ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase （ERK） signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group， the model mice were randomly divided into the model group， Guiqi Yiyuan ointment low， medium， and high dose groups， and the extracellular ERK1/2 inhibitor group， with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75， 3.5， 7.0 g·kg^-1·d^-1 for the low， medium， and high dose groups， respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 （100 mg·kg^-1·d^-1） by gavage. The treatment was administered for 14 consecutive days， after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1 （PD-L1） in tumor tissues. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of p-ERK1/2， PD-L1， the autophagy marker Beclin-1， the autophagic protein p62， and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group， the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and markedly reduced in the high dose and inhibitor groups （P<0.01）. Tumor cells in all treatment groups became progressively irregular， with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased， and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and significantly reduced in the high dose and inhibitor groups （P<0.01）. The mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， while LC3Ⅰ/Ⅱ mRNA expression was elevated （P<0.05）. In the high dose and inhibitor groups， mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ mRNA expression was significantly increased （P<0.01）. Protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， and LC3Ⅰ/Ⅱ protein expression was elevated （P<0.05）. In the high dose and inhibitor groups， protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ protein expression was significantly elevated （P<0.01）. ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway， downregulate the expression of p-ERK1/2， promote autophagic flux in tumor cells， and regulate the expression of PD-L1， thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

ObjectiveTo evaluate the clinical efficacy and safety of Huaban Jiedu Formulation （化斑解毒方， HJF） in treating psoriasis vulgaris with blood-heat syndrome. MethodsA randomized， double-blind， placebo-controlled study was conducted with 60 patients diagnosed with psoriasis vulgaris of blood-heat syndrome. Patients were randomly assigned to either a treatment group or a control group， with 30 cases in each. The treatment group received HJF granules orally， one dose a day， combined with topical Qingshi Zhiyang Ointment （青石止痒软膏）， while the control group received placebo granules， one dose a day， combined with the same topical ointment. Both groups were topically treated twice daily of 28 days treatment cours. Psoriasis area and severity index （PASI）， visual analogue scale for pruritus （VAS）， traditional Chinese medicine （TCM） syndrome scores， dermatology life quality index （DLQI）， and psoriasis life stress inventory （PLSI） were assessed before treatment and on day 14 and day 28. Response rates for PASI 50 （≥50% reduction） and PASI 75 （≥75% reduction）， as well as overall clinical efficacy， were compared between groups. Serum levels of interleukin-6 （IL-6） and interleukin-17 （IL-17） were measured before and after 28 days of treatment. Adverse reactions during treatment were recorded. ResultsAfter 28 days of treatment， both groups showed significant reductions in PASI total score， lesion area score， erythema， scaling， and infiltration scores， pruritus VAS score， TCM syndrome score， DLQI， PLSI， and serum IL-6 and IL-17 levels （P＜0.05）. Compared to the control group， the treatment group had significantly greater improvements in PASI total score and erythema score， TCM syndrome score， serum IL-6 and IL-17 levels， and PASI 50 response rate after 28 days （P＜0.05）. Between-group comparisons of score differences before and after 28-day treatment revealed that the treatment group showed significantly better improvements in PASI total， lesion area score， erythema score， TCM syndrome score， DLQI， PLSI， and inflammatory markers （P＜0.05 or P＜0.01）. The total effective rate on day 14 and day 28 was 40.00% （12/30） and 83.33% （25/30） in the treatment group， versus 6.90% （2/29） and 41.38% （12/29） in the control group， respectively. The clinical efficacy in the treatment group was significantly superior to that in the control group （P＜0.05）. Mild gastric discomfort occurred in 3 patients in the treatment group and 1 in the control group. ConclusionHJF can effectively improve skin lesions and TCM symptoms relieve pruritus， enhance quality of life， and reduce inflammatory markers IL-6 and IL-17， in patients with blood-heat syndrome of psoriasis vulgaris， with a good safety profile.

