ObjectiveTo investigate the cardioprotective effects of ginsenoside Rg₂ in regulating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway following acute myocardial infarction （AMI） in rats. Methods（1） Cellular experiment： Cardiomyocytes were isolated from 24-hour-old Sprague-Dawley （SD） neonatal rats and subjected to primary culture. An in vitro model of cardiomyocytes under an ischemic-hypoxic microenvironment was established. Cardiomyocytes were pretreated with ginsenoside Rg₂ （1， 2， 3 mg·L^-1） for 4 hours， then placed in RPMI 1640 serum-free medium and cultured for 24 hours in a three-gas incubator （94% N₂， 5% CO₂， 1% O₂）. The survival rate of cardiomyocytes was assessed using the methyl thiazolyl terazolium （MTT） assay. The levels of lactate dehydrogenase （LDH） leakage， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） activity， and malondialdehyde （MDA） content in the cell culture supernatant were measured using spectrophotometry. （2） Animal experiment： Specific-pathogen-free （SPF） SD rats were used to establish an AMI model using the Olivette method combined with previous studies. Rats that survived 24 hours post-surgery were randomly divided into a model group and ginsenoside Rg₂ high-， medium-， and low-dose groups. The normal and model groups received normal saline， while the ginsenoside Rg₂ groups were administered intragastrically at doses of 8， 4， and 2 mg·kg^-1， once daily for 3 days. The levels of SOD， MDA， and GSH-Px in myocardial tissues were detected. Cardiomyocyte apoptosis was assessed using the TdT-mediated dUTP biotin nick end labeling （TUNEL） assay. The mRNA and protein expression levels of PI3K， Akt， mTOR， p62， nuclear factor-κB p65 （NF-κB p65）， and microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ in myocardial tissues were analyzed using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. Pathological changes in the infarct border zone were observed under a light microscope. Results（1） Cellular experiment： Compared with the normal group， the model group exhibited a significantly decreased cardiomyocyte survival rate， as well as reduced SOD and GSH-Px activity， whereas LDH activity and MDA content were significantly increased （P<0.05）. Compared with the model group， ginsenoside Rg₂ intervention significantly increased cardiomyocyte survival， SOD activity， and GSH-Px activity， while reducing LDH activity and MDA content （P<0.05） in a dose-dependent manner. Pathological examination revealed that ginsenoside Rg₂ alleviated infarct size， myocardial degeneration， and necrosis， while significantly reducing cardiomyocyte apoptosis. （2） Animal experiment： Compared with the normal group， the model group exhibited significantly lower SOD and GSH-Px activity （P<0.05） and higher MDA content （P<0.05） in myocardial tissues. Compared with the model group， all ginsenoside Rg₂ groups showed significantly increased SOD and GSH-Px activity （P<0.05） and reduced MDA content （P<0.05）. Compared with the normal group， the model group exhibited significantly decreased mRNA and protein expression levels of PI3K， Akt， mTOR， p62，and LC3 Ⅱ/Ⅰ，whereas the expression levels of NF-κB p65 were significantly increased （P<0.05）. Compared with the model group， the ginsenoside Rg₂ groups showed significantly increased PI3K， Akt， mTOR， and p62 expression， while NF-κB p65 expression levels were significantly decreased （P<0.05） in a dose-dependent manner，the mRNA and protein expression levels of LC3 Ⅱ/Ⅰ in ginsenoside Rg₂ high-dose groups were significantly increased（P<0.05）. ConclusionGinsenoside Rg₂ exerts cardioprotective effects following AMI in rats， potentially through the regulation of PI3K/Akt/mTOR-related protein expression.

Diffuse large B-cell lymphoma （DLBCL） is a highly heterogeneous disease. Although standard first-line regimens can cure ＞50% of patients， approximately one-third of them develop relapsed/refractory DLBCL （r/r DLBCL）. Consequently， immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL. The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment， antibody-based therapies have evolved rapidly， progressing from monoclonal antibodies （e.g.， rituximab， tafasitamab） to bispecific antibodies（e.g.， odronextamab，glofitamab， epcoritamab） and antibody-drug conjugate （e.g.， polatuzumab vedotin， loncastuximab tesirine）. These engineered agents enhance immune cytotoxicity and tumor-specific targeting， providing novel therapeutic options for r/r DLBCL patients.

