ABSTRACT
In acupuncture diagnosis and treatment, non-quantitative clinical descriptions have limited the development of standardized treatment methods. This study explores the effectiveness and the reasons for discrepancies in the entity recognition and classification of meridians in acupuncture indication using the Acupuncture Bidirectional Encoder Representations from Transformers (ACUBERT) model. During the research process, we selected 54 593 different entities from 82 acupuncture medical books as the pretraining corpus for medical literature, conducting classification research on Chinese medical literature using the BERT model. Additionally, we employed the support vector machine and Random Forest models as comparative benchmarks and optimized them through parameter tuning, ultimately leading to the development of the ACUBERT model. The results show that the ACUBERT model outperforms other baseline models in classification effectiveness, achieving the best performance at Epoch = 5. The model's "precision," "recall," and F1 scores reached above 0.8. Moreover, our study has a unique feature: it trains the meridian differentiation model based on the eight principles of differentiation and zang-fu differentiation as foundational labels. It establishes an acupuncture-indication knowledge base (ACU-IKD) and ACUBERT model with traditional Chinese medicine characteristics. In summary, the ACUBERT model significantly enhances the classification effectiveness of meridian attribution in the acupuncture indication database and also demonstrates the classification advantages of deep learning methods based on BERT in multi-category, large-scale training sets. Database URL: http://acuai.njucm.edu.cn:8081/#/user/login?tenantUrl=default.
Subject(s)
Acupuncture Therapy , Meridians , Humans , Knowledge Bases , Acupuncture , Support Vector MachineABSTRACT
OBJECTIVES: To observe the effect of electroacupuncture (EA) pre-conditioning on the expression rhythm of clock gene Bmal1 in the uterine tissue of rats with controlled ovarian hyperstimulation(COH), so as to explore its mechanisms underlying improvement of the endometrial receptivity of ovarian superovulation during implantation. METHODS: Seventy-two female SD rats with typical estrous cycles were randomly divided into normal control, model and EA pre-conditioning (pre-EA) groups, with 24 rats in each group. The COH model was established by giving the rats with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) by intraperitoneal injection. The rats of the pre-EA group received EA stimulation (1 Hz/5 Hz, a tolerable strength) of "Guanyuan"(CV4) and "Sanyinjiao"(SP6) for 15 min each time, once daily (at 21ï¼00 every day). After successive EA intervention during the first two estrous cycles, the modeling began in the third estrus cycle and the EA intervention was continued till the end of modeling, followed by raising the rats with superovulation induction and male rats undergoing vasoligation in one cage (1â¶1). The rats during the estrum in the normal control group or those of the model group at the end of modeling were raised together with the male rats undergoing vasoligation in one cage. On the 5th day (04ï¼00 AM) after raising in one cage, the rats in the three groups were sacrificed in six batches every 4 hours, with 4 rats in each group in each batch. The H.E. staining was used for revealing alterations of the endometrial thickness, number of glands and blood vessels and tissue histology, and ELISA employed to ascertain the contents of estradiol (E2) and progesterone (Pg) in serum. The expression rhythm of core clock gene Bmal1 ï¼»In the present study, Zeitgeber time (ZT) is an artificially set laboratory time, i.e., ZT7 (07ï¼00) is light on and ZT19 (19ï¼00) is light off.ï¼½ and the expression of endometrial HoxA10 and leukemia inhibitory factor (LIF) mRNAs were detected by quantitative real-time PCR. The Western blot was employed to detect the expression levels of HoxA10 and LIF proteins. RESULTS: Findings of the clock gene Bmal1 level showed that the expression peak was at ZT12 and the valley value at ZT20 in the normal control group, and that of the peak value was at ZT20 and valley value at ZT12 in the model group, while in the pre-EA group, the peak value was at ZT8, and the valley value at ZT4. The difference of Bmal1 levels among the three groups was most significant at ZT12 (12ï¼00), therefore, the tissue samples were taken at ZT12 in this study for comparison of the levels of different indexes among the 3 groups. Compared with the control group, the endometrial thickness, number of glands and blood vessels, HoxA10 and LIF mRNAs and proteins were significantly down-regulated (P<0.01, P<0.05), and contents of serum E2 and Pg were considerably up-regulated in the model group (P<0.01, P<0.05). Relevant to the model group, the pre-EA group had an apparent increase in the endometrial thickness, number of glands and blood vessels, and expression levels of HoxA10 and LIF mRNAs and proteins (P<0.05, P<0.01), and a marked decrease in the serum Pg (P<0.05). At the ZT12 (12ï¼00 noon), compared with the normal control group, the mRNA level of Bmal1 was significantly decreased in the model group (P<0.01)ï¼and compared with the model group, the level of Bmal1 mRNA was significantly increased in the pre-EA group (P<0.05). In addition, at the node of ZT16, the mRNA level of Bmal1 was significantly decreased in the model group in comparison with the normal control group (P<0.01). CONCLUSIONS: EA preconditioning can improve the endometrial receptivity during the implantation window period in rats with COH, which may be related to its functions in regulating the expression of clock gene Bmal1 in the uterine tissue and in correcting the disturbance of clock gene rhythm.