Cardiovascular diseases and psychological disorders represent two major threats to human physical and mental health. Research on electrocardiogram (ECG) signals offers valuable opportunities to address these issues. However, existing methods are constrained by limitations in understanding ECG features and transferring knowledge across tasks. To address these challenges, this study developed a multi-resolution feature encoding network based on residual networks, which effectively extracted local morphological features and global rhythm features of ECG signals, thereby enhancing feature representation. Furthermore, a model compression-based continual learning method was proposed, enabling the structured transfer of knowledge from simpler tasks to more complex ones, resulting in improved performance in downstream tasks. The multi-resolution learning model demonstrated superior or comparable performance to state-of-the-art algorithms across five datasets, including tasks such as ECG QRS complex detection, arrhythmia classification, and emotion classification. The continual learning method achieved significant improvements over conventional training approaches in cross-domain, cross-task, and incremental data scenarios. These results highlight the potential of the proposed method for effective cross-task knowledge transfer in ECG analysis and offer a new perspective for multi-task learning using ECG signals.
Humans ; Electrocardiography/methods* ; Mental Health ; Algorithms ; Signal Processing, Computer-Assisted ; Machine Learning ; Arrhythmias, Cardiac/diagnosis* ; Cardiovascular Diseases ; Neural Networks, Computer ; Mental Disorders

Objective:To summarize the clinical, pathological and molecular characteristics of various types of pediatric glioma, and to explore the differences in the morphology and clinical significance among various types of pediatric glioma.Methods:Based on the fifth edition of the World Health Organization classification of central nervous system tumors, this study classified or reclassified 111 pediatric gliomas that were diagnosed at Guangzhou Medical University Affiliated Women and Children′s Medical Center from January 2020 to June 2023. The clinical manifestations, imaging findings, histopathology, and molecular characteristics of these tumors were analyzed. Relevant literature was also reviewed.Results:The 111 patients with pediatric glioma included 56 males and 55 females, with the age ranging from 10 days to 13 years (average age, 5.5 years). Clinically, manifestations presented from 5 days to 8 years before the diagnosis, including epilepsy in 16 cases, increased intracranial pressure in 48 cases and neurological impairment in 66 cases. MRI examinations revealed tumor locations as supratentorial in 43 cases, infratentorial in 65 cases, and spinal cord in 3 cases. There were 73 cases presented with a solid mass and 38 cases with cystic-solid lesions. The largest tumor diameter ranged from 1.4 to 10.6 cm. Among the 111 pediatric gliomas, there were 6 cases of pediatric diffuse low-grade glioma (pDLGG), 63 cases of circumscribed astrocytoma glioma (CAG), and 42 cases of pediatric diffuse high-grade glioma (pDHGG). Patients with pDLGG and CAG were younger than those with pDHGG. The incidence of pDLGG and CAG was significantly lower in the midline of the infratentorial region compared to that of pDHGG. They were more likely to be completely resected surgically. The pDLGG and CAG group included 4 cases of pleomorphic xanthoastrocytoma, showing histological features of high-grade gliomas. Among the high-grade gliomas, 13 cases were diffuse midline gliomas and also showed histological features of low-grade glioma. Immunohistochemical studies of H3K27M, H3K27ME3, p53, ATRX, BRAF V600E, and Ki-67 showed significant differences between the pDLGG and CAG group versus the pDHGG group ( P<0.01). Molecular testing revealed that common molecular variations in the pDLGG and CAG group were KIAA1549-BRAF fusion and BRAF V600E mutation, while the pDHGG group frequently exhibited mutations in HIST1H3B and H3F3A genes, 1q amplification, and TP53 gene mutations. With integrated molecular testing, 2 pathological diagnoses were revised, and the pathological subtypes of 35.3% (12/34) of the pediatric gliomas that could not be reliably classified by histology were successfully classified. Conclusions:There are significant differences in clinical manifestations, pathological characteristics, molecular variations, and prognosis between the pDLGG, CAG and pDHGG groups. The integrated diagnosis combining histology and molecular features is of great importance for the accurate diagnosis and treatment of pediatric gliomas.

