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 effect of urine mixing degree on 24-hour urinary total protein(24 h UTP)in patients with chronic kidney disease(CKD).Methods From October 1,2023 to December 31,2023,30 hospitalized patients who needed to complete 24 h UTP testing in Zhongshan Hospital,Fudan University were selected.A 5 L unified container was used to collect urine for 24 hours.After collection and one hour's standing,the urine sample was divided into upper,middle,and lower equal parts according to volume,which was defined as direct-sampling group.Then,the urine samples were fully mixed with a magnetic stirrer and sampled again according to the above-mentioned three-equal sampling method,which was defined as mixed-sampling group.The generalized estimating equation was used to compare the urinary protein concentration before and after mixing and at different sampling location.Results The results of generalized estimating equation showed that after controlling the variable"sampling position",there was no significant difference in urinary protein concentration between the direct-sampling group and the mixed-sampling group.After controlling the variable"mixing method",there was still no significant difference in urinary protein concentration at different sampling positions.After adjusting the covariates such as age,gender,and estimated glomerular filtration rate(eGFR),the results were consistent.Conclusions With standard protocol,the entire 24-hour urine sample is a relatively even-distributed solution.After the total urine collection is completed,the temporary sample can be directly extracted from any level of the original urine within 1 hour,and the urine protein concentration of the sample multiplied by the urine volume can reflect the 24 h UTR.

Objective To evaluate the effect of esketamine combined with distal limb ischemic preconditioning(LIP)for lung protection in elderly patients undergoing thoracoscopic radical surgery for lung cancer.Methods This randomized trial was conducted in 160 patients undergoing elective thoracoscopic surgery for lung cancer,who were randomized into control group(with saline injection and sham LIP),esketamine group,LIP group,and esketamine+LIP group(n=40).Before anesthesia induction,according to the grouping,the patients received an intravenous injection with 0.5 mg/kg esketamine or 10 ml saline(in control group).LIP was induced by applying a tourniquet 1-2 cm above the popliteal fossa in the left lower limb to block the blood flow for 5 min for 3 times at the interval of 5 min,and sham LIP was performed by applying the tourniquet without pressurization for 30 min.Oxygenation index(OI)and alveolar-arterial PO2 difference(A-aDO2)were calculated before induction(T0),at 30 min(T0.5)and 1 h(T1)of one-lung ventilation(OLV),and at 1 h after two-lung ventilation(T3).Serum levels of SP-D,CC-16 and TNF-α were measured by ELISA at T0,T1,T2(2 h of OLV),T3,and 24 h after the operation(T4).The length of hospital stay and postoperative pulmonary complications of the patients were recorded.Results Compared with those in the control group,the patients in the other 3 groups had significantly lower CC-16,SP-D and TNF-α levels,shorter hospital stay,and lower incidences of lung infection and lung atelectasis(all P<0.05).Serum CC-16,SP-D and TNF-α levels,hospital stay,incidences of complications were significantly lower or shorter in the combined treatment group than in esketamine group and LIP group(all P<0.05).Conclusion In elderly patients undergoing thoracoscopic radical surgery for lung cancer,treatment with esketamine combined with LIP can alleviate acute lung injury by enhancing anti-inflammatory response to shorten postoperative hospital stay,reduce lung complications and promote the patients'recovery.

Objective To evaluate the effect of esketamine combined with distal limb ischemic preconditioning(LIP)for lung protection in elderly patients undergoing thoracoscopic radical surgery for lung cancer.Methods This randomized trial was conducted in 160 patients undergoing elective thoracoscopic surgery for lung cancer,who were randomized into control group(with saline injection and sham LIP),esketamine group,LIP group,and esketamine+LIP group(n=40).Before anesthesia induction,according to the grouping,the patients received an intravenous injection with 0.5 mg/kg esketamine or 10 ml saline(in control group).LIP was induced by applying a tourniquet 1-2 cm above the popliteal fossa in the left lower limb to block the blood flow for 5 min for 3 times at the interval of 5 min,and sham LIP was performed by applying the tourniquet without pressurization for 30 min.Oxygenation index(OI)and alveolar-arterial PO2 difference(A-aDO2)were calculated before induction(T0),at 30 min(T0.5)and 1 h(T1)of one-lung ventilation(OLV),and at 1 h after two-lung ventilation(T3).Serum levels of SP-D,CC-16 and TNF-α were measured by ELISA at T0,T1,T2(2 h of OLV),T3,and 24 h after the operation(T4).The length of hospital stay and postoperative pulmonary complications of the patients were recorded.Results Compared with those in the control group,the patients in the other 3 groups had significantly lower CC-16,SP-D and TNF-α levels,shorter hospital stay,and lower incidences of lung infection and lung atelectasis(all P<0.05).Serum CC-16,SP-D and TNF-α levels,hospital stay,incidences of complications were significantly lower or shorter in the combined treatment group than in esketamine group and LIP group(all P<0.05).Conclusion In elderly patients undergoing thoracoscopic radical surgery for lung cancer,treatment with esketamine combined with LIP can alleviate acute lung injury by enhancing anti-inflammatory response to shorten postoperative hospital stay,reduce lung complications and promote the patients'recovery.

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.

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.