Subject(s)
ARNTL Transcription Factors , Electroacupuncture , Rats, Sprague-Dawley , Uterus , Animals , Female , Rats , ARNTL Transcription Factors/genetics , ARNTL Transcription Factors/metabolism , Uterus/metabolism , Humans , Male , Acupuncture Points , Ovulation InductionABSTRACT
OBJECTIVES: To observe the effect of electroacupuncture (EA) on the Wnt/ß-catenin signaling pathway and epithelial-mesenchymal transition (EMT)-related proteins in rats with intrauterine adhesions (IUA), so as to explore the possible mechanisms of EA in repairing endometrial damage in IUA. METHODS: Female SD rats were randomly divided into blank, model, EA, and ICG-001 groups, with 10 rats in each group. The IUA model was established by using mechanical scraping combined with lipopolysaccharide infection for double injury. In the EA group, "Guanyuan" (CV4) was needled and EA (2 Hz/15 Hz, 1-2 mA) was applied to "Zusanli" (ST36) and "Sanyinjiao"(SP6) on both sides. In the ICG-001 group, ICG-001 (5 mg/kg), the inhibitor of ß-catenin was intraperitoneally injected. After intervention, samples were taken from 5 rats in each group, and uterine endometrium morphology, endometrial thickness, and gland counts were observed using HE staining. Masson staining was used to assess the degree of fibrosis in the endometrial tissue. Immunohistochemistry was used to detect the positive expression of transforming growth factor ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), fibronectin (FN), connective tissue growth factor (CTGF), type I collagen (Col- â ), glycogen synthase kinase-3ß (GSK-3ß), ß-catenin, E-cadherin, N-cadherin, and Vimentin in the endometrial tissue. Western blot was used to detect the relative expression of GSK-3ß, ß-catenin, E-cadherin, N-cadherin, and Vimentin proteins in the endometrial tissue. Another 5 rats from each group were placed in cages with male rats after intervention to record the number of embryo implantations. RESULTS: Necrosis and loss of endometrial tissue in the model group observed after HE staining were alleviated in the EA group, better than those in the ICG-001 group. Compared with the blank group, the numbers of glands and endometrial thickness in the uterine endometrial tissue, relative expression and positive expression of E-cadherin and GSK-3ß proteins in the uterine endometrial tissue, and embryo implantation numbers were reduced(P<0.000 1, P<0.001, P<0.01) in the model group, while fibrosis area ratio in the uterine endometrial tissue, TGF- ß 1, α -SMA, FN, CTGF, Col- â positive expressions, N-cadherin, Vimentin, and ß-catenin proteins expression and positive expression were increased(P<0.000 1, P<0.001, P<0.01). Compared with the model group, the number of glands and endometrial thickness, E-cadherin and GSK-3ß proteins expression and positive expression, and embryo implantation numbers were increased (P<0.001, P<0.05, P<0.01) in the EA and ICG-001 groups, while the fibrosis area ratio in the uterine endometrial tissue, TGF-ß1, α-SMA, FN, CTGF, Col- â positive expression, and N-cadherin, Vimentin, and ß-catenin proteins expression and positive expression were decreased(P<0.001, P<0.01, P<0.05). Compared with the EA group, the differences of the above-mentioned indicators in the ICG-001 group were not statistically significant. CONCLUSIONS: EA may reverse the EMT process and reduce the degree of fibrosis in endometrial tissue by inhibiting the Wnt/ß-catenin signaling pathway, thereby promoting the repair of endometrial damage in IUA.
Subject(s)
Electroacupuncture , Endometrium , Epithelial-Mesenchymal Transition , Fibrosis , Rats, Sprague-Dawley , Wnt Signaling Pathway , beta Catenin , Animals , Female , Rats , Humans , beta Catenin/metabolism , beta Catenin/genetics , Endometrium/metabolism , Fibrosis/therapy , Fibrosis/genetics , Tissue Adhesions/therapy , Tissue Adhesions/metabolism , Tissue Adhesions/genetics , Uterine Diseases/therapy , Uterine Diseases/metabolism , Uterine Diseases/genetics , Cadherins/metabolism , Cadherins/genetics , Acupuncture Points , Uterus/metabolismABSTRACT
Background: Falls pose a serious health risk for the elderly, particular for those who are living alone. The utilization of WiFi-based fall detection, employing Channel State Information (CSI), emerges as a promising solution due to its non-intrusive nature and privacy preservation. Despite these advantages, the challenge lies in optimizing cross-individual performance for CSI-based methods. Objective: This study aimed to develop a resilient real-time fall detection system across individuals utilizing CSI, named TCS-Fall. This method was designed to offer continuous monitoring of activities over an extended timeframe, ensuring accurate and prompt detection of falls. Methods: Extensive CSI data on 1800 falls and 2400 daily activities was collected from 20 volunteers. The grouped coefficient of variation of CSI amplitudes were utilized as input features. These features capture signal fluctuations and are input to a convolutional neural network classifier. Cross-individual performance was extensively evaluated using various train/test participant splits. Additionally, a user-friendly CSI data collection and detection tool was developed using PyQT. To achieve real-time performance, data parsing and pre-processing computations were optimized using Numba's just-in-time compilation. Results: The proposed TCS-Fall method achieved excellent performance in cross-individual fall detection. On the test set, AUC reached 0.999, no error warning ratio score reached 0. 955 and correct warning ratio score reached of 0.975 when trained with data from only two volunteers. Performance can be further improved to 1.00 when 10 volunteers were included in training data. The optimized data parsing/pre-processing achieved over 20× speedup compared to previous method. The PyQT tool parsed and detected the fall within 100 ms. Conclusions: TCS-Fall method enables excellent real-time cross-individual fall detection utilizing WiFi CSI, promising swift alerts and timely assistance to elderly. Additionally, the optimized data processing led to a significant speedup. These results highlight the potential of our approach in enhancing real-time fall detection systems.
