severe disease,R13 prevention and control awareness laxity,and M5 media information dissemination management are the key driving factors that promote a major turning point in the scenario.The most positive scenario result is the orderly operation of the medical service system,and the most negative scenario result is the paralysis of the medical service system.Conclusion Medical institutions need to improve emergency plans based on the complex evolution scenarios of medical surges and agile governance capabilities targeting key turning points,focus on dynamically expanding and scheduling personnel in key positions,strengthen material rotation and reserve mechanisms,maintain smooth emergency logistics channels,and improve efficient management of media and public opinion,so as to comprehensively improve overall resilience.

This study was aimed at investigating the immunoregulatory function of Mycobacterium tuberculosis Rv3641c gene in modulating host type Ⅰ interferon responses.The shuttle plasmid pMV261 was used to construct Rv3641c overexpression recombinant Mycobacterium smegmatis,and the biological characteristics of the recombinant bacteria were analyzed to explore the effect of Rv3641c on the growth curve,colony morphology and stress resistance of Mycobacterium.Subsequently,RAW264.7 cells were infected with Rv3641c overexpressing Mycobacterium smegmatis,and the transcriptional expression of genes related to the inhibition of type I inter-feron pathway was determined by RT-PCR.The expression level of IFN-βprotein was determined by ELISA,and the intracellular sur-vival level was determined.As a result,the recombinant rMS::pMV261-Rv3641c was successfully constructed.The results of biologi-cal characteristics analysis showed that Rv3641c did not affect the growth of mycobacteria,but significantly changed the colony mor-phology of mycobacteria and improved its resistance to H2O2.The results of recombinant bacteria infection experiments showed that Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1β in host cells,and Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1βin host cells.The results of intracellular colonization experiments showed that the intracellular mycobacte-ria in the overexpression recombinant bacteria infection group were significantly higher than those in the empty vector group,indicat-ing that Rv3641c could promote the intracellular surviv al of mycobacteria.In summary,the Rv3641c gene of M.tuberculosis can inhibit the host type I interferon response and promote the intracellular survival of M.tuberculosis,which provides a new idea for further explor-ing the immune escape function of M.tuberculosis and the discovery of new targets for anti-tuberculosis drugs.