OBJECTIVE To systematically evaluate the efficacy and safety of thalidomide combined with aclacinomycin， granulocyte colony-stimulating factor and cytarabine （CAG） regimen in the treatment of elderly patients with acute myeloid leukemia （AML）. METHODS CNKI， Wanfang data， VIP， Sino Med， PubMed， Embase， the Cochrane Library and Web of Science were searched comprehensively from the inception to Aug. 27th， 2023. Randomized controlled trials （RCTs） about thalidomide combined with CAG regimen （trial group） versus CAG regimen （control group） in the treatment of elderly AML patients were collected， and RevMan 5.3 software was used for meta-analysis of included studies. RESULTS Finally， 7 RCTs were included， with a total of 601 patients， including 307 patients in the trial group and 294 patients in the control group. Meta-analysis results showed that the trial group was superior to the control group in enhancing the overall response rate [Z＝4.75， P＜0.000 01， OR＝2.80， 95%CI （1.83，4.28）]， complete remission rate [Z＝2.82， P＝0.005， OR＝1.61， 95%CI （1.16， 2.25）]， and improving platelet count [Z＝2.70， P＝0.007， MD＝64.02， 95%CI （17.53， 110.51）]， vascular endothelial growth factor [Z＝13.63，P＜0.000 01， MD＝－65.17， 95%CI（－74.54， －55.80）]， vascular endothelial growth factor receptor [Z＝12.03， P＜ 0.000 01， MD＝－499.01， 95%CI （－580.31， －417.71）] and basic fibroblast growth factor [Z＝4.17， P＜0.000 1，MD＝－0.23， 95%CI（－0.35， －0.12）]. And there was no statistical difference between the trial group and the control group in the incidence of adverse drug reaction [Z＝0.99， P＝0.32， OR＝0.52， 95%CI（0.14，1.89）]， nausea and vomiting [Z＝ 1.06， P＝0.29， OR＝0.66， 95%CI （0.30，1.43）]， constipation or diarrhea [Z＝0.92， P＝0.36， OR＝0.65， 95%CI（0.26， 1.63）]， drowsiness [Z＝1.38， P＝0.17， OR＝0.57， 95%CI（0.26， 1.27）] or myelosuppression [Z＝0.88，P＝0.38，OR＝0.68，95%CI（0.28， 1.62）]. CONCLUSIONS The combination of thalidomide and CAG regimen in the treatment of elderly AML patients can significantly improve clinical efficacy and has high safety.

Objective To observe the effects and mechanism of Guiqi Yiyuan Ointment on immune function in 12C6+ beam bystander-effect rats.Methods Totally 60 Wistar rats were randomly divided into blank group,model group,positive control group,and TCM low-,medium-,and high-dosage groups,with 10 rats in each group.TCM low-,medium-,and high-dosage groups were given 1.2,2.4,and 4.8 g/kg Guiqi Yiyuan Ointment for gavage,and the blank group,model group and positive control group were given equal dose of sodium chloride solution for gavage for 14 days.Positive control group received intraperitoneal injection of amifostine 30 minutes before modeling.On the 15th day,except the blank group,the other groups were given 4 Gy 12C6+ beam of single irradiation on the right lung.After irradiation,each group was given gavage for 3 days.The general condition of rats was observed,peripheral blood leukocyte(WBC),red blood cell(RBC),hemoglobin(Hb),platelet(PLT)levels were detected,ELISA was used to detect the contents of serum interleukin(IL)-4 and interferon-γ(IFN-γ),lung and spleen organ indices were calculated,HE staining was used to observe the pathological morphology of left lung and spleen tissues,and flow cytometry was used to detect the proportion of CD4+ and CD8+ T lymphocytes in the spleen,qPCR was used to detect the expressions of T-bet and GATA-3 mRNA in right lung and spleen tissues.Results Compared with the blank group,the model group rats showed a decrease in peripheral blood WBC,an increase in RBC,Hb,PLT,and an decrease in serum IL-4 and IFN-γ contents;the organ indices of left lung and spleen was significantly reduced,the alveoli were deformed,the alveolar walls became thicker,the alveolar cavities shrank,the lung tissue was significantly bleeding,the spleen tissue structure was severely damaged,the splenic sinus cavity became narrower,and the splenic cord showed fibrous hyperplasia;the proportion of CD4+ T lymphocytes and CD4+/CD8+ ratio in spleen tissue of the model group decreased,while the proportion of CD8+ T lymphocytes increased,the expression of T-bet mRNA in the left lung and spleen tissues decreased,while the expression of GATA-3 mRNA increased,with statistical significance(P<0.05).Compared with the model group,the positive control group and TCM medium-and high-dosage groups showed an increase in peripheral blood WBC,an decrease in RBC,Hb,PLT,an increase in serum IL-4 and IFN-γ contents;the index of left lung and spleen organs increased in TCM high-dosage group;the pathological damage of left lung and spleen tissues in each treatment group alleviated to varying degrees,while the proportion of CD4+ T lymphocytes and CD4+/CD8+ ratio in spleen tissue of the positive control group and TCM high-dosage group increased,the proportion of CD8+ T lymphocytes decreased,the expression of T-bet mRNA in left lung and spleen tissues increased,and the expression of GATA-3 mRNA decreased,with statistical significance(P<0.05).Conclusion Guiqi Yiyuan Ointment can alleviate the lung and spleen injury of rats induced by 12C6+ beam radiation.Its mechanism is related to regulating the proportion of CD4+,CD8+ T lymphocytes and the expression of T-bet and GATA-3,and recovering cellular immune function.

