OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVES: To investigate the effect of moslosooflavone (MOS) for ameliorating dextran sulfate sodium (DSS)-induced colitis in mice and the underlying molecular mechanism. METHODS: C57BL/6J mice with or without DSS exposure in the drinking water were both randomized into two groups for treatment with intraperitoneal injections with MOS (200 mg/kg) or normal saline for 7 days (n=6). Disease severity of the mice was assessed by observing changes in body weight, colon length, histopathology (HE staining), intestinal barrier function, and TUNEL staining. In the in vitro studies, lipopolysaccharide (LPS)-stimulated mouse colon organoids were treated with MOS (120 μmol/L) for 24 h, and the changes in barrier dysfunction and inflammation were analyzed. Network pharmacology and Western blotting were employed to identify functional pathways and apoptotic protein regulation associated with the therapeutic effect of MOS on colitis. RESULTS: In the mouse models of DSS-indcued colitis, MOS treatment significantly reduced body weight loss, disease activity index (DAI) scores and colon shortening, ameliorated colonic histopathological changes and inflammation, and lowered pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, and IFN-γ). MOS effectively restored intestinal barrier integrity in the mice by reducing serum FITC-dextran and I-FABP concentrations while enhancing the tight junction proteins (ZO-1 and claudin-1). In the colon organoids, MOS significantly suppressed LPS-induced inflammatory responses and epithelial barrier disruption. Western blotting revealed that MOS downregulated C-caspase-3 and BAX and upregulated Bcl-2 expressions in both models. Mechanistically, MOS suppressed PI3K and AKT phosphorylation in both DSS-treated mouse colonic tissues and LPS-stimulated organoids. CONCLUSIONS MOS alleviates experimental colitis in mice by inhibiting intestinal epithelial apoptosis via inhibiting the PI3K/AKT pathway, thereby restoring intestinal barrier integrity and reducing inflammation.
Animals ; Dextran Sulfate ; Mice, Inbred C57BL ; Colitis/metabolism* ; Mice ; Signal Transduction/drug effects* ; Intestinal Mucosa/metabolism* ; Apoptosis/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Flavones/pharmacology* ; Male

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective:To compare the efficacy of the transverse process-lateral pedicle approach and curved vertebroplasty in the treatment of osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 66 patients with OVCF admitted to the Second People′s Hospital of Hefei from December 2021 to June 2023, including 9 males and 57 females aged 60-89 years [(75.6±7.5)years]. The injured segments included T 11 in 17 patients, T 12 in 17, L 1 in 17, and L 2 in 15. Among them, 33 patients underwent vertebroplasty via the transverse process-lateral pedicle approach (lateral approach group), while other 33 patients underwent curved vertebroplasty (curved group). The surgical duration, number of X-ray fluoroscopy, bone cement injection volume, and length of hospital stay were compared between the two groups. Additionally, the restoration efficiency of vertebral height and the correction degree of spinal scoliosis Cobb angle at 2 days postoperatively were compared between the two groups. The changes in serum levels of stress factors including noradrenaline, adrenaline, and cortisol preoperatively and at 2 days postoperatively, the visual analogue scale (VAS) and Oswestry disability index (ODI) preoperatively, at 2 days, 6 months postoperatively, and at the last follow-up were compared between the two groups. The incidence of complications was assessed in the two groups. Results:All the patients were followed up for 12-14 months [(13.2±0.5)months]. The surgical duration and number of X-ray fluoroscopy in the lateral approach group were (30.9±4.1)minutes and (5.9±3.3)times, which were significantly lower than (35.8±3.9)minutes and (9.9±4.4)times in the curved group ( P<0.01). There were no statistically significant differences between the two groups in terms of bone cement injection volume, length of hospital stay, restoration efficiency of vertebral height at 2 days postoperatively, or the correction degree of spinal scoliosis Cobb angle ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively were (57.3±4.8)ng/ml, (49.9±4.2)ng/ml, (159.3±20.5)nmol/L in the lateral approach group, and (64.3±4.5)ng/ml, (58.3±4.4)ng/ml, (183.5±21.2)nmol/L in the curved group, which were all significantly increased compared with those preoperatively [(42.3±3.5)ng/ml, (38.5±2.8)ng/ml, (128.4±12.3)nmol/L in the lateral approach group and (42.0±3.5)ng/ml, (39.0±3.0)ng/ml, (128.5±12.3)nmol/L in the curved group] ( P<0.01). There were no significant differences between the two groups in terms of the levels of noradrenaline, adrenaline, and cortisol preoperatively ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively in the lateral approach group were significantly lower than those in the curved group ( P<0.01). The VAS scores for low back pain in the lateral approach group and the curved group were 3(2, 5)points and 5(3, 6)points at 2 days postoperatively, 3(2, 4)points and 3(2, 4)points at 6 months postoperatively, and 2(2, 3)points and 2(2, 4)points at the last follow-up, which were all significantly lower than those preoperatively [7(7, 9)points and 8(6, 9)points] ( P<0.05). Moreover, the VAS scores for low back pain were further decreased over time postoperatively ( P<0.05). The ODI values in the lateral approach group and curved group were (33.4±4.4)% and (33.7±4.3)% at 2 days postoperatively, (23.8±1.6)% and (23.8±1.7)% at 6 months postoperatively, and (15.6±0.9)% and (15.6±0.9)% at the last follow-up, which were all significantly lower than (67.4±4.3)% and (67.5±4.3)% preoperatively ( P<0.05). Moreover, the ODI values were further decreased over time postoperatively ( P<0.05). There were no significant differences between the two groups in terms of the VAS scores for low back pain or ODI values preoperatively, at 2 days, 6 months postoperatively or at the last follow-up ( P>0.05). The complication rate was 12.1% (4/33) in the lateral approach group, which was significantly lower than 51.5% (17/33) in the curved group ( P<0.05). Conclusion:Although both the transverse process-lateral pedicle approach vertebroplasty and the curved vertebroplasty can achieve good therapeutic effects in the treatment of OVCF, the former has shorter surgical duration, fewer times of X-ray fluoroscopy, lower trauma stress levels at 2 days postoperatively, and fewer complications.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Medical record homepage is a core basis for healthcare quality management, medical insurance payment, and public hospital performance evaluation.The completeness and accuracy of its data directly affect the medical quality and economic benefits of hospitals. Since July 2022, a tertiary hospital had built an auxiliary decision-making system for diagnosis omissions based on artificial intelligence technology, which was officially launched in January 2023. The system aimed to improve the quality of data on the first page of medical records and ensure reasonable payment by medical insurance. This system was built on the hospital′s electronic medical records, and integrated natural language processing, medical knowledge graphs and deep learning technologies to create three engines: diagnosis omission recognition, ICD coding and DRG grouping. The diagnosis omission recognition engine identified both explicit and implicit omitted diagnoses by using a context semantic analysis model and a contrastive learning framework for dual judgment. It also interacted with the ICD coding and DRG grouping engines to enhance the accuracy of DRG grouping. Since its launched, the system has achieved remarkable results. A comparative analysis revealed that the rate of missing diagnoses on hospital medical record homepages has decreased from 31.31% during January to September 2022 to 12.34% during the same period in 2023, and the quality control time for a single medical record had been reduced from 20 minutes to 5 minutes. Additionally, a simulation calculation showed that the system-assisted DRG grouping can increase the hospital′s medical insurance surplus. The system could provide reference and guidance for public hospitals in China to improve the quality of the homepage of medical records and better adapt to medical insurance payment reform.

