Chronic myeloid leukemia (CML) is a malignant hematologic disorder caused by abnormal proliferation of hematopoietic stem cells. In recent years, while the application of tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis of CML patients through in-depth exploration of pathogenesis of CML and advancements in targeted therapies, some patients still face challenges including drug resistance, disease relapse, and failure to achieve treatment-free remission. Imunotherapy, as a complementary or alternative strategy, holds significant potential for overcoming these limitations, and has gradually emerged as a critical research focus in CML treatment. This review aims to summarize the current research status and latest advances in immunotherapy for CML.

Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

Objective To investigate the correlations of the expression levels of serum silencing in-formation regulatory factor 2-related enzyme 1(SIRT1),endothelial cell-specific molecule-1(ESM-1),and fibroblast growth factor-21(FGF21)with therapeutic outcome in patients with sepsis-related acute respiratory distress syndrome(ARDS).Methods A total of 140 patients with sepsis-related ARDS were selected and divided into good outcome group(n=96)and poor outcome group(n=44)accord-ing to the therapeutic outcome.The levels of serum SIRT1,ESM-1 and FGF21 were compared between the two groups,and the correlations of serum SIRT1,ESM-1 and FGF21 with the severity of the dis-ease and therapeutic outcome were analyzed.The predictive values of serum SIRT1,ESM-1 and FGF21 for therapeutic outcome were evaluated.Results The serum SIRT1 level in the poor outcome group was significantly lower,while the levels of ESM-1 and FGF21 were significantly higher than those in the good outcome group(P＜0.05).The serum SIRT1 level showed a significant gradual downward trend in mild,moderate,and severe patients,while the ESM-1 and FGF21 levels showed a significant gradual upward trend in mild,moderate,and severe patients(P＜0.05).Spearman corre-lation analysis showed that serum SIRT1 was significantly negatively correlated with disease severity,while ESM-1 and FGF21 were significantly positively correlated with disease severity(P＜0.05).Partial correlation analysis showed that serum SIRT1,ESM-1 and FGF21 were significantly correla-ted with the therapeutic outcome of ARDS patients with sepsis(P＜0.05).The receiver operating characteristic(ROC)curve showed that the area under the curve(AUC)of serum SIRT1,ESM-1 and FGF21 for predicting the treatment outcome of sepsis-related ARDS patients was 0.742,0.838 and 0.796 respectively,with sensitivities of 77.27％,77.27％and 70.45％,and specificities of 64.58％,81.25％and 87.50％.The AUC of the combination of three indexes for predicting the therapeutic outcome of sepsis-related ARDS patients was 0.939,with a sensitivity of 88.64％and a specificity of 83.33％,which was significantly higher than the predictive value of the three indexes alone(P＜0.05).Conclusion The levels of SIRT1,ESM-1 and FGF21 in the serum of sepsis-re-lated ARDS patients are significantly correlated with the severity of the disease and the therapeutic outcome,and have the abilitis to independently predict the therapeutic outcome.The combined pre-dictive value is even higher.

Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the present study,an innovative natural product virtual screening-interaction-phenotype(NP-VIP)strategy that integrates virtual screening,chemical proteomics,and metabolomics to identify and validate the bioactive targets of NPs.This approach reduces false positive results and enhances the ef-ficiency of target identification.Salvia miltiorrhiza(SM),a herb with recognized therapeutic potential against ischemic stroke(IS),was used to illustrate the workflow.Utilizing virtual screening,chemical proteomics,and metabolomics,potential therapeutic targets for SM in the IS treatment were identified,totaling 29,100,and 78,respectively.Further analysis via the NP-VIP strategy highlighted five high-confidence targets,including poly[ADP-ribose]polymerase 1(PARP1),signal transducer and activator of transcription 3(STAT3),amyloid precursor protein(APP),glutamate-ammonia ligase(GLUL),and glutamate decarboxylase 67(GAD67).These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM.The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research,proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

Objective: To develop a rapid quantification method for neutrophil extracellular traps (NETs) by quantifying neutrophils forming NETs (NETotic cells) on routine peripheral blood smears, and to evaluate the performance of an early warning model combining NETs with traditional coagulation indicators for risk of sepsis-induced coagulopathy (SIC) in septic patients. Methods: This prospective observational study was conducted in Wuxi People's Hospital Affiliated with Nanjing Medical University between May 2023 and May 2025. A total of 147 patients with sepsis (diagnosed based on Sepsis-3.0 criteria) who had not developed SIC [the international society on thrombosis and haemostasis (ISTH SIC score <4)] were enrolled. Blood samples were collected within 2 hours of admission. Neutrophil smudge cells (NETs%) were counted using an automated cell morphology analyzer. Serum levels of myeloperoxidase-DNA (MPO-DNA) complexes, circulating free DNA (cf-DNA) and sequential organ failure assessment (SOFA) scores were also determined. Based on progression to SIC (ISTH score ≥4) within 72 hours of admission, patients were categorized into a sepsis without SIC group (n=85) and a sepsis with SIC group (n=62). Risk factors were analyzed using binary logistic regression, receiver operating characteristic (ROC) curves were plotted, and the predictive value of NETs%, SOFA, and AT-Ⅲ for coagulation dysfunction was assessed. Results: The NETs% level was significantly higher in the sepsis with SIC group [8.50% (7.00, 11.50)] compared to both the healthy control group [1.00% (0.00, 2.00)] and sepsis without SIC group [4.40%(3.50, 6.50)] (P<0.01). NETs% was identified as an independent risk factor for SIC in sepsis patients. ROC analysis showed that the area under the curve (AUC) for predicting SIC was 0.90 for NETs%, 0.85 for MPO-DNA, and 0.79 for cf-DNA. The combined model of NETs% and SOFA score demonstrated the best performance, with an optimal cut-off value of 0.33, an AUC of 0.92, a sensitivity of 77%, and a specificity of 93%. Conclusion: NETs% shows promise as a novel biomarker for SIC. Peripheral blood smear morphology provides a simple, rapid, and cost-effective method for quantifying NETs%. NETs% enhances the early clinical identification of patients at high risk for SIC, and its combination with the SOFA score facilitates SIC prediction, offering a critical time window for initiating timely preventive interventions.

