Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

Reactive oxygen species (ROS) are major contributors to radiation therapy-induced side effects in cancer patients. A fusion antioxidant enzyme comprising glutathione S-transferase (GST), superoxide dismutase 1 (SOD1), and a transmembrane peptide has been shown to effectively mitigate ROS-induced damage. To enhance its targeting capability, the fusion protein was further modified by incorporating a matrix metalloproteinase-2/9 substrate peptide (X) and the transmembrane peptide R9, yielding the antioxidant enzyme GST-SOD1-X-R9 (GS1XR). This modification reduced its transmembrane ability in tumor cells, thereby selectively protecting normal cells from oxidative stress. However, the use of non-human GST poses potential immunogenicity risks. In this study, we employed seamless cloning technology to construct an expression vector containing the human GST gene to replace the non-human GST gene, and then expressed and purified novel fusion antioxidant enzymes GS1R and GS1XR. The protective effects of newly constructed GS1R and GS1XR against hydrogen peroxide (H₂O₂)-induced oxidative damage in L-02 cells were then evaluated using GS1 as a control. Enzymatic activity assays revealed that the specific activity of GST in GS1XR remained unchanged compared to the unmodified protein, while SOD activity was enhanced. Exposure to 200 μmol/L H₂O₂ transiently activated the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway; however, this activation diminished after 24 h, reducing cell viability to 48.4%. Both GS1R and GS1XR effectively scavenged intracellular ROS, directly counteracting oxidative stress and promoting Nrf2 nuclear translocation, thereby activating antioxidant pathways and restoring cell viability to normal levels. The two enzymes showed comparable efficacy. In contrast, GS1, lacking transmembrane capability, was restricted to scavenging extracellular ROS and provided only limited protection. In conclusion, both novel fusion antioxidant enzymes demonstrated significant potential in safeguarding normal cells from ROS-mediated oxidative damage. The findings provide a foundation for further investigation in related field.
Humans ; Oxidative Stress/drug effects* ; Hydrogen Peroxide ; Antioxidants/metabolism* ; Glutathione Transferase/metabolism* ; Recombinant Fusion Proteins/pharmacology* ; Superoxide Dismutase-1 ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase/biosynthesis*

BACKGROUND:Nowadays,there are increasing reports on the digitization and visualization system of acupuncture points for adults in traditional Chinese medicine,and the digitization and visualization system of acupuncture points for children in traditional Chinese medicine and the simulation system of acupuncture manipulation for Mongolian medicine training have been reported.However,there are no reports on relevant systems for children in Mongolian medicine. OBJECTIVE:To develop a simulation system of acupuncture points for children in Mongolian medicine,in the hope that it can be used for clinical teaching,manipulation practice and research on acupuncture safety. METHODS:Based on the tomographic anatomical dataset of preschool boys,a three-dimensional(3D)digital virtual anatomical model of children with multiple internal organs and tissues was constructed by using PhotoShop.2021 and Digihuman Reconstruction System software.The relevant annotation information database of 27 acupoints such as Dinghui acupoint of Mongolian medicine was compiled by the Unity database language.The Mongolian gold needle and silver needle were selected to record the acupuncture point teaching video on the 3D printed head and neck resin model of children.In Unity3D software,children's anatomical model,acupoint annotation information database and acupuncture operation video were integrated and coded,and a 3D digital children's Mongolian acupuncture acupoint visualization system integrating simulation acupuncture training,clinical teaching and acupuncture safety research was successfully created. RESULTS AND CONCLUSION:This study was based on real children's specimens.In order to reduce the error of two-dimensional segmentation,the manual layer-by-layer segmentation section image method was used to ensure the accuracy of the 3D model to the greatest extent.The Digihuman Reconstruction System was used to extract and save the individual segmentation data while maximizing the accuracy of the 3D model.PhotoShop.2021 software was used to complete the 3D reconstruction of the outer skin of the head and neck of children and the internal bony structure,cervical spinal cord,blood vessels and nerves,muscles and ligaments.After 3D reconstruction,the basic morphology of each independent structure and the integrity of the overall contour were verified in MeshLab software and the final fine adjustment and anatomical position confirmation were conducted using 3-matic research 13.0 software.The real anatomical morphology of the head and neck of preschool children was successfully simulated and restored.Unity3D software was used to integrate the 3D model of children,acupuncture operation video and acupoint annotation database,and the 3D digital Mongolian acupuncture acupoint visualization system for children was successfully constructed.Based on the real continuous fault ultra-thin dataset of preschool boys in China,China's first 3D digitization and visualization system of acupuncture points in the head and neck of children in Mongolian medicine was developed.Compared with the previous acupuncture soft works,this system is more suitable for the anatomical morphological development characteristics of Asian children,and has a high value of application in the fields of research on the safety of acupuncture in Mongolian medicine,clinical teaching and acupuncture simulation training.

