OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

OBJECTIVE: To propose a machine learning-based method for predicting the trajectories during manual acupuncture manipulation (MAM), aiming to improve the precision and consistency of acupuncture practitioner' operation and provide the real-time suggestions on MAM error correction. METHODS: Computer vision technology was used to analyze the hand micromotion when holding needle during acupuncture, and provide a three-dimensional coordinate description method of the index finger joints of the holding hand. Focusing on the 4 typical motions of MAM, a machine learning-based MAM trajectory predictive model was designed. By integrating the changes of phalangeal joint angle and hand skeletal information of acupuncture practitioner, the motion trajectory of the index finger joint was predicted accurately. Besides, the roles of machine learning-based MAM trajectory predictive model in the skill transmission of acupuncture manipulation were verified by stratified randomized controlled trial. RESULTS: The performance of MAM trajectory predictive model, based on the long short-term memory network (LSTM), obtained the highest stability and precision, up to 98%. The learning effect was improved when the model applied to the skill transmission of acupuncture manipulation. CONCLUSION The machine learning-based MAM predictive model provides acupuncture practitioner with precise action prediction and feedback. It is valuable and significant for the inheritance and error correction of manual operation of acupuncture.
Humans ; Acupuncture Therapy/instrumentation* ; Machine Learning ; Adult ; Male ; Female

OBJECTIVE: To investigate the effect of manual acupuncture manipulations (MAMs) on subcutaneous muscle tissue, by developing quantitative models of "lifting and thrusting" and "twisting and rotating", based on machine learning techniques. METHODS: A depth camera was used to capture the acupuncture operator's hand movements during "lifting and thrusting" and "twisting and rotating" of needle. Simultaneously, the ultrasound imaging was employed to record the muscle tissue responses of the participants. Amplitude and angular features were extracted from the movement data of operators, and muscle fascicle slope features were derived from the data of ultrasound images. The dynamic time warping barycenter averaging algorithm was adopted to align the dual-source data. Various machine learning techniques were applied to build quantitative models, and the performance of each model was compared. The most optimal model was further analyzed for its interpretability. RESULTS: Among the quantitative models built for the two types of MAMs, the random forest model demonstrated the best performance. For the quantitative model of the "lifting and thrusting" technique, the coefficient of determination (R²) was 0.825. For the "twisting and rotating" technique, R² reached 0.872. CONCLUSION Machine learning can be used to effectively develop the models and quantify the effects of MAMs on subcutaneous muscle tissue. It provides a new perspective to understand the mechanism of acupuncture therapy and lays a foundation for optimizing acupuncture technology and designing personalized treatment regimen in the future.
Humans ; Acupuncture Therapy/methods* ; Machine Learning ; Male ; Adult ; Female ; Subcutaneous Tissue/diagnostic imaging* ; Young Adult

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective To explore the use of indirect methods to establish a reference interval for serum car-bohydrate antigen 242(CA242)in adults in Shanghai and to validate it.Methods A total of 51 897 cases of CA242 testing data from the laboratory information management system of the Department of Clinical Labo-ratory at the hospital from August 2022 to July 2023 were collected.After data cleaning and normal transfor-mation,the Turkey method was used to remove outliers,and 19 653 cases of data were finally included in the study.Then,the Hoffmann method was used to establish the P95 reference interval for serum CA242.The study selected 691 apparently healthy individuals from January to March 2024 to validate the self built refer-ence interval for CA242.The physical examination population with the reference interval recommended by the reagent instructions≤CA242 value

