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 retrospectively compare the clinical effects of the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the European Kidney Function Consortium (EKFC) equation based on creatinine to estimate glomerular filtration rate (eGFRcr) in a Chinese population.Methods:Patients and healthy individuals who visited the Zhongshan Hospital, Fudan University, between January 1, 2023, and December 31, 2023, were enrolled. The exclusion criteria were age<18 years, amputees, pregnant women, patients with muscle-related diseases, and patients who had undergone ultrafiltration or dialysis. The final study population included 660 078 individuals with a median age of 58 years (44, 68), 56.51% (372 987/660 078) of them were men. eGFRcr was calculated using the 2021 CKD-EPI, EKFC equations and initial 2009 CKD-EPI equation. Results were compared by differences (P 10), charges in population distribution and impact on staging of chronic kidney disease (CKD) by gender, age and creatinine results. Results:Compared with the results of 2009 and 2021 CKD-EPI eGFRcr, the P 10was 99.99% ( R 2=0.997). When applying the 2021 CKD-EPI eGFRcr equation, there was a slight overestimation of 3.77 (2.92, 4.47) ml/(min×1.73 m 2). 86.42% (570 455/660 078)participants had higher eGFRcr owing to the utilization of the 2021 CKD-EPI equation, which did not cause CKD stage change. A total of 12.35% (81 514/660 078) of subjects had different CKD stage with the higher 2021 CKD-EPI eGFRcr. 1.23% (8 109/660 078) had lower eGFRcr but no change in the CKD stage with the 2021 equation. Compared to the 2009 CKD-EPI eGFRcr results, the EKFC eGFRcr demonstrates P 10 values of 89.79%, with a correlation coefficient of R 2=0.976. The overall eGFRcr values using the EKFC equation were decreased by 4.63(-2.22, -7.04) ml/(min×1.73 m 2). There were 75.14% (495 992/660 078) individuals whose eGFRcr results were lower in EKFC equation, which did not cause CKD stage change. There were 15.63% (103 161/660 078) leading to a different CKD stage. Additionally, 8.80% (58 077/660 078) individuals with a higer eGFRcr result did not change CKD stage, while 0.43% (2 848/660 078) experienced a change in CKD staging due to the overestimation. Conclusions:Compared with the 2009 CKD-EPI eGFRcr results, the 2021 CKD-EPI eGFRcr results were slightly higher and had good consistency in different genders and ages. However, the EKFC eGFRcr was generally lower than 2009 CKD-EPI eGFRcr, showing poor consistency. The differences between eGFR equations should be considered when judging the CKD stage of patients.

Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high hetero-geneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell prolif-eration,differentiation,and disease progression.Significant associations between tumor grade,prog-nosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.

Objective:To learn about the single nucleotide polymorphism (SNP) population structure and regional distribution characteristics of Yersinia pestis in the natural focus of plague in Qinghai-Tibet Plateau. Methods:A total of 319 representative strains of Yersinia pestis isolated from natural focus of plague in Qinghai-Tibet Plateau from 1954 to 2020 were selected, and 2 298 SNP loci included in the global Yersinia pestis phylogenetic tree were compared by whole genome sequencing technology. MEGA 6.0 software was used to construct phylogenetic trees of 319 strains of Yersinia pestis from Qinghai-Tibet Plateau, determine the SNP population structure of Yersinia pestis in the focus, and describe its regional distribution characteristics. Results:The 319 strains of Yersinia pestis isolated from Qinghai-Tibet Plateau natural plague foci were distributed in 5 clades, namely 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED. The 1.IN clade contained 209 strains (65.52%, 209/319), which was the dominant population of strains in Qinghai Province, accounting for 90.51% (143/158). The 2.ANT clade contained 83 strains (26.02%, 83/319), which was the dominant population in Tibet Autonomous Region, accounting for 67.24% (78/116). The 3.ANT, 0.PE, and 2.MED clades contained 12 (3.76%, 12/319), 9 (2.82%, 9/319) and 6 strains (1.88%, 6/319), respectively, which were scattered in Qinghai Province, Gansu Province, Sichuan Province, Tibet Autonomous Region, and Xinjiang Uygur Autonomous Region under the jurisdiction of Qinghai-Tibet Plateau. Conclusion:The SNP population structure of Yersinia pestis in natural focus of plague in Qinghai-Tibet Plateau is relatively rich, and the strains are distributed in 5 clades: 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED, showing the distribution characteristics of specific regions.