ABSTRACT
By extracting the acupoint names and their main indications from cases in Chinese Acupuncture and Moxibustion Therapy and Practical Acupuncture and Moxibustion, the acupoints and their main indications are represented in a reduced dimension, establishing an "acupoint-indication" linkage. Using complex network detection results (node degree values), the specificity of acupoints was assessed. The small-world characteristics of the "acupoint-indication" network are utilized to analyze the consistency of acupoint selection in acupuncture prescriptions and strategies to avoid redundant acupoints. The results show that the "acupoint-indication" network formed by both texts exhibited an approximate "long-tail" distribution, with a large number of node degree values concentrated between 0 and 4 000, while a few nodes have degree values exceeding 10 000. There are significant differences in the number and distribution of nodes with degree values> 10 000 between the two texts. Chinese Acupuncture and Moxibustion Therapy includes 11 acupoints with multiple edges across the body, whereas Practical Acupuncture and Moxibustion contains only 2 such acupoints, located in the lower limbs. Clinically, some acupoints have a broad therapeutic effect and appear in numerous prescriptions. The division of acupoints based on node degree values can coarsely evaluate the body region specificity of acupoints' regulatory effects. The "acupoint-indication" network of Chinese Acupuncture and Moxibustion Therapy has a higher number of edges than that of Practical Acupuncture and Moxibustion, which might be related to the different historical contexts of the two texts. In the future, diagnostic and therapeutic patterns with historical continuity can be utilized to optimize acupuncture prescriptions.
Subject(s)
Acupuncture Points , Acupuncture Therapy , Moxibustion , Humans , China , Moxibustion/methods , Textbooks as TopicABSTRACT
OBJECTIVES: To observe the effect of electroacupuncture(EA) on endometrial fibrosis and M1-type macrophages in rats with intrauterine adhesions(IUA), so as to explore the possible mechanism of EA in the treatment of IUA. METHODS: Fifteen female SD rats were randomly divided into blank group, model group and EA group, with 5 rats in each group. The IUA rat model was established by double damage method using mechanical scraping combined with lipopolysaccharide infection. Rats in the EA group were treated with acupuncture at "Guanyuan"(CV4), and EA at bilateral "Zusanli"(ST36) and "Sanyinjiao"(SP6)for 20 minutes each time, once a day, for 3 consecutive cycles of estrus. Five rats in each group were sampled during the estrous period, and the endometrial morphology, endometrial thickness and the number of blood vessels and glands were observed after HE staining. The fibrotic area of the uterus was observed after Masson staining. The positive expressions of Runt-related transcription factor(RUNX1), transforming growth factor-ß1(TGF-ß1), connective tissue growth factor(CTGF), α-smooth muscle actin(α-SMA), collagen type I(Col-â ), cluster of differentiation 86(CD86), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α) in endometrial tissue were detected by immunohistochemistry. Western blot was used to detect relative protein expressions of RUNX1, TGF-ß1, α-SMA, CD86, and TNF receptor 2 (TNFR2), and real-time fluorescence quantitative PCR was used to detect mRNA expressions of RUNX1, TGF-ß1, α-SMA, CD86, and TNF-α in the endometrium. RESULTS: During the estrous phase, the endometrial layer in the model group was damaged, with reduced folds, disordered arrangement of epithelial cells, loose fibrous connective tissue, significant narrowing and adhesions in the uterine cavity, interstitial congestion, edema, and a significant infiltration of inflammatory cells with sparse glands. While uterine tissue structure of the EA group was basically intact, resembling a normal uterus, with more newly formed glands and a small amount of inflammatory cell infiltration. In comparison with the blank group, the endometrial thickness, the number of blood vessels, and the number of glands were significantly decreased(P<0.001) in the model group, while the ratio of uterine fibrosis area, the positive expressions of RUNX1, TGF-ß1, CTGF, α-SMA, Col-â , CD86, IL-1ß, and TNF-α, the protein relative expressions of RUNX1, TGF-ß1, α-SMA, CD86 and TNFR2, and the mRNA relative expression levels of RUNX1, TGF-ß1, α-SMA, CD86 and TNF-α in the endometrium were significantly increased (P<0.001, P<0.01). Compared to the model group, the endometrial thickness, the number of blood vessels, and the number of glands were significantly increased(P<0.01, P<0.05) in the EA group, while the ratio of uterine fibrosis area, the positive expressions of RUNX1, TGF-ß1, CTGF, α-SMA, Col-â , CD86, IL-1ß and TNF-α in the endometrial tissue, the protein expressions of RUNX1, TGF-ß1, α-SMA, CD86 and TNFR2, and the mRNA relative expressions of RUNX1, TGF-ß1, α-SMA, CD86 and TNF-α in the endometrium were significantly decreased (P<0.001, P<0.01, P<0.05). CONCLUSIONS: EA can improve endometrial fibrosis in IUA rats, which may be related to its function in decreasing the level of endometrial M1-type macrophages and the secretion of related inflammatory factors.