OBJECTIVE: To observe the effect of electroacupuncture combined with enhanced recovery after surgery (ERAS) protocol on promoting intestinal function in patients after gastric cancer surgery. METHODS: Forty-four patients who underwent radical gastrectomy for gastric cancer were randomly divided into an experimental group (22 cases, 3 cases were excluded) and a control group (22 cases, 4 cases were excluded). Both groups received treatment under ERAS protocol, the experimental group was given electroacupuncture at bilateral Neiguan (PC6), Hegu (LI4), Zusanli (ST36) and Quchi (LI11), disperse-dense wave was selected, with frequency of 2 Hz/100 Hz. The control group received placebo electroacupuncture intervention, with the same acupoints as the experimental group, electrode pads were placed on the acupoints without electrical stimulation. Each session lasted 30 min, starting from 1 h after surgery, once every 24 h, until the patient resumed anal flatus. The intestinal sound rate of both groups was observed 24 h before surgery and 24, 48 h after surgery. The bowel sound recovery time (BSRT), time to first anal flatus, time to first defecation, and tolerance to oral enteral nutrition suspension were compared between the two groups. The levels of serum C-reactive protein (CRP), interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured 24 h before surgery and 24 h after surgery in both groups. RESULTS: The intestinal sound rate 24 h after surgery was decreased compared with that 24 h before surgery in the two groups (P<0.05), the intestinal sound rate 24, 48 h after surgery in the experimental group was higher than that in the control group (P<0.05). The BSRT in the experimental group was earlier than that in the control group (P<0.05) .The levels of serum CRP, IL-6, IL-10 24 h after surgery in the experimental group were higher than those 24 h before surgery (P<0.05), while the levels of serum CRP, IL-4, IL-6, IL-10, IFN-γ in the control group were higher than those 24 h before surgery (P<0.05); the levels of serum CRP、IL-4、IFN-γ 24 h after surgery in the experimental group were lower than those in the control group (P<0.05) .The tolerance rate of oral enteral nutrition suspension in the experimental group was 84.2% (16/19), which was higher than 50.0% (9/18) in the control group (P<0.05). CONCLUSION Electroacupuncture combined with ERAS protocol can improve the intestinal motility, shorten the BSRT, enhance the tolerance of oral intake, and reduce inflammatory response in patients after gastric cancer surgery.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Acupuncture Points ; C-Reactive Protein/metabolism* ; Electroacupuncture ; Gastrectomy ; Interleukin-10 ; Interleukin-6 ; Intestines/physiopathology* ; Stomach Neoplasms/therapy*

Objective To explore the prognostic value of glycolysis-related genes in colorectal cancer (CRC) patients and formulate a novel glycolysis-related prognostic risk model. Methods Single-cell and bulk transcriptomic data of CRC patients, along with clinical information, were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Glycolysis scores for each sample were calculated using single-sample Gene Set Enrichment Analysis (ssGSEA). Kaplan-Meier survival curves were generated to analyze the relationship between glycolysis scores and overall survival. Novel glycolysis-related subgroups were defined among the cell type with the highest glycolysis scores. Gene enrichment analysis, metabolic activity assessment, and univariate Cox regression were performed to explore the biological functions and prognostic impact of these subgroups. A prognostic risk model was built and validated based on genes significantly affecting the prognosis. Gene Set Enrichment Analysis (GSEA) was conducted to explore differences in biological processes between high- and low-risk groups. Differences in immune microenvironment and drug sensitivity between these groups were assessed using R packages. Potential targeted agents for prognostic risk genes were predicted using the Enrichr database. Results Tumor tissues showed significantly higher glycolysis scores than normal tissues, which was associated with a poor prognosis in CRC patients. The highest glycolysis score was observed in epithelial cells, within which we defined eight novel glycolysis-related cell subpopulations. Specifically, the P4HA1⁺ epithelial cell subpopulation was associated with a poor prognosis. Based on signature genes of this subpopulation, a six-gene prognostic risk model was formulated. GSEA revealed significant biological differences between high- and low-risk groups. Immune microenvironment analysis demonstrated that the high-risk group had increased infiltration of macrophages and tumor-associated fibroblasts, along with evident immune exclusion and suppression, while the low-risk group exhibited higher levels of B cell and T cell infiltration. Drug sensitivity analysis indicated that high-risk patients were more sensitive to Abiraterone, while low-risk patients responded to Cisplatin. Additionally, Valproic acid was predicted as a potential targeted agent. Conclusion High glycolytic activity is associated with a poor prognosis in CRC patients. The novel glycolysis-related prognostic risk model formulated in this study offers significant potential for enhancing the diagnosis and treatment of CRC.
Humans ; Colorectal Neoplasms/pathology* ; Glycolysis/genetics* ; Prognosis ; Transcriptome ; Tumor Microenvironment/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Kaplan-Meier Estimate

