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 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.

Cognitive dysfunction refers to dysfunction of individual perception,memory,understanding,learning,creation and other dysfunctions caused by abnormal brain function and structure.Based on the fact that the spleen can't regulate transportation and transformation,govern blood and send up essential substance,combined with the microbiota-gut-brain axis,this article discussed the etiology and pathogenesis of intestinal flora imbalance affecting cognitive dysfunction in TCM.It was proposed that the spleen in TCM and intestinal flora are connected in physiology and pathology:the spleen regulates spirit and governs cognition,when the spleen fails to function normally that it can't dominate transportation and transformation,govern blood and send up essential substance will cause that the brain spirit can not be nourished;intestinal flora is closely related to the spleen in TCM,and affects brain function through the nervous system,endocrine,immune and metabolic mechanisms.This article can provide explore new ideas for the clinical research and treatment of cognitive dysfunction of traditional Chinese and Western medicine.

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.

Objective:To compare the effectiveness, safety and postoperative recurrence of percutaneous nephrolithotomy (PCNL) with Holmium laser for upper urinary calculi in Uyghur and Han pediatric patients.Methods:The data of 123 Uyghur and 71 Han pediatric patients with upper urinary calculi admitted to First People's Hospital of Kashgar, Xinjiang and Beijing Friendship Hospital, Capital Medical University respectively, from August 2018 to August 2023, were retrospectively reviewed. The gender [males 73 (59.3%) vs.46 (64.8%) ], laterality (single/bilateral: 94/29 vs. 59/12), hydronephrosis [115 (93.5%) vs. 63 (88.7%)] and anatomical abnormalities [2(1.6%) vs. 5(7.0%)] of Uyghur and Han children were not statistically significant ( P>0.05). Uyghur children were older than Han children [5 (3, 7) vs. 3 (2, 6) years old], with a higher proportion of emaciated children [27 (21.9%) vs. 6 (8.5%) cases], a larger maximum stone diameter [(2.30±0.78) vs. (1.96±1.50) cm] and a lower proportion of multiple stones [46 (37.4%) vs. 52 (73.2%) cases] (all P<0.05). All the patients were treated with Holmium laser PCNL. The channels of the procedures in this study include F12-18 small channels and visual puncture channels. The operation datas, stone-free rate (SFR), complication rate (CR) and stone recurrence rate of the two groups were compared. Meanwhile, multiple logistic regression analysis was used to explore the factors influencing these indicators. Results:The operation time for Uyghur children was significantly longer than that of Han children [75.0 (58.0, 93.0) vs. 30.0 (20.0, 48.8) min]. Additionally, a greater proportion of Uyghur children underwent PCNL with F12-18 small channels than Han children [119 (96.7%) vs. 49(69.0%) cases]. The SFR [89.4%(110/123)vs.88.7%(63/71)], and postoperative CR [31.7%(39/123)vs. 26.8%(19/71)] in Uyghur and Han patients were not significantly different (all P>0.05). The recurrence rate in Uyghur children was higher than that observed in Han children [28.1%(25/89) vs. 15.6%(10/64), P=0.033]. The multivariate logistic regression analysis results indicated that the maximum stone diameter was an independent risk factor for SFR in both groups ( OR=0.401, 95% CI 0.191-0.842, P=0.016). Similarly, maximum stone diameter ( OR=1.896, 95% CI 1.088-3.304, P=0.024) and multiple stones ( OR=3.225, 95% CI 1.409-7.384, P=0.024) were identified as independent risk factors for CR. Ethnicity was not independent risk factor for SFR( OR=0.679, 95% CI 0.215-2.140), CR( OR=1.047, 95% CI 0.495-2.215) and stone recurrence rate( OR=0.820, 95% CI 0.285-2.356, all P>0.05). Conclusions:In comparison to Han pediatric patients during the same period, Holmium laser PCNL had similar SFR and CR for treating Uyghur children with upper urinary calculi, who were older, more emaciated and had larger average stone diameters. The higher postoperative recurrence rate of Uyghur children is likely to be associated with higher stone burden. The multivariate logistic regression analysis results showed that ethnicity was not an influential factor in SFR, complication rates, and stone recurrence rates. The findings need to be further validated in larger prospective cohort studies.

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.

Objective:To observe the effect of rhGLP-1 (7-36) on Akt/GSK3 signaling pathway in hepatocytes.Methods:Human HL7702 cell line was cultured to the logarithmic growth stage and divided into experimental group and blank control group. The cultures were incubated with 100nM medium containing rhglp-1 (7-36) and without rhglp-1 (7-36) for 90min. The levels of Akt, Glycogen synthase Kinase 3 (GSK3) and Glycogen synthase (GS) in the two groups were detected by Western Blot.Results:Compared with blank control group, the protein expression of p-Akt (Thr308) in experimental group (1.81±0.28) was significantly increased ( P=0.01), but the protein expression of Akt and p-Akt (Ser473) was not significantly changed. The protein expression levels of p-GSK3α (Ser21) (1.27±0.09) and p-GSK3β (Ser9) (1.24±0.09) in the experimental group were significantly increased ( P=0.003, 0.002), while the protein expression levels of GSK3α and GSK3β were not significantly changed. The protein expression level of p-GS (Ser641) (0.70±0.16) was decreased in the experimental group ( P=0.03), but the protein expression level of GS did not change significantly. Conclusion:Glp-1 can inhibit GSK3/GS signaling pathway, activate GS activity and promote glycogen synthesis.