Subject(s)
Electroacupuncture , Endometrium , Macrophages , Rats, Sprague-Dawley , Animals , Female , Rats , Endometrium/metabolism , Tissue Adhesions/therapy , Tissue Adhesions/metabolism , Tissue Adhesions/genetics , Humans , Macrophages/metabolism , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Acupuncture Points , Uterine Diseases/therapy , Uterine Diseases/metabolism , Connective Tissue Growth Factor/metabolism , Connective Tissue Growth Factor/geneticsABSTRACT
AIMS: The aim of the study is to develop a model using a machine learning approach that can effectively identify the quality of home care in communities. DESIGN: A cross-sectional design. METHODS: In this study, we evaluated the quality of home care in 170 community health service centres between October 2022 and February 2023. The Home Care Service Quality Questionnaire was used to collect information on home care structure, process and outcome quality. Then, an intelligent and comprehensive evaluation model was developed using a convolutional neural network, and its performance was compared with random forest and logistic regression models through various performance indicators. RESULTS: The convolutional neural network model was built upon seven variables, which encompassed the qualification of home nursing staff, developing and practicing emergency plan to cope with different emergency rescues in home environment, being equipped with medication and supplies for first aid according to specific situations, assessing nutrition condition of home patients, allocation of the number of home nursing staff, cases of new pressure ulcers and patient satisfaction rate. Remarkably, the convolutional neural network model demonstrated superior performance, outperforming both the random forest and regression models. CONCLUSION: The successful development and application of the convolutional neural network model highlight its ability to leverage data from community health service centres for rapid and accurate grading of home care quality. This research points the way to home care quality improvement. IMPACT: The model proposed in this study, coupled with the aforementioned factors, is expected to enhance the accuracy and efficiency of a comprehensive evaluation of home care quality. It will also help managers to take purposeful measures to improve the quality of home care. REPORTING METHOD: The reporting of this study (Observational, cross-sectional study) conforms to the STROBE statement. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The application of this model has the potential to contribute to the advancement of high-quality home care, particularly in lower-middle-income communities.
ABSTRACT
Transplantation of bone marrow mesenchymal stem cells (BMSCs) has demonstrated promising clinical utility in the treatment of endometrial injury and the restoration of fertility. However, since the efficacy of BMSCs after transplantation is not stable, it is very important to find effective ways to enhance the utilisation of BMSCs. Electroacupuncture (EA) has some positive effects on the chemotaxis of stem cells and diseases related to uterine injury. In this study, we established the intrauterine adhesion (IUA) model of the Sprague-Dawley rat using lipopolysaccharide infection and mechanical scratching. Phosphate-buffered saline, BMSCs alone, and BMSCs combined with EA were randomly administered to the rats. Fluorescent cell labelling showed the migration of transplanted BMSCs. H&E staining, Masson staining, Western blot, immunohistochemistry, ELISA, and qRT-PCR were utilised to detect changes in endometrial morphology and expressions of endometrial receptivity-related factors, endometrial pro-inflammatory factors, and fibrosis factors. Finally, we conducted a fertility test to measure the recovery of uterine function. The results showed that EA promoted transplanted BMSCs to migrate into the injured uterus by activating the SDF-1/CXCR4 axis. Endometrial morphology showed the most significant improvement in the BMSC + EA group. The expressions of endometrial pro-inflammatory factors and fibrosis indexes in the BMSC + EA group were lower than those in the model and BMSC groups. Further studies revealed that the expression of endometrial receptivity-related factors and the number of embryos implanted on day 8 of gestation increased in the BMSC + EA group compared with the model group and the BMSC group.
Subject(s)
Electroacupuncture , Mesenchymal Stem Cell Transplantation , Rats, Sprague-Dawley , Uterine Diseases , Animals , Female , Electroacupuncture/methods , Mesenchymal Stem Cell Transplantation/methods , Tissue Adhesions , Rats , Uterine Diseases/therapy , Uterine Diseases/pathology , Endometrium/metabolism , Combined Modality Therapy , Recovery of Function , Uterus , Mesenchymal Stem Cells , Receptors, CXCR4/metabolism , Chemokine CXCL12/metabolism , Disease Models, AnimalABSTRACT
Pancreatic adipose tissue serves as a crucial structural basis for the development of glycolipid metabolic disorders. Understanding the mechanisms underlying pancreatic adipose tissue infiltration and regulatory strategies is essential for early intervention in glycolipid metabolic disorders. Pancreatic adipose tissue functions as a significant medium linking systemic immune metabolism, while the pancreatic vascular system emerges as a novel target for sensing pancreatic immune responses and maintaining the body's energy homeostasis, collectively participating in the development of glycolipid metabolic disorders. Acupuncture possesses potential effects in modulating the interaction between resident macrophages and adipocytes in the pancreas, leading to the reversible reduction of excessive pancreatic adipose accumulation, with its action being vascular-dependent.
