Objective:To analyze the mechanism of HOX transcript anti-sense RNA(HOTAIR)promoting invasion and metastasis of gastric cancer from the perspective of its structural domains.Methods:The clinical data of 60 patients with gastric cancer were collected at the Tianjin Medical University Cancer Institute&Hospital from December 2010 to December 2012.Mutants of HOTAIR 3'and 5'domains were constructed as HOT△P and HOT△L,respectively,and the invasion and metastasis of gastric cancer cells were detected using Transwell as-say.Western blot was used to detect epithelial-mesenchymal transition(EMT)-related protein expression;RNAseq was used to analyze the differential genes between the NC and the HOT△L group.RNA was extracted from the clinical tissues for analyzing the correlation between gene expression and clinical information.Results:HOT△L promoted the invasive and metastatic ability of gastric cancer cells more visibly than HOT△P.The mechanistic studies demonstrated that HOT△L more significantly promotes the EMT process in gastric cancer cells com-pared to HOT△P.HOT△L specifically up-regulated the expression of glycine amidinotransferase(GATM).Data analysis and clinical analysis suggested that the high expression of both HOTAIR and GATM group was associated with distal metastasis in gastric cancer patients(P=0.02),which further proved that the high expression of HOTAIR and GATM predicted the poor prognosis of gastric cancer.Molecular in-vestigations suggested that GATM could promote the invasion and metastasis of gastric cancer cells by advancing the progression of EMT.Regulation of EMT by GATM is the key mechanism by which HOT△L promotes the invasive and metastatic ability of gastric cancer,as de-termined by back-complementary experiments.Conclusions:HOTAIR 5'domain regulates the EMT process through specific up-regulation of GATM,thus,promoting the invasion and metastasis of gastric cancer.

Objective:To construct a VP8-mRNA vaccine using human rotavirus spike protein VP8 domain as the immunogen and analyze its immunogenicity in mice.Methods:The VP8-mRNA sequence was designed, optimized, and synthesized. The VP8 gene of rotavirus G1P[8] type was used to construct the plasmid pUC57-VP8-Kan-SapⅠ, which was then sequenced. The plasmid confirmed by sequencing was subjected to large-scale amplification and extraction, followed by linearization, in vitro transcription, and capping. The purified capped products were encapsulated with lipid nanoparticles using a microfluidic control apparatus. The encapsulated VP8-mRNA vaccine was administered intramuscularly to mice at 10, 15, and 20 μg. Serum samples were collected for antibody detection by ELISA. Cellular immune responses were detected by flow cytometry and ELISPOT. Statistical analysis was performed using one-way or two-way analysis of variance and Tukey-Kramer test. Results:The encapsulated VP8-mRNA vaccine was rounded and spherical, with a particle size of about 100 nm, a polymer dispersion index of 0.088, and an encapsulation rate of 92.3%. Two doses of VP8-mRNA vaccine immunization could induce a good immune response in mice. The level of IgG antibody induced after immunization in the 15 μg group was comparable to that of the 20 μg group, and there was no statistical difference ( P>0.05), but the antibody levels in the two groups were significantly higher than that in the 10 μg group ( P<0.000 1). VP8-mRNA vaccine could induce neutralizing antibodies against rotavirus G1 and G9 types. The highest level of neutralizing antibodies against rotavirus type G1 was observed in the 15 μg group, which was significantly higher than that in the 10 μg group ( P<0.05). All immunization groups exhibited good neutralizing ability against rotavirus G9 type. The results of ELISPOT showed that lymphocytes from mice in each vaccine group were able to secrete IFN-γ when stimulated with VP8 peptide. Flow cytometry showed that the proportions of CD8 + T cell subsets in the vaccine groups were higher than that in the control group. Conclusion:The VP8-mRNA vaccine has good immunogenicity in mice and can induce good humoral and T-cell immune responses.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Spinal cord injury represents a severe central nervous system trauma characterized by prolonged treatment duration, limited neural regeneration, and delayed functional recovery, greatly affecting patients′ quality of life. The impaired neural tissue struggles to recover effectively due to both the hostile microenvironment and its own compromised state. Current clinical interventions, including early reduction, laminectomy decompression, and intravenous or intrathecal methylprednisolone administration, fail to simultaneously modulate the microenvironment and improve the neural status. Zinc, a trace element abundant in the central nervous system, plays a critical role in gene expression regulation, synaptic plasticity, and neuronal activity. Clinical evidences have indicated that lower serum zinc concentration in patients with spinal cord injury correlates with poorer outcomes and animal experiments have also demonstrated the neuroprotective effects of zinc. In fact, zinc supplementation therapy has not yet been developed into a mature clinical protocol. Besides, related animal studies still lack comprehensive understanding. To this end, the authors reviewed the biological characteristics of zinc, its administration routes, neuroprotective effects and mechanisms in the management of spinal cord injury, aiming to provide references for future basic research and clinical practice.