Objective To explore the correlation between the pathogenesis of toxins damaging liver collateral and the incidence of type 2 diabetes mellitus(T2DM)based on the theory of five circuits and six qi.Methods A total of 986 patients with T2DM treated in the Department of Endocrinology and Metabolism at the Affiliated Hospital of Changchun University of Chinese Medicine from February 2019 to October 2023 were selected as the study subjects.The influences of circuit and qi indicators in the theory of five circuits and six qi on the constitutional characteristics of T2DM patients and the role of pathogenesis of toxins damaging liver collateral in the incidence of T2DM were investigated.Results(1)The five-circuit and six-qi analysis showed that the yearly circuit and sitian/zaiquan conditions had no significant effect on the constitutional characteristics of patients with T2DM(P＞0.05).However,dominant circuit,guest circuit,dominant qi and guest qi significantly influenced the constitutional characteristics of patients with T2DM(P＜0.05).For the distribution of circuit-qi indicators at birth among the 986 patients,dominant circuit was predominated by the terminal circuit of taiyang cold-water,guest circuit was characterized by deficient wood circuit or excessive water circuit,dominant qi was predominated by yangming dry-metal,and guest qi was characterized by taiyin damp-earth.(2)The correlation between the pathogenesis of toxins damaging liver collateral and the incidence of T2DM through comparative analysis revealed that the conveying and dispersing function of the liver plays a leading role in maintaining the body's yin-yang balance and ensuring free movement of qi,indicating that the critical role of toxins damaging liver collateral is the key to the incidence of diabetes.Conclusion Circuit-qi indicators have a certain influence on the constitutional characteristics of T2DM patients.The circuit-qi features at birth of the individuals prone to T2DM are as follows:dominant circuit predominated by the terminal circuit of taiyang cold-water,guest circuit characterized by deficient wood circuit or excessive water circuit,dominant qi being yangming dry-metal,and guest qi being taiyin damp-earth.Pathogenesis of toxins damaging liver collateral is closely related to the incidence of T2DM.Therefore,in treatment,the regulatory role of the liver should be emphasized,and liver-soothing herbs should be used based on syndrome differentiation,aiming for holistic treatment of the physique and the spirit and enhancing the therapeutic efficacy.The exploration will provide a new perspective and approach for the treatment of T2DM.

Objective To evaluate the gap between China's top-tier medical institutions and top-tier international medical institutions,and to provide references for the construction of first-class medical science discipline in China.Methods Using globally recognized rankings of medical institutions,we selected 24 top-tier international medical institutions and 11 top-tier Chinese medical institutions.Publicly available,general,and comparable data on indicators were collected to analyze the performance and gaps between top-tier international and Chinese medical institutions in human resources development,talent cultivation,scientific research,social services,and discipline construction.Results In the field of medicine,the largest gap between top-tier international and Chinese medical institutions was in high-level talent.Specifically,the average numbers of individuals who are Clarivate Analytics'Highly Cited Researchers,who are Nobel Prize laureates in Physiology or Medicine,and who serve on advisory boards or editorial boards of top medical journals,and who rank among the Top 2 000 Medicine Scientists were 1.00,0.09,0.45 and 4.00,respectively,among top-tier Chinese medical institutions,while those of the top-tier international medical institutions were 131.46,118.25,9.72,and 6.76 times,respectively,those of the Chinese medical institutions.The second largest gap was in social services and medical innovation.The average proportion of industrial collaboration papers and the number of clinical trials of China's top-tier medical institutions were 1.51％and 1 851,respectively,while those of international top-tier medical institutions were 3.62 and 1.87,times,respectively,those of top-tier Chinese medical institutions.However,the average number of(untranslated)patents held by top-tier international medical institutions was only 15％ of that of China's top-tier medical institutions.The third largest gap was in scientific research.The average number of papers published in New England Journal of Medicine,Journal of the American Medical Association,The Lancet,and British Medical Journal,the percentage of hot papers in papers included in Web of Science,the percentage of highly cited papers,the percentage of international collaboration papers,the total number of citations per paper,category normalized citation impact(CNCI),and the number of publications of top-tier Chinese medical institutions were 78,0.03％,1.39％,22.55％,19.61,1.26,30 706,while those of the top-tier international medical institutions were 6.96,2.66,2.57,2.15,1.83,1.58 and 1.54 times those of the Chinese medical institutions,respectively.However the average percentage of zero-citation papers of top-tier international medical institutions was only 71％of that of China's top-tier medical institutions.Furthermore,in discipline development,the average overall scores of the Times Higher Education(THE)and QS rankings for medicine-related disciplines of top-tier Chinese medical institutions were 72.84 and 69.30,respectively,while those of top-tier international medical institutions were 1.38 and 1.21 times those of the Chinese medical institutions.However,in terms of talent cultivation,the average number of students of China's top-tier medical institutions was 10724,which is roughly double that of international institutions.Conclusion Currently,China's top-tier medical institutions are still in a basic stage that emphasizes the quality of talent cultivation and medical services.There is considerable room for development and potential for catching up in multiple aspects,especially in high-level talent,medical research,and innovation.It is recommended that the construction experience of top-tier international medical institutions should be fully utilized to build China's first-class medical science discipline.