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Biosensors have become powerful tools for real-time monitoring of specific small molecules and precise control of gene expression in biological systems. High-throughput sensors for 1, 4-butanediamine biosynthesis can greatly improve the screening efficiency of high-yielding 1, 4-butanediamine strains. However, the strategies for adapting the characteristics of biosensors are still rarely studied, which limits the applicability of 1, 4-butanediamine biosensors. In this paper, we propose the development of a 1, 4-butanediamine biosensor based on the transcriptional regulator PuuR, whose homologous operator puuO is installed in the constitutive promoter P_gapA of Escherichia coli to control the expression of the downstream superfolder green fluorescent protein (sfGFP) as the reporter protein. Finally, the biosensor showed a stable linear relationship between the GFP/OD₆₀₀ value and the concentration of 1, 4-butanediamine when the concentration of 1, 4-butanediamine was 0-50 mmol/L. The promoters with different strengths in the E. coli genome were used to modify the 1, 4-butanediamine biosensor, and the functional properties of the PuuR-based 1, 4-butanediamine biosensor were explored and improved, which laid the groundwork for high-throughput screening of engineered strains highly producing 1, 4-butanediamine.
Biosensing Techniques/methods* ; Escherichia coli/metabolism* ; Promoter Regions, Genetic/genetics* ; Green Fluorescent Proteins/metabolism* ; Transcription Factors/genetics* ; Escherichia coli Proteins/genetics* ; Diamines/metabolism* ; Gene Expression Regulation, Bacterial

ObjectiveTo evaluate the effectiveness and safety of neck seven-line method combined with periauricular acupuncture as salvage treatment for sudden hearing loss in non-acute stage. MethodsSixty-six patients with non-acute stage of sudden hearing loss with a disease duration of 15-90 days were randomly divided into 33 cases each in treatment group and control group. The treatment group was given neck seven-line method combined with acupuncture at periauricular points； the control group used sham acupuncture and sham electroacupuncture at the same points. Both groups were treated 3 times a week for 6 weeks. The pure tone average hearing threshold of impaired frequencies were examined before treatment， after treatment finish and at follow-up （week 10）， and the difference between pure tone average hearing threshold of impaired frequencies before and after treatment was calculated； calculate the proportion of patients with ≥10 dB improvement in pure tone average hearing threshold of impaired frequency after treatment and at follow-up； compare the patients' Tinnitus Evaluation Scale （TEQ） scores， Chinese Medicine Quality of Life Assessment Scale （CQ-11D） health utility values and the difference between before and after treatment， and record the occurrence of adverse events. ResultsThe pure tone average of impaired frequency in the treatment group were （50.57±18.07） dB and （47.70±17.42） dB at post-treatment and follow-up respectively， and （54.38±21.77） dB and （53.36±20.99） dB in the control group at post-treatment and follow-up. Compared with the pre-treatment period， the pure tone average hearing threshold of impaired frequency in the two groups significantly decreased （P＜0.05） at post-treatment and follow-up. The difference of pure tone average hearing threshold of impaired frequency in the treatment group after treatment and at the follow-up visit compared to that before treatment was lower than those in the control group （P＜0.05）. After treatment， 13 patients （39.39%） in the treatment group and 10 patients （30.30%） in the control group showed improvement of ≥10 dB in pure tone average hearing threshold of impaired frequency； at the follow-up visit， 18 patients （54.55%） in the treatment group and 10 patients （30.30%） in the control group showed improvement of ≥10 dB in the pure tone average hearing threshold of impaired frequency， and there was no statistical significance for comparison between groups at the time of post-treatment and follow-up （P＞0.05）. The TEQ score of the treatment group significantly lower than that before treatment （P＜0.05）； the TEQ score of the treatment group and the difference between before and after treatment significantly lower than that of the control group （P＜0.05）. The difference in CQ-11D health utility values and the difference between before and after treatment were not statistically significant between the two groups （P＞0.05）. Eight cases of acupuncture-related adverse events occurred among 66 patients， including subcutaneous haematomas after needling， severe pain during needling and needle fainting， which disappeared after symptomatic treatment and did not affect the following treatment. ConclusionNeck seven-line method combined with periauricular acupuncture could be used as salvage treatment for sudden hearing loss in non-acute stage to improve the pure tone average hearing threshold of impaired frequency， alleviate tinnitus， with safety.