Objective: To investigate the molecular mechanism and identify potential drugs for subthreshold depression (SD), and elucidate the detalied mechanism of Danzhi Xiaoyao powder (DZXY) in SD. Methods: Using RNA-sequencing, we identified differentially expressed genes (DEGs) in leukocytes of SD compared to healthy controls, deciphered their functions and pathways, and identified the hub genes of SD. We also assessed changes in leukocyte transcription factor activity in patients with SD using the TELiS platform. The Connectivity Map database was retrieved to screen candidate drugs for SD. Based on network pharmacology, we elucidated the “multi-component, multi-target, and multi-pathway” mechanism of DZXY in the treatment of SD. Results: We identified 1080 DEGs (padj <0.05 and |log2 (fold change)| ≥ 1 & protein coding) in the leukocytes of patients with SD. These DEGs, including hub genes, were primarily involved in immune and inflammatory response-related processes. Transcription factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune cells. Connectivity Map analysis identified 28 potential drugs for SD treatment, particularly SB-202190 and TWS-119. Constructing the “Direct Compounds-Direct Targets-Pathways” network for DZXY and SD revealed the curative mechanisms of DZXY in SD, primarily including inflammatory response, lipid metabolism, immune response, and other processes. Conclusion These results provide new insights into the characteristics and functional changes of leukocytes in SD, partially illustrate the pathogenesis of SD, and suggest potential drugs for SD. The curative mechanisms of DZXY in SD are also partially elucidated.

Objective To explore the characteristics of TCM in the treatment of asymptomatic hyperuricemia based on data mining.Methods Clinical literature on the TCM treatment of asymptomatic hyperuricemia in CNKI,Wanfang Data,VIP and SinoMed was retrieved.After screening,the prescriptions obtained were input into Excel 2019 database,and SPSS Modeler 18.0,SPSS Statistics 26.0 and Cytoscape 3.9.1 were used for frequency analysis,association rule analysis,clustering analysis and factor analysis.Results A total of 133 articles meeting the criteria were included,and 140 prescriptions were included,involving 202 kinds of Chinese materia medica,with a total frequency of 1 387 times.22 drugs,such as Smilacis Glabrae Rhizoma,Coicis Semen,Dioscoreae Spongiosae Rhizoma,Astrctylodis Rhizoma,were frequently used in the treatment of asymptomatic hyperuricemia.The commonly used drugs were drugs for urine excretion to strain off dampness,tonics,clearing heat,promoting blood circulation and removing blood stasis.The medicinal property was mainly warm,the medicinal taste was mainly sweet,and the meridians were mainly liver,spleen,stomach and kidney meridians.21 groups of medicinal combinations were obtained by high frequency drug association rule analysis,among which the core drug pairs were Coicis Semen-Astrctylodis Rhizoma,Smilacis Glabrae Rhizoma-Dioscoreae Spongiosae Rhizoma-Coicis Semen,Coicis Semen-Astrctylodis Rhizoma-Smilacis Glabrae Rhizoma,etc.Clustering analysis obtained 5 clustering methods,and factor analysis obtained 7 common factors.Conclusion In the TCM treatment of asymptomatic hyperuricemia,the main methods are urine excretion to strain off dampness,strengthening spleen and tonifying qi,and the main drugs are Smilacis Glabrae Rhizoma,Coicis Semen,Dioscoreae Spongiosae Rhizoma,Astrctylodis Rhizoma,which can provide reference for clinical treatment of asymptomatic hyperuricemia.

