Objective: To explore the feasibility of remotely obtaining complex information on traditional Chinese medicine (TCM) pulse conditions through voice signals. Methods: We used multi-label pulse conditions as the entry point and modeled and analyzed TCM pulse diagnosis by combining voice analysis and machine learning. Audio features were extracted from voice recordings in the TCM pulse condition dataset. The obtained features were combined with information from tongue and facial diagnoses. A multi-label pulse condition voice classification DNN model was built using 10-fold cross-validation, and the modeling methods were validated using publicly available datasets. Results: The analysis showed that the proposed method achieved an accuracy of 92.59% on the public dataset. The accuracies of the three single-label pulse manifestation models in the test set were 94.27%, 96.35%, and 95.39%. The absolute accuracy of the multi-label model was 92.74%. Conclusion Voice data analysis may serve as a remote adjunct to the TCM diagnostic method for pulse condition assessment.

Objective:To characterize the biomechanics of distal dynamic locking and distal static locking of proximal femur bionic nails (PFBN) in fixation of intertrochanteric fractures by a finite element analysis.Methods:The CT image data from the hip to the upper tibia from an adult male volunteer were used to establish a three-dimensional model of the femur by Mimics 20.0 and Geomagic 2013 which was processed further into a model of Evans type I intertrochanteric fracture by software NX 12.0. With reference to the internal fixation parameters commonly used, 4 models of PFBN fixation were established: distal single transverse nail dynamic locking (model A), single oblique nail dynamic locking (model B), single nail static locking (model C) and double nail dynamic locking (model D). Abaqus 6.14 software was used to load and analyze the internal fixation stresses and displacements of fracture ends.Results:Under a 2100N loading, the peak stress was located upon the main nail in the 4 models. The smallest peak stress upon the main nail was in Model D (161.9 MPa), decreased by 15.9% compared with model A (192.5 MPa), by 15.6% compared with model B (191.9 MPa), and by 0.9% compared with model C (163.3 MPa). The peak stress upon the fixation screw was the largest in model A (95.3 MPa), the smallest in model B (91.5 MPa), and 91.5 MPa and 92.2 MPa in models C and D, respectively. The overall displacements of the implants, in a descending order, were 10.14 mm in model A, 10.10 mm in model B, 10.09 mm in model C, and 10.05 mm in model D. Similarly, the displacements of fracture ends were 0.125 mm in model A, 0.121 mm in model B, 0.110 mm in model C, and 0.098 mm in model D.Conclusion:Compared with dynamic locking, distal static locking of PFBN provides a better mechanical stability and reduces stress concentration upon internal fixation.

Objective To discuss the effect of multidisciplinary family empowerment mode in home care for patients after receiving percutaneous endoscopic gastrostomy(PEG).Methods A total of 86 patients,who received initial PEG at the Jilin Provincial Cancer Hospital of China from January 2021 to July 2023,were selected for this study.The patients were randomly divided into observation group.The patients of the control group received routine nursing guidance for gastrostomy,while the patients of the observation group received multidisciplinary family empowerment nursing mode.The self-care ability[using self-care ability scale of the elderly(SASE)score],health behavior ability[using self-rating scale of health behavior ability(SRAHP)score],incidence of complications,and healing time of complications were compared between the two groups.Results In the observation group the SASE[(129.48±5.48)points vs.(73.05±12.04)points]and the SRAHP[(80.14±1.00)points vs.(70.25±7.92)points]were significantly higher than those in the control group(all P＜0.05),the incidence of complications was lower than that in the control group,and the healing time of complications was shorter than that in the control group.Conclusion The implementation of multidisciplinary family empowerment nursing mode can improve the self-care ability and health behavior ability of patients after receiving PEG,reduce postoperative complications,as well as shorten the healing time of complications,therefore,this nursing mode is suitable for home patients after receiving PEG.