Subject(s)
Acupuncture Therapy , Metabolic Diseases , Humans , Adipose Tissue/metabolism , Adipocytes/metabolism , Pancreas , Metabolic Diseases/therapy , Metabolic Diseases/metabolismABSTRACT
In the biomedical literature, entities are often distributed within multiple sentences and exhibit complex interactions. As the volume of literature has increased dramatically, it has become impractical to manually extract and maintain biomedical knowledge, which would entail enormous costs. Fortunately, document-level relation extraction can capture associations between entities from complex text, helping researchers efficiently mine structured knowledge from the vast medical literature. However, how to effectively synthesize rich global information from context and accurately capture local dependencies between entities is still a great challenge. In this paper, we propose a Local to Global Graphical Reasoning framework (LoGo-GR) based on a novel Biased Graph Attention mechanism (B-GAT). It learns global context feature and information of local relation path dependencies from mention-level interaction graph and entity-level path graph respectively, and collaborates with global and local reasoning to capture complex interactions between entities from document-level text. In particular, B-GAT integrates structural dependencies into the standard graph attention mechanism (GAT) as attention biases to adaptively guide information aggregation in graphical reasoning. We evaluate our method on three publicly biomedical document-level datasets: Drug-Mutation Interaction (DV), Chemical-induced Disease (CDR), and Gene-Disease Association (GDA). LoGo-GR has advanced and stable performance compared to other state-of-the-art methods (it achieves state-of-the-art performance with 96.14%-97.39% F1 on DV dataset, advanced performance with 68.89% F1 and 84.22% F1 on CDR and GDA datasets, respectively). In addition, LoGo-GR also shows advanced performance on general-domain document-level relation extraction dataset, DocRED, which proves that it is an effective and robust document-level relation extraction framework.
Subject(s)
Data Mining , Data Mining/methodsABSTRACT
OBJECTIVES: To investigate the effects of electroacupuncture(EA) combined with bone marrow mesen-chymal stem cells(BMSCs) transplantation on the endometrium of rats with intrauterine adhesions(IUA), so as to explore the possible mechanisms underlying their combined therapeutic effects. METHODS: Forty adult female SD rats were randomly divided into control, model, cell, and combined groups. The IUA rat model was established using a dual injury method of mechanical scratching and lipopolysaccharide infection. After successful modeling, on days 1, 3, and 7, rats in the model group received tail vein injection of phosphate buffered solution, while rats in the cell group received tail vein injection of BMSCs suspension for BMSCs transplantationï¼and rats in the combined group received BMSCs transplantation combined with EA treatment (2 Hz/15 Hz, 1-2 mA), targeting the "Guanyuan"(CV4), bilateral "Zusanli"(ST36) and "Sanyinjiao"(SP6) for 20 min daily for 3 consecutive estrous cycles. After intervention, uterine tissue was collected from 5 rats in each group. Histological analysis was performed using hematoxylin and eosin staining to evaluate endometrial thickness and glandular number. Masson staining was used to assess endometrial fibrosis area. Immunohistochemistry was performed to detect the positive expressions of vascular endothelial growth factor(VEGF), proliferating cell nuclear antigen(PCNA), and estrogen receptor(ER). Western blot analysis was conducted to determine the protein expressions of homeobox A10(HoxA10) and leukemia inhibitory factor(LIF), both key regulators of endometrial receptivity. The remaining 5 rats in each group were co-housed with male rats, and the uterine function recovery was evaluated by assessing the number of embryo implantations. RESULTS: Compared with the control group, the model group showed thinning endometrium(P<0.001), decreased glandular number(P<0.001), increased endometrial fibrosis area(P<0.001), reduced positive expressions of VEGF, PCNA, ER, expressions of HoxA10 and LIF, and decreased embryo implantation number (P<0.001) on the injured side of the uterus. Compared with the model group, the combined group showed a reversal of the aforementioned indicators(P<0.001, P<0.01)ï¼the cell group exhibited thicker endometrium(P<0.001) and reduced endometrial fibrosis area(P<0.001). Compared with the cell group, the combined group showed increased endometrial thickness(P<0.01), elevated glandular number(P<0.05), significantly decreased endometrial fibrosis area(P<0.05), enhanced positive expressions of VEGF, PCNA and ER, expressions of HoxA10 and LIF in the endometrium, and a significant increase in embryo implantation number (P<0.001, P<0.05, P<0.01) on the injured side of the uterus, indicating better results than the cell group. CONCLUSIONS: The combination of EA and BMSCs synergistically promotes the repair of damaged endometrium, improves endometrial morphology, reduces fibrosis levels, enhances vascular regeneration and matrix cell proliferation, improves endometrial receptivity, which ultimately facilitates embryo implantation.
Subject(s)
Electroacupuncture , Mesenchymal Stem Cell Transplantation , Uterine Diseases , Humans , Rats , Male , Female , Animals , Vascular Endothelial Growth Factor A/genetics , Proliferating Cell Nuclear Antigen/metabolism , Proliferating Cell Nuclear Antigen/pharmacology , Rats, Sprague-Dawley , Mesenchymal Stem Cell Transplantation/methods , Bone Marrow/pathology , Uterine Diseases/genetics , Uterine Diseases/therapy , Uterine Diseases/metabolism , Endometrium/metabolism , FibrosisABSTRACT
Autophagy is a well-conserved metabolic system that maintains homeostasis by relying on lysosomal breakdown. The endometrium of patients with intrauterine adhesion (IUA) and an animal model exhibits impaired autophagy. Autophagy is negatively correlated with inflammation. Activation of autophagy can inhibit the inflammatory response, while defects in autophagy will activate the inflammatory response. Here, we studied whether electroacupuncture (EA) inhibits inflammation and promotes endometrial injury repair by activating endometrial autophagy. The IUA animal model was established by mechanical injury plus lipopolysaccharide infection. EA stimulation was applied to the acupoints Guanyuan (CV4), bilateral Sanyinjiao (SP6), and Zusanli (ST36). The results indicated that EA could improve endometrial morphology, attenuate endometrial fibers, and enhance endometrial receptivity in the rat. EA could increase the autophagosomes of endometrial epithelial cells, increase the levels of LC3 and Beclin1, and decrease the level of p62. Additionally, EA may also suppress the nuclear factor kappa-B (NF-κB) signaling pathway and reduce the release of inflammatory factors. Additionally, the effect of EA was comparable to that of the autophagy agonist rapamycin, and the autophagy inhibitor 3-methyladenine reversed the therapeutic effect of EA. Therefore, we assume that EA may facilitate endometrial healing by activating autophagy and reducing NF-κB signal pathway-mediated inflammation.
