OBJECTIVE: To explore the efficacy of a Thalassemia risk assessment software for the screening of thalassemia mutation carriers and distribution of thalassemia genotypes detected by screening. METHODS: A total of 6 040 individuals were evaluated at Leshan Maternal and Child Health Care Hospital between 2022 and 2024 using the commonly used clinical thalassemia risk assessment method and the thalassemia screening software, respectively, and the performance indicators of the two methods were compared and analyzed against the result of thalassemia gene testing. This study was approved by the Ethics Committee of our hospital (Ethics No.: LfyLL[2022]005). RESULTS: The high-risk rate by the thalassemia screening software was 11.19%, with a sensitivity of 95.12%, specificity of 93.28%, positive predictive value of 43.20%, negative predictive value of 99.72%, and the area under the ROC curve (AUC) was 0.942. The thalassemia gene detection rate of the high-risk samples screened was 4.83%. The high-risk screening rate of the conventional method was 2.50%, with a sensitivity of 51.22%, specificity of 93.28%, positive predictive value of 80.79%, negative predictive value of 97.40%, and the AUC was 0.754. The thalassemia gene detection rate of the high-risk samples was 2.02%. CONCLUSION The software can effectively detect thalassemia carriers and significantly reduce the missed detection compared with conventional method, thereby significantly improve the efficacy of screening.
Humans ; Thalassemia/diagnosis* ; Software ; Female ; Genetic Testing/methods* ; Male ; Mutation ; Adult ; Genotype ; ROC Curve ; Risk Assessment

Histone lactylation is a recently identified post-translational modification, wherein lactate mediates the enzymatic addition of lactyl groups to lysine residues on histones. Since its discovery, extensive research has demonstrated that histone lactylation is widely present in human tissues and plays a pivotal role in regulating the transcription of specific genes. Subsequent studies have further established this modification as a widespread epigenetic mark with significant physiological implications. With advancing research, accumulating evidence confirms that lactylation at distinct histone sites elicits diverse biological effects—such as promoting cell proliferation, driving inflammatory responses, and enhancing fibrosis—all of which profoundly influence disease progression and serve as key drivers of disease onset and development. Conversely, inhibiting histone lactylation can alter disease outcomes, positioning histone lactylation as a promising therapeutic target. Moreover, studies have revealed crosstalk between histone lactylation and other post-translational modifications, such as acetylation and methylation, which collectively regulate disease progression. Notably, lactylation occurs not only on histones but also on non-histone proteins. Histone lactylation activates specific gene transcription and reshapes metabolic epigenetics, while non-histone lactylation directly modulates enzyme activity, signal transduction, and protein stability. These two facets form a synergistic network through shared lactate pools, common modifying enzyme systems, and pathway crosstalk, thereby constructing a multi-dimensional regulatory framework—namely, the “histone lactylation-metabolism hub-non-histone lactylation” axis. This architecture bridges metabolism and epigenetics, and deciphering its topological structure may provide novel targets for precise intervention in diseases driven by lactate-mediated signaling hijacking. Traditional Chinese medicine (TCM), grounded in clinical practice, has been shown to regulate histone lactylation by modulating lactate metabolism and lactylation-related enzymes, thereby influencing disease progression. Moreover, certain TCM formulations exhibit potential as alternative therapies for drug-resistant diseases, underscoring the significance of further exploring TCM-mediated regulation of histone lactylation in future therapeutic strategies. This review aims to elucidate the mechanisms underlying histone lactylation, systematically delineate the associations between site-specific histone lactylation and various diseases, present a comprehensive landscape of the “lactate-histone lactylation and functional protein lactylation” axis, and summarize the mechanistic basis and research advances in TCM-mediated regulation of histone lactylation for disease treatment. Additionally, we discuss current challenges in histone lactylation research and propose future directions, ultimately aiming to deepen understanding and broaden perspectives on the roles and therapeutic potential of histone lactylation in disease.

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.

Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

The mammary gland is one of the most important glands in human body, and the abnormal changes of its tissue mechanics are often closely related to the occurrence and development of mammary gland diseases. With the development of two new interdisciplines, biomechanics and mechanobiology, their theoretical research results have been gradually transformed into clinical applications, resulting in two new clinical disciplines, mechanodiagnostics and mechanotherapy. However, many clinicians still lack a systematic and in-depth understanding of the biomechanical characteristics and mechanobiology of breast tissue, and their potential value in the clinical diagnosis and treatment of breast diseases. In view of this, we elaborated the evolution law of the biomechanical characteristics and mechanobiological mechanism of breast diseases from four aspects: breast biomechanics, breast mechanobiology, breast mechanodiagnostics, and breast mechanotherapy, analyzed their role in the occurrence and development of breast diseases, and discussed the mechanical principles involved in the traditional diagnosis and treatment of breast diseases, to provide new ideas and schemes for the diagnosis and treatment of breast diseases.

Objective:To investigate the relationship between serum interleukin-33(IL-33),interleukin-1 receptor-associated kinase 4(IRAK4),C-C chemokine receptor 5(CCR5)expression levels and patients with traumatic cerebral hemorrhage(TCH)complicate with acute ischemic stroke(AIS).Methods:162 TCH patients who were admitted to our hospital from March 2022 to January 2024 were selected,the patients were divided into AIS group and non-AIS group according to whether there was AIS in the early postoperative period.Serum IL-33,IRAK4 and CCR5 expression levels in AIS and non-AIS groups were compared,the predictive value of serum IL-33,IRAK4 and CCR5 expression levels in patients with TCH complicate with AIS was analyzed by receiver operating characteristic(ROC)curve,and the influencing factors of patients with TCH complicate with AIS were analyzed by multi-factor Logistic regression model.Results:Serum L-33,IRAK4 and CCR5 expression levels in AIS group were higher than those in non-AIS group(P＜0.05).Patients with TCH complicate with AIS were associated with Glasgow coma scale(GCS)score at admission,cerebral xenon,intraoperative hiatus incision and perioperative hypotension(P＜0.05).Low GCS score at admission,cerebral xenon,intraoperative hiatus incision,perioperative hyhyemia,high IL-33,high IRAK4 and high CCR5 were risk factors for patients with TCH complicate with AIS(P＜0.05).The ROC curve showed that the combination of serum IL-33,IRAK 4 and CCR5 had higher predictive value of patients with TCH complicate with AIS than testing alone(P＜0.05).Conclusion:Low GCS score at admission,cerebral xenon,intraoperative hiatus incision,perioperative hypostasis,high IL-33,high IRAK4 and high CCR5 are risk factors for patients with TCH complicate with AIS,and the predictive value of IL-33,IRAK4 and CCR5 for patients with TCH complicate with AIS is high.