ObjectiveTo explore the effects of Guiqi Yiyuan ointment combined with cisplatin on mice with Lewis lung cancer through the endoplasmic reticulum stress pathway and mitochondrial apoptosis pathway. MethodFifty SPF male C57BL/6 mice were randomly divided into the model group， cisplatin group （0.005 g·kg^-1）， and low， medium， and high dose groups of Guiqi Yiyuan ointment combined with cisplatin （0.005+1.6 g·kg^-1， 0.005+3.3 g·kg^-1， and 0.005+6.6 g·kg^-1）. Lewis cell suspension was inoculated under the axilla of mice in each group to construct the Lewis lung cancer xenograft mouse model. After continuous administration for 14 days， the mice were sacrificed. The body weight of the mice was measured， and the tumor weight was measured after the tumors were removed. The organ index and tumor inhibition rate were calculated. Hematoxylin-eosin （ HE） staining was used to observe the pathological changes in tumor tissue. Flow cytometry was used to detect the apoptosis rate of tumor cells and the ratio of reactive oxygen species （ROS）. Western blot was used to detect the expression of glucose-regulated protein 78 （GRP78）， phosphorylated activated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， activated transcription factor 4 （ATF4）， and apoptosis protein C/EBP homologous protein （CHOP） in the endoplasmic reticulum stress pathway， as well as cysteine aspartate protease-9 （Caspase-9）， B-cell lymphoma-2（Bcl-2）， and Bcl-2 associated X protein（Bax） in the mitochondrial apoptosis pathway. ResultCompared with those in the model group， the mice in the groups of Guiqi Yiyuan Ointment combined with cisplatin had shinier fur and better mental response status. Tumor mass was reduced in all treatment groups （P<0.05）， and tumor inhibition rate was increased in all treatment groups （P<0.05）. The thymus and spleen indices of the combined group were increased （P<0.05）， and obvious pathological changes were observed in the tumor tissue of all treatment groups， with a gradual decrease in heteromorphism. Destruction of massive tumor tissue was observed in the high-dose combined group， and the apoptosis rate and ROS generation rate of tumor cells were increased in all treatment groups （P<0.05）. The protein expression level of Bcl-2 in the tumor tissue gradually decreased （P<0.05）， while the protein expression levels of GRP78， p-PERK， ATF4， CHOP， Bax， and Caspase-9 were significantly increased （P<0.05）. Compared with the cisplatin group， tumor mass was reduced in the combined group （P<0.05）， and tumor inhibition rates in the low and high-dose combined groups were increased （P<0.05）. The thymus index， spleen index， apoptosis rate of tumor cells， and ROS ratio in the combined group were significantly increased （P<0.05）， while the protein expression levels of GRP78， p-PERK， Bax， and Caspase-9 were increased in the low and high-dose combined groups （P<0.05）. The protein expression levels of ATF4 and CHOP were increased in the combined group （P<0.05）， while the expression level of Bcl-2 protein gradually decreased （P<0.05）. ConclusionGuiqi Yiyuan ointment combined with cisplatin can exert anti-tumor effects in mice with Lewis lung cancer， reduce tumor mass， increase tumor inhibition rate， and induce apoptosis of lung cancer cells. Its mechanism may be related to the regulation of the endoplasmic reticulum stress pathway and mitochondrial apoptosis pathway.