Objective:To investigate the value of Sequential Organ Failure (SOFA) score and its dynamics (ΔSOFA) in predicting mortality in hematology care unit (HCU) .Methods:A retrospective clinical study was conducted on 79 critically ill hematologic patients admitted to the Center for Critical Care Medicine, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between May and June 2024. SOFA scores and ΔSOFA were calculated within 2 days before and after HCU admission. The predictive value of SOFA and ΔSOFA in mortality was assessed using receiver operating characteristic (ROC) curve analysis.Results:Among the 79 patients, the HCU mortality rate was 54.4%. The SOFA scores on days 1–3 (D1, D2, and D3) and ΔSOFA on day 1 (ΔD_1) of all patients, leukemia patients and hematopoietic stem cell transplantation (HSCT) patients were significantly higher in the death group compared with the non-death group (all P<0.05). ROC curve analysis revealed that the D_1, D_2, D_3 scores, and ΔD_1 significantly predicted mortality ( P<0.001), with areas under the curve (AUCs) of 0.786, 0.866, 0.901, and 0.843, respectively. The sensitivity values were 74.36%, 57.89%, 62.85%, and 86.84%, while specificity values were 70%, 100%, 100%, and 67.65%, respectively. In the HSCT group, the D_-1, D_1, D_2, D_ 3, scores and ΔD_1 were predictive of HCU mortality, with AUCs of 0.833, 0.794, 0.871, 0.846, and 0.795, respectively. Sensitivity values for these scores were 100%, 85.71%, 71.43%, 57.14%, and 57.14%, while specificity values were 73.33%, 70.59%, 91.33%, 100%, and 100%, respectively. In the leukemia group, the D_1, D_2, D_3 scores, and ΔD_1 were predictive of HCU mortality, with AUCs of 0.760, 0.829, 0.846, and 0.756, respectively. Sensitivity values were 71.43%, 78.57%, 53.85%, and 71.43%, while specificity values were 76.19%, 78.95%, 100%, and 63.16%, respectively. For all patients, the D_3 score exhibited the highest specificity, while the ΔD_1 demonstrated the highest sensitivity. For patients in both the HSCT and leukemia groups, the sensitivity and specificity values of the D_1 and D_3 scores exceeded those of the ΔD_1. Conclusion:For patients with hematologic critical illness, including leukemia and those undergoing HSCT hospitalized in the HCU, D_1, D_2, D_ 3 scores and ΔD_1 are significantly associated with HCU mortality.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

Transcranial ultrasound stimulation (TUS) is a non-invasive brain stimulation technique that demonstrates great potential in treatment of neurological disorders due to its high spatial resolution and focused penetration ability, enabling millimetre-level precision modulation of specific brain regions with ultrasound to achieve neuromodulation of targeted areas. At present, numerous animal experiments and human studies have been carried out on the regulation of Alzheimer′s disease by TUS. In this review, the regulation effects of TUS on Alzheimer′s disease were introduced from the perspective of targeting different brain regions, including the hippocampus, frontal lobe and whole brain.

OBJECTIVES: To develop an early atrial fibrillation (AF) risk prediction model based on large-scale electrocardiogram (ECG) data from the Chinese population. METHODS: The data of multiple ECG records of 30 383 patients admitted in the Chinese PLA General Hospital between 2009 and 2023 were randomly divided into the training set and the internal testing set in a 7:3 ratio. The predictive factors were selected based on the training set using univariate analysis, LASSO regression, and the Boruta algorithm. Cox proportional hazards regression was used to establish the ECG model and the composite model incorporating age, gender, and ECG model score. The discrimination power, calibration, and clinical net benefits of the models were evaluated using the area under the receiver operating characteristic curve (AUROC), calibration curves, and decision curves. RESULTS: The cohort included 51.1% male patients with a median age of the patients of 51 (36, 62) years and an AF incidence of 4.5% (1370/30 383). In the ECG model, the parameters related to the P wave and QRS complex were identified as significant predictors. In the testing set, the AUROC of the ECG model for predicting 5-year AF risk was 0.77 (95% CI: 0.74-0.80), which was increased to 0.81 (95% CI: 0.78-0.83) after incorporating age and gender, with a net reclassification improvement of 0.123 and an integrated discrimination improvement of 0.04 (P<0.05). The calibration curve of the model was close to the diagonal line. Decision curve analysis showed that the clinical net benefit of the composite model was higher than that of the ECG model across the majority of threshold probability. CONCLUSIONS The composite model incorporating quantitative ECG features during sinus rhythm, along with age and gender, can effectively predict AF risk in the Chinese population, thus providing a low-cost screening tool for early AF risk assessment and management.
Humans ; Atrial Fibrillation/epidemiology* ; Electrocardiography ; Middle Aged ; Male ; Female ; China/epidemiology* ; Proportional Hazards Models ; Adult ; Risk Factors ; Risk Assessment ; East Asian People

According the Good Clinical Practice(GCP)and programmatic requirements,we analyze the management characteristics and the costs of drugs for clinical trials in different specialties from the drug management;The characteristics of the management of drugs for different specialties was summarize and the differential factors that may affect the management cost was explored,so as to provide theoretical support for the research institutions to utilize the resources in a rational and efficient way.This article provides a guarantee for the drug management with the aim of enhancing the quality and efficiency of clinical trials.