Subject(s)
Electroacupuncture , Uterine Diseases , Humans , Female , Rats , Animals , NF-kappa B/metabolism , Signal Transduction/physiology , Uterine Diseases/therapy , Inflammation/therapy , AutophagyABSTRACT
OBJECTIVE: It is to explore, based on stromal cell derived factor 1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signal axis, whether the electroacupuncture (EA) combined with bone marrow mesenchymal stem cells (BMSCs) transplantation can promote thin endometrium regeneration and improve endometrial receptivity, so as to further study its mechanisms underlying improvement of promoting BMSCs homing to repair thin endometrium. METHODS: Thirty matured female SD rats were randomly divided into normal control , model , BMSCs transplantation (BMSCs), BMSCs+AMD3100 (a specific antagonist of CXCR4, BMSCs+AMD3100), BMSCs+EA, and BMSCs+EA+AMD3100 groups, with 5 rats in each group. The thin endometrial model was established by intrauterine injection of 95% ethanol during the period of estrus. Rats of the model group received intravenous injection of PBS solution (tail vein) on day 1, 3 and 7 of modeling and intraperitoneal injection of normal saline once daily for 3 estrous cycles. Rats of the BMSCs group received intravenous injection of BMSCs suspension on day 1,3 and 7 of modeling, and those of the BMSCs+EA group received BMSCs transplantation and EA stimulation. EA (2 Hz/15 Hz, 1 mA) was applied to "Guanyuan" (CV4) and bilateral "Sanyinjiao"(SP9), "Zigong" (EX-CA1) for 15 min, once daily for 3 estrous cycles. Rats of the BMSCs+AMD3100 group received intravenous injection of BMSCs suspension (1×106/mL) and intraperitoneal injection of AMD3100 (5 mg/kg), and those of the BMSCs+EA+AMD3100 group received administration of BMSCs, AMD3100 and EA, with both groups being once daily for 3 estrous cycles. H.E. staining was used to observe histopathological changes of endometrium tissues, and immunohistochemistry was used to detect the expressions of cytokeratin (CK19) and vimentin in endometrium (for evaluating the damage and repair of endometrium). The expression levels of homeobox A10 (HOXA10), leukemia inhibitory factor (LIF), SDF-1 and CXCR4 proteins were detected by Western blot, and those of SDF-1 and CXCR4 mRNAs in the endometrium detected by real-time PCR. RESULTS: In comparison with the normal control group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression leve-ls of HOXA10, LIF and CXCR4 proteins and CXCR4 mRNA were significantly down-regulated (P<0.01), and the expression levels of SDF-1 protein and mRNA significantly up-regulated (P<0.05) in the model group. Compared with the model group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, and the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs group, and the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA, and SDF-1 protein and mRNA in the BMSCs+EA group were significantly up-regulated (P<0.05, P<0.01). Compared to the BMSCs group, the number of endometrial glands, and the expression levels of LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+EA group were up-regulated (P<0.01, P<0.05)ï¼ the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+AMD3100 group were down-regulated (P<0.01). Compared to the BMSCs+EA group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+EA+AMD3100 group were down-regulated (P<0.01). Results of H.E. staining showed thin endometrium with absence of epithelial cells, and sparse glands and blood vessels, with smaller glandular cavity in the model group, which was relative milder in BMSCs and BMSCs+EA groups. CONCLUSION: EA can promote the transfer of transplanted BMSCs to the damaged site through SDF-1/CXCR4 signaling related stem cell homing, thereby promoting thin endometrial regeneration, repairing endometrial injury, and improving endometrial tolerance in rats with thin endometrium.