Objective To compare the early outcomes of domestic third-generation magnetically levitated left ventricular assist device (LVAD) with or without concomitant mitral valvuloplasty (MVP). Methods The clinical data of 17 end-stage heart failure patients who underwent LVAD implantation combined with preoperative moderate to severe mitral regurgitation in Fuwai Central China Cardiovascular Hospital from May 2018 to March 2023 were retrospectively analyzed. The patients were divided into a LVAD group and a LVAD+MVP group based on whether MVP was performed simultaneously, and early outcomes were compared between the two groups. Results There were 4 patients in the LVAD group, all males, aged (43.5±5.9) years, and 13 patients in the LVAD+MVP group, including 10 males and 3 females, aged (46.8±16.7) years. All the patients were successful in concomitant MVP without mitral reguragitation occurrence. Compared with the LVAD group, the LVAD+MVP group had a lower pulmonary artery systolic pressure and pulmonary artery mean pressure 72 h after operation, but the difference was not statistically different (P>0.05). Pulmonary artery systolic pressure was significantly lower 1 week after operation, as well as pulmonary artery systolic blood pressure and pulmonary artery mean pressure at 1 month after operation (P<0.01). There was no statistically significant difference in blood loss, operation time, cardiopulmonary bypass time, aortic cross-clamping time, mechanical ventilation time, or ICU stay time between the two groups (P>0.05). The differences in 1-month postoperative mortality, acute kidney injury, reoperation, gastrointestinal bleeding, and thrombosis and other complications between the two groups were not statistically significant (P>0.05). Conclusion Concomitant MVP with implantation of domestic third-generation magnetically levitated LVAD is safe and feasible, and concomitant MVP may improve postoperative hemodynamics without significantly increasing perioperative mortality and complication rates.

Objective To investigate the diagnostic value and clinical significance of hypersensitive C-reactive protein(hs-CRP),procalcitonin(PCT)combined with interleukin-6(IL-6)in children with severe hand-foot-mouth disease.Methods A total of 62 children hospitalized in our hospital from January 2022 to December 2022 were collected as research objects.According to the severity of infection,they were divided into observation group(severe infection group)with 29 cases and control group(mild infection group)with 33 cases.The differences of general data,total leukocyte count,neutrophil count,lymphocyte count,platelet count,hs-CRP,PCT,IL-6 and creatine kinase isoenzyme(CK-MB)between the two groups and their clinical applications were analyzed and compared.Results The total white blood cell count,neutrophil count,lymphocyte count,hs-CRP,PCT and IL-6 in the observation group were higher than those in the control group,and the difference has statistically significant.Receiver operator characteristic(ROC)curve analysis of hs-CRP predicted the sensitivity and specificity of severe infection of hand-foot-mouth disease were 79.3%and 93.9%(95%CI:0.852-10.985,P<0.05);The sensitivity and specificity of PCT were 93.1%and 84.8%(95%CI:0.907-1,P<0.05);The sensitivity and specificity of IL-6 were 96.6%and 87.9%(95%CI:0.945-1,P<0.05).Conclusions In hand-foot-mouth classification,PCT and IL-6 are highly sensitive.Although hs-CRP is less sensitive than the former,its specificity is higher than the former.Therefore,the combination of hs-CRP,PCT and IL-6 has higher value for hand-foot-mouth classification.

【Objective】 To monitor the effectiveness and accuracy of the blood transfusion compatibility test system by self-made weakly positive internal quality control products. 【Methods】 Red blood cells from DAT(-) healthy subjects were selected, and B/RhD(-)E(-) red blood cells were selected as tube 1. A/RhD(+ )E(+ ) was selected as tube 2 to prepare blood group quality control products according to the principle of blood group antigen compatibility, and red blood cell preservation solution and corresponding ABO blood group reagent antibody were added to make the agglutination intensity of microcolumn gel method in reverse blood typing reach a low positive value (1+ ). Tube 3 and tube 4 were prepared with five different preservation media: plasma, serum, antibody diluent, mixture of equal plasma and antibody diluent, and mixture of equal serum and antibody diluent, respectively. IgM anti-E antibody was added to tube 3, and IgG anti-D antibody was added to tube 4, so that the agglutination intensity of microcolumn gel method reached a low positive value (1+ ). 【Results】 Comparison between the 5 different preservation media showed that the preservation medium of antibody diluent was the most stable for weakly positive antibody (F=11.35, P<0.05), Agglutination intensity 1+ is assigned 5 points by AABB Technical Manual, and its score was 5.25±1.75 points. 【Conclusion】 The use of self-made weakly positive quality control products can improve the effectiveness, accuracy and sensitivity of the monitoring system, thus achieving internal quality control and ensuring the safety of clinical blood use.