Multiple system atrophy (MSA) is a rare neurodegenerative disease with complex clinical manifestations, presenting substantial challenges in clinical diagnosis and treatment. Its symptoms and the eight extraordinary meridians are potentially correlated; therefore, this article explores the association between MSA symptom clusters and the eight extraordinary meridians based on their circulation and physiological functions, as well as their treatment strategies. The progression from deficiency to damage in the eight extraordinary meridians aligns with the core pathogenesis of MSA, which is characterized by "the continuous accumulation of impacts from the vital qi deficiency leading to eventual damage". Liver and kidney deficiency and the emptiness of the eight extraordinary meridians are required for the onset of MSA; the stagnation of qi deficiency and the gradual damage to the eight extraordinary meridians are the key stages in the prolonged progression of MSA. The disease often begins with the involvement of the yin and yang qiao mai, governor vessel, thoroughfare vessel, and conception vessel before progressing to multiple meridian involvements, ultimately affecting all eight extraordinary meridians simultaneously. The treatment approach emphasizes that "the direct method may be used for joining battle, but indirect method will be needed in order to secure victory" and focuses on "eliminate pathogenic factors and reinforce healthy qi". Distinguishing the extraordinary meridians and focusing on the primary symptoms are pivotal to improving efficacy. Clinical treatment is aimed at the target, and tailored treatment based on careful clinical observation ensures precision in targeting the disease using the eight extraordinary meridians as the framework and core symptoms as the specific focus. Additionally, combining acupuncture, daoyin therapy, and other method may help prolong survival. This article classifies clinical manifestations based on the theory of the eight extraordinary meridians and explores treatment.

Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.

Objective:To investigate the expressions of cystathionine-β-synthase(CBS)and cystathionine-γ-lyase(CSE)and their effects on the malignant biological behaviours of breast cancer cells,and to elucidate their mechanisms.Methods:The breast cancer tissue and paracancerous normal tissue from 15 cases of patients were selected,and RT-qPCR and Western blotting methods were used to detect the mRNA and protein expression levels of CBS and CSE in breast cancer tissue,paracancerous normal tissue,MCF-7 cells,and MDA-MB-231 cells.The MCF-7 cells were divided into siNC group(transfected with siNC)and siCBS group(transfected with siCBS),and the MDA-MB-231 cells were divided into ovNC group(transfected with CSE over-expression empty plasmid)and ovCSE group(transfected with CSE over-expression plasmid).CCK8 assay was used to detect the proliferation activities of breast cancer cells in various groups,Transwell assay was used to detect the numbers of migration and invasion cells in various groups,and Western blotting method was used to detect the protein expression levels of E-cadherin,N-cadherin and Vimentin proteins in the breast cancer cells in various groups.Results:Compared with paracancerous normal tissue,the expression levels of CBS and CSE mRNA and proteins in breast cancer tissue were increased(P＜0.05 or P＜0.01).Compared with MDA-MB-231 cells,the CBS mRNA expression level in the MCF-7 cells was increased(P＜0.05);compared with MCF-7 cells,the expression level of CSE protein in the MDA-MB-231 cells was decreased(P＜0.05).Compared with siNC group,the proliferation activity,the numbers of migration and invasion cells,the expression levels of N-cadherin and Vimentin proteins in the MCF-7 cells in siCBS group were significantly decreased(P＜0.05),and the expression level of E-cadherin protein was increased(P＜0.05).Compared with ovNC group,the proliferation activity,the numbers of migratoin and invasion cells,and the expression levels of N-cadherin and Vimentin proteins in the MDA-MB-231 cells in ovCSE group were increased(P＜0.05),while the expression level of E-cadherin protein was significantly decreased(P＜0.05).Conclusion:The expressions of CBS and CSE are upregulated in breast cancer tissue,and high levels of CBS and CSE promote proliferation,migration,invasion and epithelial-mesenchymal transition(EMT)of breast cancer cells.

Objective In this study,we analyzed the transcriptome sequences of Kupffer cells exposed to simulated microgravity for 3 d and conducted biological experiments to determine how microgravity initiates apoptosis in Kupffer cells. Methods Rotary cell culture system was used to construct a simulated microgravity model.GO and KEGG analyses were conducted using the DAVID database.GSEA was performed using the R language.The STRING database was used to conduct PPI analysis.qPCR was used to measure the IL1B,TNFA,CASP3,CASP9,and BCL2L11 mRNA expressions.Western Blotting was performed to detect the level of proteins CASP3 and CASP 9.Flow cytometry was used to detect apoptosis and mitochondrial membrane cells.Transmission electron microscopy was used to detect changes in the ultrastructure of Kupffer cells. Results Transcriptome Sequencing indicated that simulated microgravity affected apoptosis and the inflammatory state of Kupffer cells.Simulated microgravity improved the CASP3,CASP9,and BCL2L11 expressions in Kupffer cells.Annexin-V/PI and JC-1 assays showed that simulated microgravity promoted apoptosis in Kupffer cells.Simulated microgravity causes M1 polarization in Kupffer cells. Conclusion Our study found that simulated microgravity facilitated the apoptosis of Kupffer cells through the mitochondrial pathway and activated Kupffer cells into M1 polarization,which can secrete TNFA to promote apoptosis.