Objective To explore the characteristics of TCM prescriptions for acute gouty arthritis based on data mining methods;To provide reference for clinical treatment.Methods The clinical literature on the TCM treatment of acute gouty arthritis was retrieved from CNKI,Wanfang Data,VIP and SinoMed.The obtained formulas were input into Excel 2019 to establish a database,and SPSS Modeler 18.0,SPSS Statistics 26.0 and Cytoscape 3.9.1 were used for frequency analysis,association rule analysis,clustering analysis and factor analysis.Results A total of 290 articles meeting the requirements were included,including 295 prescriptions,involving 218 kinds of Chinese materia medica,with a total frequency of 3 573 times.24 kinds of Chinese materia medica,including Coicis Semen,Phellodendri Chinensis Cortex,Atractylodis Rhizoma,Smilacis Glabrae Rhizoma,Dioscoreae Spongiosae Rhizoma,Glycyrrhizae Radix et Rhizoma,Achyranthis Bidentatae Radix were used frequently in the treatment of acute gouty arthritis.The commonly used drugs were heat-clearing drugs,moisture-clearing drugs,blood circulation-activating drugs for removing blood stasis,and wind-dampness drugs.The property was mainly cold,the taste was mainly bitter,and the meridians were mainly liver,stomach,spleen and kidney meridians.The analysis of high-frequency drug association rules obtained 22 drug combinations,among which the core drug pairs were Phellodendri Chinensis Cortex-Atractylodis Rhizoma,Coicis Semen-Atractylodis Rhizoma-Phellodendri Chinensis Cortex.Clustering analysis obtained 4 clustering methods,and factor analysis obtained 9 common factors.Conclusion The main treatment of acute gouty arthritis by TCM is clearing heat and dampness,removing blood stasis and clearing collaterals,tonifying liver and kidney,regulating spleen and stomach,which could provide reference for the clinical treatment of acute gouty arthritis.

Objective To analyze and summarize the clinical presentation of spontaneous and secondary intracranial hypotension syndrome(IHS).Methods Patients diagnosed with spontaneous or secondary IHS from September 2022 to May 2023 were retrospectively analyzed.The clinical data,imaging features,treatment methods and prognosis were collected.The correlation between intracranial pressure values and clinical characteristics of the patients was statistically analyzed.Results A total of 30 patients were enrolled,and the proportion of spontaneous and secondary IHS was 63%(19 cases)and 37%(11 cases),respectively.In terms of clinical features,orthostatic headache was the most common type(29 cases,96.7%)and most commonly involved occipital region(12 cases,40.0%),followed by frontoparietal region(9 cases,30.0%).Among the brain imaging features,dural enhancement was the most common(17 cases,56.7%).According to CT angiography of spinal cord findings,cerebrospinal fluid leakage is one of the most common location of cervical spine segments(10 cases),and on the thoracic segments(9 cases),followed by the thoracic segments(4 cases)and lumbar segments(4 cases).After conservative treatment and surgical treatment,the total effective rate was 90%.Conclusion Orthostatic headache and cranial MRI"dural enhancement"have strong indication on the definitive diagnosis of IHS.CT myelography is helpful to precisely localize the site of cerebrospinal fluid leakage.Targeted epidural blood patch therapy is an effective method to cure IHS when conservative treatment is ineffective.

Objective:To investigate the value of artificial intelligence (AI) cytomorphologic analysis system in the cytomorphological diagnosis and therapeutic evaluation of acute myeloid leukemia (AML).Methods:Bone marrow smear samples were collected from 150 patients with newly diagnosed and treated acute myeloid leukemia who were inpatients and outpatients at the Department of Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from June 1, 2021 to July 31, 2022 for retrospective analysis. Among them, there were 50 patients in the newly diagnosed group, including 28 males and 22 females, with the onset age of 43.5(32.3,58.8)years. There were 100 patients in the post-treatment group, including 36 males and 64 females, with the onset age of 34.5(23.0,47.0)years. The results from cytomorphology expert were used as the gold standard and the Python 3.6.7 was used for analysis to evaluate the accuracy, sensitivity, and specificity of the AI cytomorphologic analysis system for blast cell recognition in AML diagnosis and treatment.Results:The proportion of blasts in AI analysis of 50 samples in the newly diagnosed group was≥20%, which met the diagnostic criteria of AML. AI analysis of blasts had an accuracy of 90.3%, sensitivity of 85.5%, and specificity of 98.0%. The correlation coefficient between AI and the proportion of blasts analyzed by experts was positively correlated( r=0.882, P<0.001). Meanwhile, in the post-treatment group, the sensitivity and specificity of AI analysis of blasts were 89.7% and 99.2%, respectively. The correlation coefficient between AI and the proportion of blasts analyzed by experts was positively correlated( r=0.957, P<0.001). According to AI analysis data, there are 8 samples in this group whose AI efficacy evaluation results on AML are inconsistent with expert analysis. Conclusion:AI cytomorphologic analysis system has high accuracy, sensitivity and specificity for blast cell recognition in AML morphological diagnosis and therapeutic evaluation.