Objective:Using bioinformatics methods to study the immune infiltration mechanism of lupus nephritis(LN)and to explore potential target Chinese medicines,which can provide new directions for clinical treatment of LN.Methods:Gene expres-sion profile microarray dataset of LN was downloaded from GEO database,differential expressed genes(DEGs)were screened using R software,and GO and KEGG enrichment analysis were performed on these DEGs.Protein interaction network analysis of DEGs was performed by applying STRING database,key genes were screened by using Cytoscape,core gene expression was validated by Nephro-seq database,and the infiltration and correlation of 22 kinds of immune cells in LN were calculated by CIBERSORT deconvolution algorithm.Finally,herbal prediction of significantly enriched immune-related biological processes and key target genes were performed by Coremine Medical database.Results:A total of 367 LN-related DEGs were obtained,of which 253 were up-regulated and 114 were down-regulated.GO was mainly enriched in response to viruses,defense response to viruses,regulation of viral life cycle,regulation of viral processes,etc;KEGG was mainly enriched in S.aureus infection,COVID-19,influenza A,complement and coagulation cascade,pertussis,etc.Ten key genes were screened:IFIT3,OAS2,MX1,OAS1,RSAD2,XAF1,ISG15,IFIT1,ITGAM and PTPRC.Immune infiltration by CIBERSORT deconvolution algorithm showed that monocytes and initial B cells were highly expressed in LN,while memory B cells,naive CD4+T cells,follicular helper T cells and resting natural killer cells were lowly expressed in LN.Immune cell correlation analysis showed a positive correlation between initial B cells and plasma cells,a positive correlation between resting natural killer cells and resting dendritic cells,a negative correlation between monocytes and regulatory T cells,and a negative correlation between resting CD4+memory T cells and monocytes.Coremine Medical predicted that Salvia miltiorrhiza,Panax notogin-seng,Scutellaria baicalensis,ginseng,honey,monkey mushroom and peony were found to be most closely related to immunity in LN.Conclusion:The development and progression of LN are results of the combined involvement of multiple genes and pathways.Mono-cytes,memory B cells,initial CD4+T cells and initial B cells are most closely associated with LN.The predicted Salvia miltiorrhiza,Panax notoginseng,Scutellaria baicalensis,ginseng,honey,monkey mushroom and peony may be used as target herbs for the poten-tial treatment of LN.

Objective : To investigate the role and mechanism of bone formation caused by the ratio of advanced platelet-rich fibrin (A-PRF) and β-tricalcium phosphate (β-TCP) in rabbit femur defect model, which provides a new idea for clinical treatment of bone defect. Methods : Twenty-four New Zealand white rabbits were divided into model group, 1∶1 complex group (A-PRF∶β-TCP=1∶1), 2∶1 complex group (A-PRF∶β- TCP=2∶1) and 4∶1 complex group (A-PRF∶β- TCP=4∶1）, with 6 rabbits in each group. Femoral defect models were constructed in each group. In the composite group, the bone defect was filled with composite material, while in the model group, no material was filled. After 8 weeks, the animals were euthanized and specimens were collected. Bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.SP) and trabecular number (Tb.N) in femoral defect tissue were measured by micro-CT and photographed. Hematoxylin - eosin staining was used to detect the pathological changes of new bone tissue. The morphological changes of the new bone tissue were observed by scanning electron microscopy. Determination of phospho-mitogen activated protein kinase p38 (p-p38MAPK), CCAAT/enhancer binding protein homologous protein (CHOP) and phospho-cysteine aspartic protease-3 (p-Caspase3) in newborn femur by ELISA. The mRNA expressions of osteoprotegerin (OPG), bone morphogenetic protein-2 (BMP-2), receptor activator of nuclear factor kappa-B ligand (RANKL) and p38MAPK were detected by real-time quantitative PCR. The expression of OPG, BMP-2, RANKL, p-p38MAPK and p-Caspase3 protein in the new bone tissue was observed by immunohistochemistry. Results : In the model group, bone formation in the femoral defect area was slow and osteogenic quality was poor. Compared with the model group, the bone formation and neocapillaries of femoral defect area in the complex group was good, BMD, BV.TV, Tb.Th, Tb.N were increased, and Tb.Sp were decreased, the expressions of p-p38MAPK, CHOP and p-Caspase3 were decreased, and the mRNA and protein expressions of OPG and BMP-2 were increased. The mRNA expression of RANKL and p38MAPK was decreased. Apoptosis in new bone tissue of each group showed the lowest apoptosis rate in samples of the 2∶1 complex group (P<0.05); A-PRF: β-TCP=2∶1 ratio has the best osteogenic effect. Conclusion The complex composed of A-PRF and β-TCP can promote the expression of OPG, inhibit the expression of RANKL and phosphorylation of p38MAPK, reduce the apoptosis of new bone tissue cells, and promote osteogenic differentiation.