Subject(s)
Electroacupuncture , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Female , Animals , Rats , Rats, Sprague-Dawley , Vimentin , Receptors, CXCR4/genetics , Chemokine CXCL12/genetics , Bone Marrow , EndometriumABSTRACT
OBJECTIVE: To observe the effect of electroacupuncture (EA) on the degree of endometrial fibrosis and inflammatory response in the rat model of intrauterine adhesion (IUA), so as to explore the possible mechanism of EA underlying improving IUA and promoting endometrium regeneration. METHODS: Forty-five female SD rats were randomly divided into blank, model and EA groups, with 15 rats in each group. The IUA model was established by mechanical scratching combined with lipopolysaccharide infection. EA was applied to bilateral "Zigong" (EX-CA1) and "Sanyinjiao" (SP6), with acupuncture applied to "Guanyuan" (CV4) for rats in the EA group, started from the 2nd day after modeling, 15 minutes every time, once a day for 2 consecutive estrous cycles. Samples from 5 rats in each group were collected during estrus period. Changes of endometrial histopathology and number of glands were observed after HE staining. The area of endometrial fibrosis was observed and calculated after Masson staining. The positive expressions of collagen type I (Col-I) and transforming growth factor ß1 (TGF-ß1) proteins in endometrial tissue were detected by immunohistochemistry method. The protein expression of integrin αγß3 in uterine tissue was detected by Western blot. The contents of interleukin (IL)-1ß and tumor necrosis factor α (TNF-α) in uterine tissue were detected by ELISA. Samples from remaining 10 rats in each group were collected on the 8th day of gestation for calculation of the embryo implantation numbers of the rats. RESULTS: HE staining showed complete uterine tissue structure of the rats in the blank group during estrus period, with clear endometrial layer, unobstructed and regular uterine cavity, and dense glands. Destroyed endometrial layer, narrowed and adhered uterine cavity, and sparse glands of the rats were seen in the model group, which was relatively milder in the EA group. Following modeling, the number of endometrial glands, the protein expression of Integrin αγß3, the number of implanted uterine embryos on the injured side of the model group were significantly decreased (P<0.01), while the area of endometrial fibrosis, the positive expressions of Col-I and TGF-ß1 proteins, and the contents of IL-1ß and TNF-α in the uterine tissue were significantly increased (P<0.01) in comparison with those in the blank group. After intervention, the number of endometrial glands, the protein expression of Integrin αγß3, the number of implanted uterine embryos on the injured side of the EA group were significantly increased (P<0.01ï¼P<0.05), while the area of endometrial fibrosis, the positive expressions of Col-I and TGF-ß1 proteins, and the contents of IL-1ß and TNF-α in the uterine tissue were significantly decreased (P<0.01,P<0.05) compared with the model group. CONCLUSION: EA can enhance endometrial receptivity, and promote endometrial regeneration, be conducive to embryo implantation in IUA model rats, which may be related to its effect in alleviating endometrial fibrosis and reducing inflammatory response.
Subject(s)
Electroacupuncture , Transforming Growth Factor beta1 , Female , Animals , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta1/genetics , Tumor Necrosis Factor-alpha/genetics , Endometrium , Integrins , Regeneration , FibrosisABSTRACT
OBJECTIVE: To observe the effects of moxibustion preconditioning on ovarian function, fertility and ovarian granulosa cell apoptosis in rats with premature ovarian insufficiency (POI), so as to investigate its underlying mechanism in improving POI. METHODS: Forty-two female SD rats with two complete estrous cycles were randomly divided into control group, model group and pre-moxibustion group, with 14 rats in each group. The pre-moxibustion group was pretreated with mild moxibustion for 14 days before POI model establishment at 1) "Guanyuan" (CV4) and "Zhongwan" (CV12) and 2) bilateral "Shenshu" (BL23) as two sets of acupoints on alternate days, once each day, for 10 min each acupoint. After 14-day mild moxibustion intervention, 75 mg·kg-1·d-1 tripterygium glycoside tablet suspension was administered to rats in the pre-moxibustion group and the model group by gavage, for 14 consecutive days, while equivalent saline was given to rats in the control group in the same way. After modeling, the effect of moxibustion preconditioning on ovarian reserve function was evaluated by the estrous cycles, pregnancy rate and embryo number, morphological changes of ovaries, and serum sex hormone levels. TUNEL staining was used to detect the rate of granulosa cell apoptosis in ovaries. Immunohistochemistry and real time quantitative PCR were used to detect the relative expression of Caspase-3 and Caspase-9 proteins and mRNA levels in ovaries. RESULTS: Compared with the control group, the estrous cycles were disturbed; the pregnancy rate and number of embryos, the wet weight of ovary and ovarian index, the number of total follicles and different level of follicles, serum Estradiol (E2) and anti-mullerian hormone (AMH) levels were all significantly decreased (P<0.01,P<0.05), while the number of atretic follicles, serum follicule-stimulating hormone (FSH) and luteinizing hormone (LH) levels, the number of TUNEL-positive granulosa cells, the expression of ovarian Caspase-3 and Caspase-9 proteins and mRNAs were significantly increased (P<0.01) in the model group. Compared with the model group, the disordered estrous cycles were improved; the pregnancy rate, the embryo numbers, the wet weight of ovary, and the total follicle number and primary follicle number, serum AMH level were significantly increased (P<0.01ï¼P<0.05), while the number of atretic follicles, serum FSH level, the number of TUNEL-positive granulosa cells, expression of ovarian Caspase-3 and Caspase-9 proteins and mRNAs were all significantly decreased (P<0.01,P<0.05) in the moxibustion group. CONCLUSION: Moxibustion preconditioning could improve ovarian function and improve fertility of POI rats, which may be associated with reducing the apoptosis of ovarian granulosa cells.
Subject(s)
Moxibustion , Primary Ovarian Insufficiency , Pregnancy , Humans , Rats , Female , Animals , Caspase 3/genetics , Caspase 9 , Rats, Sprague-Dawley , Primary Ovarian Insufficiency/genetics , Primary Ovarian Insufficiency/therapy , Follicle Stimulating HormoneABSTRACT
Identifying high-order Single Nucleotide Polymorphism (SNP) interactions of additive genetic model is crucial for detecting complex disease gene-type and predicting pathogenic genes of various disorders. We present a novel framework for high-order gene interactions detection, not directly identifying individual site, but based on Deep Learning (DL) method with Differential Privacy (DP), termed as Deep-DPGI. Firstly, integrate loss functions including cross-entropy and focal loss function to train the model parameters that minimize the value of loss. Secondly, use the layer-wise relevance analysis method to measure relevance difference between neurons weight and outputting results. Deep-DPGI disturbs neuron weight by adaptive noising mechanism, protecting the safety of high-order gene interactions and balancing the privacy and utility. Specifically, more noise is added to gradients of neurons that is less relevance with the outputs, less noise to gradients that more relevance. Finally, Experiments on simulated and real datasets demonstrate that Deep-DPGI not only improve the power of high-order gene interactions detection in with marginal and without marginal effect of complex disease models, but also prevent the disclosure of sensitive information effectively.
