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.

BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

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*

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

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

Objective:To investigate the spatial distribution patterns of local tumor progression（LTP）after microwave ablation（MWA）for colorectal liver metastases（CRLMs）and identify high-risk progression zones.Methods:A total of 471 CRLM lesions from 246 patients treated with MWA at the Chinese PLA General Hospital between September 2009 and March 2022 were retrospectively analyzed. Three-dimensional visualized MRI image fusion technology was employed to evaluate the spatial relationship between ablation margins（AM）and LTP. The liver was partitioned into nine specific anatomical regions. Machine learning（Boruta algorithm）was used to assess the importance of these regions on LTP risk. Multivariate analysis of LTP was performed at the tumor level and at the patient level using the Cox mixed effects model and the Cox regression model，respectively.Results:LTP occurred in 115 lesions，with an LTP rate of 40.0%（80/200）in ablated lesions which were located in the high-risk progression area，and 12.9%（35/271）in low-risk progression area. Multivariate analysis identified AM < 5 mm，tumor size ≥3 cm and location in high-risk zones as independent risk factors for LTP. Notably，LTP in high-risk zones predominantly clustered around the ablation needle tip.Conclusions:Post-MWA LTP in CRLMs exhibits distinct spatial clustering，particularly at the needle tip within high-risk progression zones. These findings provide critical insights for optimizing ablation strategies and improving clinical outcomes.

Objective:To analyze the liver histological characteristics and clinically related factors in inactive hepatitis B surface antigen (HBsAg) carriers (IHC), and also explore whether antiviral treatment is necessary for IHC, as defined in the 2022 version of the hepatitis B prevention and treatment guidelines.Methods:A multicenter, retrospective cohort study was conducted. Two hundred and thirty-one IHC cases who underwent liver biopsy histopathological examination in nine medical institutions, including Beijing Youan Hospital affiliated with Capital Medical University, from January 2018 to December 2023 were included. General informative data, clinical serological markers, and transient elastography (TE) examination results were collected. Patients were divided into a positive (148 cases) and a negative group (83 cases) according to the results of hepatitis B virus (HBV) DNA detection. The differences in liver pathological inflammatory activity (G) and liver fibrosis stage (S) were analyzed between the two groups to explore the correlation between liver tissue conditions and clinically related factors. Comparsions of normally distributed continwous data, skeukd continuous data, and categorical data between groups are performed using t tests, Mann-Whitney U tests and χ2 tests, respectively. Results:The age of 231 IHC cases was 43 (38, 51) years old, with 95.2% (220/231) aged ≥30 years, and males accounted for 64.9% (150/231). HBsAg and HBV DNA levels were 131.9 (20.8, 400.9) IU/mL and 94.0 (0, 448.5) IU/mL, respectively, of which 35.9% (83/231) were HBV DNA negative (<20 IU/mL). The remarkable proportions of G≥2, S≥2, and liver injury (G≥2 and/or S≥2) in liver tissue were 16.5% (38/231), 29% (67/231), and 35.9% (83/231), respectively. The S≥2 proportion was significantly higher in the HBV DNA-negative group than the positive group (42.2% vs. 21.6%, P<0.001), and it mainly occurred in the population cohort over 30 years old (44.9% vs. 31.0%, P=0.04). The liver stiffness measurement (LSM), aspartate transaminase to platelet ratio index (APRI), and platelet (PLT) were significantly higher in the S≥2 group than the S<2 group ( P<0.05). Conclusion:Clinicians can comprehensively evaluate the degree of liver fibrosis in IHC based on clinical factors such as age, PLT, APRI, and LSM, even if the liver histological results are lacking. The China 2022 version guidelines define that nearly half of IHC has histological indications for antiviral therapy, and liver biopsy and prompt treatment can be recommended.