Objectives:To investigate the prognostic value of soluble growth stimulation expressed gene 2 protein(sST2)combined with N-terminal pro-brain natriuretic peptide(NT-proBNP)in patients with ST-segment elevation myocardial infarction(STEMI)undergoing primary percutaneous coronary intervention(PCI). Methods:A total of 206 patients who were diagnosed with STEMI for the first time and underwent emergency PCI from August 2020 to February 2021 in the People's Hospital of Liaoning Province were enrolled.Patients were followed up for 3 years and divided into major adverse cardiac event(MACE,a composite endpoint event including cardiac death,stroke,heart failure,and ischemia-driven revascularization)group and MACE-free group.Multivariate cox analysis was performed to determine the independent risk factors for the prognosis of primary PCI in STEMI patients;the predictive value of sST2 and NT-proBNP for the occurrence of MACE in STEMI patients undergoing primary PCI was assessed by ROC analysis and the prediction of MACE by each factor by itself and the combined variables was analyzed with the Delong test. Results:There were 62 cases of MACE during the 3-year follow-up.Compared with the MACE-free group,patients in the MACE group had higher levels of sST2 and NT-proBNP,higher proportion of patients with left anterior descending branch lesions,anterior wall myocardial infarction,lower LVEF,and higher proportion of coronary artery slow flow(all P<0.05).Multivariate Cox analysis showed that sST2(HR=1.018,95%CI:1.012-1.024,P<0.001)and NT-proBNP(HR=1.001,95%CI:1.000-1.010,P<0.001)were independent predictors of MACE.According to the statistical analysis of ROC and Delong test,the AUC of combined sST2 and NT-proBNP in predicting MACE was 0.854,the sensitivity was 64.5%,the specificity was 93.1%,and the combined prediction of prognosis was better than that of individual prediction,with statistically significant difference(Z=2.119,P=0.034;Z=2.178,P=0.029). Conclusions:Serum sST2 and NT-proBNP are valuable predictors of MACE after emergency PCI in patients with STEMI,and the predictive efficacy increases with combined assessment of both sST2 and NT-proBNP.

Objectives:To explore the feasibility of using hemodynamic phenotypes to guide antihypertensive treatment medication. Methods:This study prospectively included 100 hypertensive patients who received outpatient treatment at Haidian Hospital in Beijing from January 2021 to December 2021.Evaluation of blood pressure was conducted using laboratory and home blood pressure measurements,impedance cardiogram(ICG)detection was performed.Following hemodynamic phenotypes and therapeutic phenotypes were established:hyperkinetic phenotype(increased heart rate)using β-blockers,large artery phenotype(increased large artery resistance index)using calcium antagonists,peripheral vascular phenotype(increased peripheral vascular resistance index)using renin angiotensin system inhibitors,and high-volume phenotype(increased blood volume saturation)using diuretics.Patients were randomly divided into ICG group(n=50,medication treatment based on hemodynamic characteristics)and control group(n=50,treatment based on hypertension guidelines and clinical experience).Patients were followed up for 8 weeks and the blood pressure reduction amplitude and compliance rate were compare between the two groups. Results:There was no statistically significant difference in baseline data such as sex,age,height,weight,and hemodynamic parameters between the two groups(all P＞0.05).There was no statistically significant difference in the types of baseline medication between the two groups(P＞0.05).After medication adjustment,the types of medication increased,but the difference between the two groups was still not statistically significant(P＞0.05).Clinic blood pressure:After 8 weeks,decreases in systolic([8.38±27.78]mmHg,1 mmHg=0.133 kPa)and diastolic([3.94±18.15]mmHg)blood pressure were greater in the ICG group as compared to the control group(both P＜0.05).The blood pressure compliance rate(＜140/90 mmHg)was higher in the ICG group than that in the control group(66.0%vs.42.0%,P＜0.05).Family blood pressure:after 8 weeks,the reduction in systolic([8.22±21.31]mmHg,P＜0.01)and diastolic([4.76±13.88]mmHg,P＜0.05)blood pressure was greater in the ICG group compared to the control group.The blood pressure compliance rate(＜135/85 mmHg)was higher in the ICG group than that in the control group(70.0%vs.48.0%,P＜0.05).Changes in corresponding hemodynamic parameters before and after two different antihypertensive drugs:the heart rate,arterial resistance index,peripheral vascular resistance index,and blood volume saturation of the ICG group all significantly decreased compared to baseline(all P＜0.05).The control group showed a significant decrease in peripheral vascular resistance index compared to baseline(P＜0.05),while there was no statistically significant difference in heart rate,large artery resistance index,and blood volume saturation compared to baseline(all P＞0.05). Conclusions:By using impedance cardiogram to assess hemodynamic phenotypes and accurately guide the selection of antihypertensive drugs based on hemodynamic phenotypes,it is possible to more effectively lower blood pressure and improve blood pressure compliance.