ObjectiveTo investigate the mechanism of Xumingtang in Gu Jin Lu Yan （《古今录验》） in regulating cell pyroptosis through the hypoxia-inducible factor-1α （HIF-1α）/NOD-like receptor pyrin domain-containing protein 3 （NLRP3） pathway in ischemic stroke （IS）. MethodSD rats were randomly divided into a sham operation group， a model group， low- and high-dose Xumingtang groups， and a metformin group， with 20 rats in each group. Oral administration was performed for 3 days， and tissue samples were collected. Differential messenger RNA （mRNA） was screened using high-throughput sequencing， and Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analyses were performed on key differentially expressed genes. The modified neurological severity score （mNSS） and 2，3，5-triphenyltetrazolium chloride （TTC） staining were used to evaluate the effect of brain infarction. Hematoxylin-eosin （HE） staining was used for pathological morphological observation of brain tissue. Enzyme-linked immunosorbent assay （ELISA） was used to compare the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in the ischemic cortical region. Double staining immunohistochemistry was used to detect the co-localization of HIF-1α and NLRP3. Real-time quantitative polymerase chain reaction （PCR） was performed to detect the mRNA expression of NLRP3， HIF-1α， Caspase-1 （CASP-1）， and gasdermin D （GSDMD）. Western blot was used to detect the protein expression of HIF-1α， NLRP3， CASP-1， and GSDMD. ResultA total of 5 705 differentially expressed genes （2 733 downregulated and 2 972 upregulated） were obtained by mRNA sequencing. After conversion to homologous genes and intersection with the pyroptosis gene set， 95 key differentially expressed pyroptosis genes were obtained. Compared with the sham operation group， the model group showed significantly increased mNSS scores， larger brain infarction areas （P<0.01）， diverse neuronal morphology， disordered arrangement， widened cell gaps， significantly increased levels of IL-1β and IL-18 in the ischemic cortical region （P<0.01）， enhanced co-localization fluorescence intensity， and significantly increased mRNA and protein expression levels of HIF-1α， NLRP3， CASP-1， and GSDMD （P<0.01）. Compared with the model group， the high-dose Xumingtang group showed the most significant improvement in neurological function scores and brain infarction areas （P<0.01）. The neuronal integrity and arrangement were more complete， and the cell gaps were narrower in all groups with drug treatment， with significantly reduced co-localization fluorescence intensity. Xumingtang could reduce the levels of IL-1β， IL-18， and the mRNA and protein expression of HIF-1α， NLRP3， CASP-1， and GSDMD （P<0.05， P<0.01）， with the high-dose Xumingtang group showing the most significant effect （P<0.01）. ConclusionXumingtang in Gu Jin Lu Yan can inhibit cell pyroptosis and promote neurological function recovery after IS， which may be related to the inhibition of the HIF-1α/NLRP3 pathway.

Objective:To analyze the external quality control assessment results of urinary iodine, salt iodine and water iodine in iodine deficiency disorders laboratories in Qinghai Province, to evaluate the testing capacity of provincial, municipal and county-level laboratories and the operation of external quality control network, so as to provide quality assurance for consolidating and eliminating iodine deficiency disorders.Methods:In 2021, 1 provincial, 8 municipal, and 43 county-level laboratories in Qinghai Province had participated in the assessment of urinary iodine and salt iodine, while 1 provincial and 8 municipal-level laboratories had participated in the assessment of water iodine. The assessment results were evaluated using the method of reference value ± uncertainty of external quality control samples.Results:All laboratories that participated in the assessment had provided feedback. One provincial-level laboratory passed the assessment of urinary iodine, salt iodine, and water iodine. Among 8 municipal-level laboratories, 2 laboratories failed the urinary iodine assessment, with a pass rate of 6/8; the assessment of salt iodine and water iodine in 8 laboratories were all qualified. Among 43 county-level laboratories, 7 laboratories failed the urinary iodine assessment, with a pass rate of 83.7% (36/43); the assessment of salt iodine in 43 laboratories were all qualified.Conclusions:The external quality control network of iodine deficiency disorders laboratories in Qinghai Province has fully covered all municipal and county-level laboratories. The testing capability of provincial-level laboratory is stable and maintains a high level; the testing quality of some municipal and county-level laboratories is still unstable and needs to be further strengthened.