Objective:To study the effects of Zuogui Pills on the expressions of miR-133b-3p and RhoA in osteoclasts of postmenopausal osteoporosis rats; To discuss its potential mechanism.Methods:SD female rats were randomly divided into normal group, model group, sham-operation group, and Zuogui Pills group using a random number table method, with 6 rats in each group. The model group and Zuogui Pills group were treated with oophorectomy to construct a rat model of osteoporosis. Zuogui Pills group was orally administered with Zuogui Pills decoction at a concentration of 10 g/kg for 12 consecutive weeks. Colorimetric method was used to measure the serum calcium and phosphorus levels of rats, and ELISA method was used to detect ALP levels. Bone density meter was used to measure the bone density of the femurs of rats in each group. The osteoclast of each group were cultured, and the expressions of RANKL and RUNX2 protein were detected by Western blot. MiRNA sequencing and differential expression analysis were performed on bone tissues of rats. Osteoclasts were treated with miR-133b-3p mimic and its negative control. The cell proliferation activity of osteoclasts was detected by cell counting kit-8 (CCK-8). The osteoclast differentiation activity was detected by the tartrate-resistant acid phosphatase staining. The dual-luciferase reporter assay was used to detect the relationship between miR-133b-3p and RhoA. The "rescue" experiment of miR-133b-3p mimic and RhoA co-expression were used to study the molecular regulatory mechanism of Zuogui Pills on osteoclast activity.Results:Compared with the model group, the bone mineral density of Zuogui Pills group significantly increased ( P<0.05, P<0.01), the levels of calcium and phosphorus in serum increased, the level of alkaline phosphatase ALP decreased ( P<0.05), the expression of RANKL protein decreased, and the expression of RUNX2 protein increased. Sequencing results showed that rno-miR-133b-3p was down-regulated in osteoclasts of postmenopausa osteoporosis rats treated with Zuogui Pills with the maximum difference ( P<0.01). Q-PCR results showed that the expression of miR-133b-3p in osteoclasts of Zuogui Pills group was significantly lower than that of the model group. The upregulation of miR-133b-3p could significantly promote the cell proliferation and differentiation of osteoclasts. RhoA overexpression could reverse the excessive proliferation and differentiation of osteoclasts caused by miR-133b-3p overexpression. Conclusions:RhoA is the target gene regulated by miR-133b-3p. Zuogui Pills can inhibit the activity of osteoclasts by regulating miR-133b-3p/RhoA axis, relieving the symptoms of osteoporosis.

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate C_pk integrated Bootstrap-t. The C_pk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.

Objective Using bioinformatics methods to study the immune infiltration mechanism of Primary Sj?gren's syndrome(pSS)and to explore potential target Chinese medicines,which can provide new directions for the clinical treatment of pSS.Methods Gene expression profile microarray dataset of pSS was downloaded from the GEO database,differential genes were screened using R software,and gene ontology(GO)and gene pathway enrichment(KEGG)enrichment analysis was performed on these differential genes.Protein interaction network analysis of differential genes was performed by applying the STRING database,key genes were screened by using Cytoscape,and ELISA for the verification of key genes expression.Immune infiltration and correlation of immune cells in pSS were calculated by CIBERSORT inverse convolution method in 22.Finally,the herbal prediction of key target genes was performed by using the Coremine Medical database.Results A total of 232 differential genes were obtained,of which 207 were up-regulated and 25 were down-regulated.GO was mainly enriched in:leukocyte mediated immunity,lymphocyte mediated immunity,leukocyte cell-cell adhesion,etc;KEGG was mainly enriched in Hematopoietic cell lineage,Primary immunodeficiency,Intestinal immune network for IgA production,Phagosome,Leishmaniasis.Ten key genes were screened:PTPRC,CD19,LCP2,CCR5 and CD69 etc.The hub genes expression in the pSS is the same as that of GSE40611.Immune infiltration showed that memory B cells,T cells CD4 memory activated,and T cells CD4 na?ve were highly expressed in the pSS.Immune cell correlation analysis showed a positive correlation between initial Monocytes and T cells regulatory(Tregs),a positive correlation between Macrophages M1 and B cell na?ve,and a negative correlation between Plasma cells and T cells CD4 memory activated.COREMINE Medical predicted that Ginseng,Panax notoginseng,Tripterygium wilfordii,Burnet,Magnolia,and Strychni may treat pSS.Conclusion The development and progression of pSS are the results of the combined involvement of multiple genes and pathways.Memory B cells,T cells CD4 memory activated,and T cells CD4 na?ve may promote the development of pSS.The predicted Ginseng,Panax notoginseng,Tripterygium wilfordii,Burnet,Magnolia,Strychni may be used as target herbs for the potential treatment of pSS.

As the most common neurodegenerative disease, Alzheimer's disease (AD) is characterized by progressive cognitive decline and is a major threat to the health of elderly worldwide. Aside from its pathogenesis, delineation of the protective mechanism of AD is also critical for the etiological treatment. AD resilience refers to a protective mechanism which can maintain the cognitive intactness of patients despite of genetic risk factors and/or related pathology. Studies on the genetic mechanism of AD resilience are of great importance for revealing novel mechanisms and therapeutic targets, as well as optimizing polygenic risk score which can facilitate early identification and intervention for individuals at risk.
Aged ; Humans ; Alzheimer Disease/genetics* ; Neurodegenerative Diseases ; Cognitive Dysfunction

BACKGROUND: Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans. METHODS: We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient. RESULTS: The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion. CONCLUSION Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.
Aged ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Arteries ; Atrophy ; Brain/metabolism* ; Cerebral Cortex/metabolism* ; Cerebrovascular Circulation ; Constriction, Pathologic/pathology* ; Female ; Humans ; Magnetic Resonance Imaging/methods* ; Male ; Middle Aged ; Positron-Emission Tomography/methods*