Alcohol use disorder(AUD)is a common mental disorder and physiological disease impac-ting millions globally.Although multiple studies have explored the causes and treatments of AUD,its exact mechanisms remain poorly understood.The development of lipidomics technology provides a new perspective for studying AUD and can be used to investigate its biological mechanisms.This review summarizes recent ap-plications and progress of lipidomics in AUD research,as well as its potential value in prevention and treat-ment strategies.

Under the guidance of five-viscus correlation theory,and with reference to the clinical practice,this paper discusses the pathogenesis of cardiogenic asthma,i.e.long illness of the heart resulting in asthma,from the perspective of physiological characteristics of heart,which belongs to yin in essence and yang in function.And this paper also introduces the correlation between five zang-organs and cardiogenic asthma:asthma induced by heart failure involves the lung,has close relation with middle energizer(spleen and stomach),results from the comorbidity of heart and liver,and contributes to the disorders of kidney.It is believed that cardiogenic asthma injures the heart,results in internal blockage of blood stasis,so the original pathogenesis of cardiogenic asthma is due to the heart;unsmoothed blood circulation causes fluid retention in the chest and lung,and then the lung is involved.The failure of spleen and stomach in generation and transportation will cause the unsmoothed circulation of qi and blood,liver qi stagnation will result in the failure of liver blood in nourishment,and the intense kidney yin-fire will stir upward and attack heart yang.The factors mentioned above all are prone to result in the aggravation of cardiogenic asthma.Therefore,the treatment of cardiogenic asthma with traditional Chinese medicine should be focused on heart,and methods of replenishing qi,activating blood circulation,and inducing diuresis are used as the primary therapeutic approaches.Moreover,according to the organs involved in cardiogenic asthma,therapies of regulating the five viscera and restoring the balance of yin and yang are used for precise treatment,and the therapeutic effect will be enhanced.

Alzheimer's disease(AD)is the most common cause of cognitive impairment in the elderly,and the formation of intracellular neurofibrillary tangles(NFT)due to the hyperphos-phorylation of Tau is one of its important pathological features.Compared to β-amyloid,the hyperphosphorylation of Tau and the resulting NFT are more closely related to the decline in cognitive ability.This review focuses on anti-AD drugs targeting Tau,em-phasizing the latest progress in inhibiting the hyperphosphoryla-tion of Tau protein,alleviating the aggregation of Tau protein,re-ducing the cytoskeletal damage caused by the hyperphosphoryla-tion of Tau protein by stabilizing microtubules,and immunothera-py,in the hope of providing new insights into drug research for AD and related cognitive disorders associated with Tau protein.