ABSTRACT
OBJECTIVE: To explore the effect of electroacupuncture on endometrial receptivity and the pregnancy outcomes of in vitro fertilization and embryo transfer (IVF-ET) in the patients with diminished ovarian reserve (DOR). METHODS: Sixty-eight patients of DOR undertaken IVF-ET were randomized into an observation group (34 cases, 2 cases dropped off) and a control group (34 cases, 1 case dropped off). In the control group, endometrial preparation was performed according to the routine protocol. In the observation group, on the base of the treatment as the control group, acupuncture was applied to Geshu (BL 17), Shenshu (BL 23), Mingmen (GV 4), Shiqizhui (EX-B 8), Ciliao (BL 32), Zhongliao (BL 33), Tianshu (ST 25), Qihai (CV 6) and Guanyuan (CV 4), etc. Electric stimulation was given at Ciliao (BL 32)-Zhongliao(BL 33), Tianshu (ST 25)-Zigong (EX-CA 1), with disperse-dense wave, 2 Hz/15 Hz in frequency and tolerable current in intensity. Electroacupuncture was given once every two days, 3 times weekly, lasing 3 menstrual cycles till 1 day before embryo transfer. The endometrial thickness and morphology were observed on the day of human chorionic gonadotropin (HCG) of egg retrieval cycle, the day of endometrial transformation in frozen-thawed embryo transfer (FET) cycle and the day of embryo transfer in both groups successively; as well as HCG positive rate, clinical pregnancy rate, embryo implantation rate and live birth rate. RESULTS: In the observation group, the proportion of type A endometrium on the embryo transfer day was higher than those on HCG day of the egg retrieval cycle and the endometrial transformation day of FET cycle (P<0.05), and also higher than that of the control group (P<0.01). In the observation group, HCG positive rate, clinical pregnancy rate, embryo implantation rate and live birth rate were 75.0% (24/32), 71.9% (23/32), 47.4% (27/57) and 56.3% (18/32) respectively, and all higher than 36.4% (12/33), 30.3% (10/33), 18.0% (11/61) and 15.2% (5/33) in the control group separately (P<0.01). CONCLUSION: Electroacupuncture improves the endometrial receptivity and IVF-ET pregnancy outcomes in the patients of diminished ovarian reserve.
Subject(s)
Electroacupuncture , Ovarian Diseases , Ovarian Reserve , Chorionic Gonadotropin , Endometrium , Female , Fertilization in Vitro , Humans , Pregnancy , Pregnancy Outcome , Pregnancy RateABSTRACT
Rationale: Aberrant activation of macrophages with mitochondria dismiss was proved to be associated with pathogenesis of ALI (acute lung injury). Exosomes from adipose-derived mesenchymal stem cells (AdMSC-Exos) have been distinguished by their low immunogenicity, lack of tumorigenicity, and high clinical safety, but their role in treating ALI and the mechanism involved need to be defined. In this study, we sought to investigate whether the mitochondrial donation from AdMSC-Exos provides profound protection against LPS-induced ALI in mice, accompanied by improvement of macrophage mitochondrial function. Methods: C57BL/6 mice were orotracheally instilled with LPS (1 mg/kg). AdMSC-Exos were administered via the tail vein 4 h after LPS inhalation. Flow cytometry, H&E, Quantitative Real-Time PCR, immunofluorescence (IF), confocal microscopy imaging was conducted to investigate lung tissue inflammation and macrophage mitochondrial function. And further observe the transfer of exosomes and the effect on mitochondrial function of MH-S cells through in vitro experiments. Results: AdMSC-Exos can transfer the stem cell-derived mitochondria components to alveolar macrophages in a dose-dependent manner. Likely through complementing the damaged mitochondria, AdMSC-Exos exhibited the ability to elevate the level of mtDNA, mitochondrial membrane potential (MMP), OXPHOS activity and ATP generation, while reliving mROS stress in LPS-challenged macrophages. Restoring mitochondrial integrity via AdMSC-Exos treatment enabled macrophages shifting to anti-inflammatory phenotype, as featured with the down-regulation of IL-1ß, TNF-α and iNOS secretion and increase in production of anti-inflammatory cytokines IL-10 and Arg-1. As we depleted alveolar macrophages using clodronate liposomes, the protective role for AdMSC-Exos was largely abrogated. Conclusions: AdMSC-Exos can effectively donate mitochondria component improved macrophages mitochondrial integrity and oxidative phosphorylation level, leading to the resumption of metabolic and immune homeostasis of airway macrophages and mitigating lung inflammatory pathology.
Subject(s)
Acute Lung Injury , Exosomes , Acute Lung Injury/chemically induced , Acute Lung Injury/metabolism , Acute Lung Injury/therapy , Animals , Exosomes/metabolism , Homeostasis , Lipopolysaccharides/metabolism , Macrophages, Alveolar , Mice , Mice, Inbred C57BLABSTRACT
[This corrects the article DOI: 10.3892/etm.2021.10664.].