Objective:To analyze the clinical characteristics, treatment response, and prognosis of patients newly diagnosed with immunoglobulin A multiple myeloma (IgA MM), and to ascertain whether the IgA isotype remains a poor prognostic factor in the bortezomib era.Methods:This study retrospectively enrolled 155 patients newly diagnosed with IgA MM and 420 with non-IgA MM admitted to the Department of Hematology, the First Affiliated Hospital of Nanchang University from March 2014 to December 2021. We compared the two groups in terms of their clinical characteristics, prognoses, and progression-free survival (PFS) and overall survival (OS) following different treatment regimens.Results:Compared with the non-IgA group, the IgA group presented with more aggressive clinical features, including a higher proportion of patients with hemoglobin<85 g/L (61.3% vs 51.4%, P=0.035), extramedullary manifestations (20.0% vs 11.4%, P=0.008), and gain/amp (1q21) (48.6% vs 36.7%, P=0.032). Efficacy analysis revealed a lower overall response rate (ORR) in the IgA group than in the non-IgA group (83.2% vs 92.4%, P=0.001). Among patients treated with bortezomib-based regimens, the ORR was 91.2% in the IgA group and 94.8% in the non-IgA group, but the difference was nonsignificant ( P=0.146). Survival analysis showed that the median PFS and OS were significantly shorter in the IgA group compared with the non-IgA group[23.5 (95% CI: 17.4-29.5) months and 48.8 (95% CI: 30.1-67.5) months vs 40.7 (95% CI: 33.8 - 47.6) months and not reached, respectively; P<0.001 and P=0.002]. In the subgroup of patients who received bortezomib-based therapy without subsequent autologous hematopoietic stem cell transplantation (auto-HSCT), the PFS and OS were significantly shorter in the IgA group compared with the non-IgA group[25.4 (95% CI: 18.7-32.1) months and 53.5 (95% CI: 35.4-71.6) months vs 41.0 (95% CI: 33.7-48.3) months and not reached; P=0.001 and P=0.011]. In patients who underwent bortezomib-based induction therapy followed by auto-HSCT, the 1-, 3-, and 5-year OS rates for the IgA group were 96%, 81%, and 81%, respectively, compared with 93%, 89%, and 79% for the non-IgA group, but the difference was nonsignificant ( P=0.758) . Conclusion:In the bortezomib era, IgA MM is still associated with a poorer overall prognosis than non-IgA MM, likely due to its inherent high-risk biological characteristics. Although bortezomib-based regimens effectively improve the treatment response, they fail to completely bridge the survival gap between the two disease isotypes. Therefore, bortezomib-based therapy followed by auto-HSCT may be a key strategy to overcome the poor prognosis of IgA MM, potentially enabling these patients to achieve long-term survival comparable to that of their non-IgA counterparts.

Objective:To explore the efficacy and safety of vagus nerve stimulation (VNS) combined with rehabilitation training in recovery of upper limb function in patients with ischemic stroke (IS) through Meta-analysis.Methods:Randomized controlled trials on upper limb motor dysfunction in IS patients accepted VNS published in PubMed, Web of Science, Embase, CNKI, Wanfang and VIP databases, and Chinese Biomedical Literature Database were retrieved. The retrieval period was from establishment of the databases to April 2025. Quality of the trials was assessed according to Cochrane handbook for systematic reviews of interventions (version 5.1). Two researchers independently screened the literature, extracted the data and evaluated the risk of bias of the included articles; and then, Meta-analysis was conducted by RevMan 5.4 software.Results:Eleven articles of randomized controlled trails were chosen, including 495 patients. Three articles were rated as A-level in terms of quality, and 8 were rated as B-level. Overall bias risk of the included studies was low. Results of Meta-analysis showed that compared with the control group (rehabilitation training alone), the intervention group (VNS combined with rehabilitation training) had significantly improved upper limb motor function (Fugl-Meyer assessment of upper limb motor function: standardized mean difference [ SMD]=0.77, 95% CI: 0.24-1.30, P<0.001) and activities of daily living (modified Barthel index: SMD=0.86, 95% CI: 0.56-1.16, P<0.001). Meanwhile, compared with those in the control group, incidence of adverse events ( RR=1.12, 95% CI: 0.95-1.33, P=0.170) and incidence of severe adverse events ( RR=1.67, 95% CI: 0.51-5.50, P=0.400) in the intervention group did not significantly increase. Results of subgroup analysis showed that compared with that in the control group, more significantly improved upper limb motor function was noted in patients from the non-invasive VNS intervention sub-group ( SMD=1.09, 95% CI: 0.46-1.72, P<0.001), intervention sub-group with a frequency of 5 times per week ( SMD=1.73, 95% CI: 0.58-2.87, P<0.001), and intervention sub-group with a duration of 4 weeks ( SMD=1.09, 95%CI: 0.72-1.47, P<0.001). Conclusion:VNS combined with rehabilitation training has good safety and efficacy in upper limb motor dysfunction after IS.