Cardio-oncology is an emerging cross-discipline， which has received extensive attention and rapid development at home and abroad in recent years， while the construction of related disciplines in the field of traditional Chinese medicine （TCM） is still in its initial stage. By sorting out the construction of oncology and cardiology related disciplines at home and abroad at this stage， and clarifying the significance and main research contents of the discipline， it is proposed that the construction of TCM related disciplines should be oriented to the four main aspects， including clinical practice， scientific research， talent training and promotion of cultural characteristics. Therefore， actively carrying out multidisciplinary crossing， cultivating related professional talent team， and forming TCM diagnosis and treatment guidelines or consensus to support clinical practice is the essential foundation for the construction of TCM cardio-oncology discipline. Meanwhile， fully exploring the characteristics and advantages of TCM is the key to the construction process of the discipline， such as writing and summarising and analysing relevant high-quality clinical case reports of TCM for evidence-based optimisation， as well as widely applying the concept of "treating disease before it arises" of TCM characteristics to the clinical prevention and treatment of the relevant diseases and scientific research， etc.， so as to comprehensively guarantee the development of the discipline of TCM cardio-oncology.

AIM: To investigate the interactive effects of blood glucose and blood calcium on the prognostic impact of patients with acute severe pancreatitis (SAP) and to analyze their predictive efficacy on prognosis. METHODS: One hundred and seven patients with SAP admitted to our hospital from September 2019 to October 2022 were selected for the study and were divided into poor and good groups according to their prognosis within 28 d. The blood glucose, blood calcium, modified Marshall score, bedside acute pancreatitis severity score (BISAP) were compared between the two groups before treatment, after 3 d of treatment, and after 7 d of treatment, and the correlation between blood glucose, blood calcium and modified Marshall score and BISAP score was analyzed. The blood glucose levels of patients with different blood calcium were compared. Cox regression was used to analyze the factors associated with prognosis. The presence and type of interaction between blood glucose and blood calcium on prognosis were analyzed using the interaction coefficient γ and relative risk (RR) values. The subject operating characteristic curve (ROC) was used to analyze the predictive efficacy of blood glucose and blood calcium on prognosis. RESULTS: The blood glucose, modified Marshall score, and BISAP score of the adverse group after treatment were higher than those of the good group, while the blood calcium was lower than that of the good group (P<0.05). After 3 and 7 days of treatment, blood glucose was positively correlated with improved Marshall score and BISAP score (P<0.05). The blood glucose level in patients with decreased blood calcium was higher than that in patients with normal blood calcium (P<0.05). The decrease of blood calcium had positive interaction with the increase of blood glucose (P<0.05). After 3 and 7 days of treatment, the AUC of blood glucose combined with blood calcium was greater than that predicted by single index (P< 0.05). CONCLUSION: Blood glucose and blood calcium are related to the severity of the disease in SAP patients. There is an interaction between blood glucose and blood calcium in predicting the prognosis of SAP patients. The combined detection of blood glucose and blood calcium has a certain predictive effect on the prognosis of SAP patients.

Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain and changes in bowel habits. IBS is a multifactorial, stress-sensitive disease. Epigenetic changes include DNA methylation change, histone modification, and differential expressions of microRNA and long non-coding RNA. Explaining the changes in IBS from the perspective of epigenetics could bring new insights for the pathogenesis and treatment of the disease. This article reviewed the progress in research on the epigenetics of IBS.