Objective To analyze the clinical characteristics of mycoplasma pneumoniae pneumonia(MPP)in children with atopic constitution and exploring the predictors of disease conditions.Methods A total of 250 children diagnosed with MPP in the Department of Pediatric Respiratory Medicine,Xinhua Hospital,Shanghai Jiaotong University School of Medicine from September 2019 to September 2022 were selected and divided into atopic group(n=149)and non-atopic group(n=101)according to whether they were atopic,to explore the clinical characteristics of MPP in children with atopic constitution and the risk factors of severe mycoplasma pneumoniae pneu-monia(SMPP).The efficacy of the combined test of lactate dehydrogenase(LDH),immunoglobulin E(IgE)and serum amyloid A(SAA)in predicting the development of SMPP in MPP children with atopic constitution was evaluated by the receiver operating character-istic(ROC)curve.Results Children in the atopic group had more pronounced symptoms of cough,wheezing,nasal congestion,croup,combined pleural effusion with severe pneumonia and the proportion requiring hormone therapy than those in the non-atopic group,and the differences were statistically significant(P＜0.05).Logistic regression analysis showed that serum IgE,SAA and LDH levels were in-dependent risk factors for the development of SMPP in MPP children with atopic constitution(P＜0.05);ROC curve analysis showed that the combined test of IgE,LDH and SAA could be used to predict the development of SMPP in MPP children with atopic constitution,with an area under the curve(AUC)of 0.881,sensitivity of 81.0％,and specificity of 85.0％.Conclusion MPP children with atopic con-stitution are more likely to develop SMPP and require hormone therapy.The combined detection of serum IgE,SAA and LDH can effec-tively predict the occurrence of SMPP in MPP children with atopic constitution.

Objective To investigate the efficacy and safety of sacubitril valsartan in the treatment of heart failure(HF)of midrange ejection fraction(HFmrEF)in patients after acute myocardial infarction(AMI).Methods A total of 102 patients with HFmrEF after AMI were divided into the control group and the experimental group,with 51 cases in each group.The control group was given conventional treatment for AMI and anti-HF treatment,and the angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)was used without contraindications.The experimental group was replaced by ACEI/ARB with sacubitril valsartan on the basis of the control group.After 6 months of treatment,the total effective rates of the two groups after treatment were analyzed,and the cardiac function,N-terminal pro-brain natriuretic peptide(NT-proBNP)and serum inflammatory factor C-reactive protein(CRP)were compared before and after treatment.The occurrence of adverse reactions after treatment was recorded.Kaplan-Meier method was used to analyze the cumulative cardiovascular mortality,HF rehospitalization rate and end-event-free survival after 6 months of treatment in two groups.Results After treatment,there was no significant difference in the occurrence of adverse reactions between the two groups(P>0.05).The total effective rate was higher in the experimental group than that of the control group(P<0.05).Compared with before treatment,left ventricular ejection fraction(LVEF),stroke volume(SV),mitral diastolic blood flow velocity E peak and A peak ratio(E/A)and 6 min walking distance(6MWD)were increased in the two groups,and left ventricular end-diastolic diameter(LVEDD)and left atrial diameter(LAD)were decreased in the two groups after treatment(all P<0.05).After treatment,LVEF,SV,E/A and 6MWD were higher in the experimental group than those in the control group(P<0.05).LVEDD and LAD were lower than those in the control group(all P<0.05).Compared with results before treatment,NT-proBNP and CRP were decreased after treatment in the experiment group than those in the control group(P<0.05).There was no significant difference in the cumulative cardiovascular mortality between the experiment group and the control group(3.9％vs.5.9％,P=0.524).The cumulative HF rehospitalization rate was lower in the experimental group than that of the control group(9.8％vs.23.5％,P=0.042).The cumulative end-point-free survival rate was higher in the experiment group than that of the control group(86.3％vs.70.6％,P=0.037).Conclusion Sacubitril valsartan is safer and more effective than ACEI/ARB in the treatment of AMI patients with HFmrEF,and it is worthy of clinical promotion.