Objective:To explore the genetic etiology of a child with primary hypertrophic osteoarthropathy(PHO).Methods:A child who was admitted to Zhongnan Hospital of Wuhan University on July 27, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing. Suspected splicing variant was verified by Sanger sequencing of family members. In vitro function was validated through a minigene assay, whilst the suspected exonic deletion was validated by long-fragment PCR. This study was approved by the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-011). Results:Whole exome sequencing revealed that the child has harbored compound heterozygous variants of HPGD gene, including a heterozygous deletion (Exon 3 del) derived from his father and a splicing variant (c.421+ 1G>T) derived from his mother. Long-fragment PCR verified that the child and his father had both harbored a 7 565 bp heterozygous deletion (c.218-1304_324+ 6156del), whilst the minigene assay proved that the splicing variant has resulted in skipping of exon 4. Conclusion:The heterozygous c. 218-1304_324+ 6156del deletion and the c. 421+ 1G>T splicing variant of the HPGD gene probably underlay the pathogenesis in this child. Above finding has enriched the mutational spectrum of the HPGD gene and provided a basis for genetic counseling and prenatal diagnosis for this family.

We will review a case of adrenal aldosterone-cortisol co-producing adenoma (A/CPA) admitted to our hospital on May 7, 2021. By reviewing the clinical courses of this case and its relevant literatures, we hope to improve the understanding and treatment level of this disease.

Objective To evaluate the degree of brain atrophy in spinocerebellar ataxia type 3(SCA3)patients based on artificial intelligence(AI)technology,and to explore the correlation between the degree of brain atrophy and the severity of the disease.Methods The clinical and imaging data of 23 SCA3 patients(SCA3 group)and 24 healthy controls(HC)(HC group)were collected.The International Cooperative Ataxia Rating Scale(ICARS)was used to evaluate the severity of ataxia in patients with SCA3.AI technology was used to process the 3D-T1 WI MR image data of the SCA3 and HC groups to segment and measure the volume and volume percentage of brain,followed by correlation analyses between brain structural alterations and the severity of ataxia in SCA3 patients.Results There were no significant differences in gender and age between the two groups(P＞0.05).The SCA3 group had a significant reduction in the volume and volume percentage of various brain regions,such as the frontal,temporal,parietal,occipital,limbic,right cerebral white mat-ter,subcortical gray matter,cerebellum and brainstem,compared to the HC group(multiple hypothesis testing adjusted P＜0.01).In the SCA3 group,the ICARS showed positive correlation with patient age(r=0.571,P=0.004)and negative correlation with the vol-ume of the left cerebellar white matter,vermis,medulla oblongata,and the volume percentages of bilateral cerebellar white matter,vermis,pons,medulla oblongata(P＜0.05).Conclusion The significant atrophy of the supratentorial and subtentorial regions of the brain in SCA3 patients.The globus pallidus exhibits the most substantial atrophy,suggesting its potential as an imaging diagnostic marker of SC A3.

Heart failure is a fatal stage of end-stage cardiovascular disease,which brings a huge medical burden to the society because of its high mortality and re-hospitalisation rates.Intestinal microecology is the largest and most com-plex microecosystem of human body.It is inhabited by tens of thousands of microorganisms in human gastrointestinal tract.In recent years,with the deepening of the study of intestinal flora,more and more studies have found that the im-balance of intestinal microecology can cause changes of metabolites in heart failure patients,which is one of the key triggers for the development of heart failure,therefore,using the intestinal microbial homeostasis as a new entry point for the treat-ment of heart failure will be a hotspot in medical research.However,the theory of Chinese medicine,"the spleen is the guardian",covers the physiological functions of the spleen,such as the spleen's main function of transporting,spleen's main function of ascending and clearing,and its main function of hiding camping,etc.,and the functions of intestinal flora and the"spleen is the guardian"are similar to a certain extent.Therefore,this paper starts from a holistic viewpoint and takes the theory of"spleen as the guardian"in Chinese medicine as an entry point to elaborate on the pathogenesis of intes-tinal microecological imbalance and heart failure,so as to provide a reference for Chinese medicine treatment or drug re-search.

Diabetic peripheral neuropathy (DPN) is one of common chronic complications associated with diabetes. In recent years, high-frequency ultrasound, ultrasound elastography, and contrast-enhanced ultrasound have prodived novel approaches for DPN diagnosis. High-frequency ultrasound can effectively demonstrate the morphological alterations of the peripheral nerves, thereby establishing a morphological foundation for DPN diagnosis. Ultrasound elastography can reflect the functional status of the nerves affected by DPN by measuring the elastic changes of the peripheral nerves. Furthermore, contrast-enhanced ultrasound can be utilized to observe the blood perfusion of the target nerves, evaluate microcirculatory alterations in nerve tissue, and serve as references for DPN diagnosis. This paper reviews the progress of high-frequency ultrasound, ultrasound elastography, and contrast-enhanced ultrasound in DPN diagnosis, aiming to provide references for application and promotion of these new ultrasound techniques in DPN early diagnosis.