Objective To analyze the mRNA expression level of lymphoid enhance factor 1 (LEF-1), and to investigate its clinical significance in bone marrow mononuclear cells of patients with chronic myeloid leukemia chronic-phase (CML-CP) after initial diagnosis and chemotherapy, and to analyze its clinical significance. Methods The real-time fluorescence quantitative polymerase chain reaction was used to measure the expression level of LEF-1 gene in 38 CML-CP patients after initial diagnosis and chemotherapy and 20 persons without blood system diseases and neoplastic diseases as normal control. The difference of LEF-1 expression level between the patients and healthy control was compared, and the effect of imatinib on the main molecular response (MMR) was analyzed. Results The expression of LEF-1 mRNA in 38 newly diagnosed patients [0.00214 (0.00020 - 0.02120)] was significantly higher than that in normal controls [0.00101 (0.00009 - 0.00233)] (U= 163.0, P< 0.01). The expression of LEF-1 mRNA in MMR group [0.00107 (0.00010 - 0.00519)] was significantly lower than that in non-MMR group [0.01015 (0.00091 -0.03615)] (U= 25.0, P< 0.01). There was no significant difference in LEF-1 mRNA expression between the normal control group and the MMR group after imatinib treatment (U= 201.0, P> 0.05). The level of LEF-1 mRNA expression of non-MMR group was also higher than that of the normal control group (U= 14.0, P<0.01). The rate of acquiring MMR was significantly higher in high LEF-1 mRNA expression group [84.2 %(16/19)] than that in low expression group [47.4%(9/19)] (χ2=4.209, P<0.01). The time of acquiring MMR was significantly shorter in the high LEF-1 mRNA expression group [(10.0 ± 4.5) months] than that in the low expression group [(14.6 ± 3.8) months] (t= 2.705, P< 0.01). Conclusions LEF-1 may be involved in the occurrence and development of CML, and reflects the tumor burden. It may be one of the indicators to predict the efficacy of imatinib.

Objective To quantitatively analyze the mRNA expression level of lymphoid enhance factor 1 (LEF-1) in bone marrow mononuclear cells of patients with acute myeloid leukemia (AML) at intermediate-risk after initial diagnosis and chemotherapy, and to analyze its clinical significance. Methods The real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to measure the expression level of LEF-1 gene in AML patients at intermediate-risk after initial diagnosis and chemotherapy, and its relationship with effectiveness and survival were analyzed. Results The LEF-1 mRNA level in preliminarily diagnosed patients with AML was significantly higher than that in control arm [0.00519 (0.00015-0.09207) vs. 0.00101 (0.00009-0.00233)], and the difference was statistically significant (u=134.50, P<0.01). The LEF-1 mRNA level in patients after chemotherapy was significantly declines as compared to that in patients before chemotherapy [0.00107 (0.00008 - 0.00744) vs. 0.00519 (0.00015 - 0.09207)], and the difference was statistically significant (u= 317.00, P< 0.01) and LEF-1 mRNA expression level before chemotherapy in complete remission (CR) patients was significantly higher than that in non-CR patients [(0.01108 (0.00164 - 0.09207) vs. 0.00110 (0.00015 - 0.00916)], and the difference was statistically significant (u=19.00, P<0.01). High LEF-1 expression predicted a significantly better overall survival in AML patients with intermediate-risk cytogenetics (χ2= 4.549, P= 0.033). Conclusions LEF-1 may be involved in the development and progression of AML at intermediate-risk patients and is closely related to tumor burden and treatment efficacy. LEF-1 may be a good predictor of better prognosis and a novel target for therapeutic effect.

Objective To investigate the mRNA level of lymphoid enhancing factor-1 ( LEF-1) in bone marrow mononuclear cells after the initial diagnosis and chemotherapy of patients with multiple myeloma (MM) and its clinical significance. Methods The LEF-1 mRNA of target gene in 42 MM patient was detected by real-time fluorescence quantitative polymerase chain reaction (RTQ-PCR), and 20 patients without hematological disease were enrolled as the healthy controls. Results The LEF-1 mRNA median level in previously diagnosed MM patients was significantly higher than that in the healthy controls [0.01068 (0.00017 - 0.14100) vs. 0.00101 (0.00009 - 0.002326)], and the difference was statistically significant (U = 91.00, P< 0.001); The LEF-1 mRNA median level in MM patients after chemotherapy was declined compared with the patients before chemotherapy [0.00011 (0.00001 - 0.01548) vs. 0.01068 (0.00017 -0.14100)], and the difference was statistically significant (U = 343.0, P< 0.001). The LEF-1 mRNA median level of MM patients after chemotherapy in progression of disease (PD) group was higher than that in the non-PD groups [0.08386 (0.00288 - 0.14100) vs. 0.003454 (0.000156 - 0.05660)], and the difference was statistically significant (U = 343.0, P< 0.001). The overall survival (OS) rate in the high LEF-1 expression group was shorter than that in the low LEF-1 expression group for MM patients in the initial diagnosis (47.6%vs. 65.5 %, χ2 = 3.931, P= 0.0414). Conclusion LEF-1 may be involved in the occurrence and development of MM, which has a potential to become an indicator of evaluating the poor prognosis and PD of MM patients, and could be served as a novel therapy target for the treatment of MM.