OBJECTIVE: To explore the effect of acupuncture therapy on dysphagia in patients with Parkinson's disease. METHODS: This randomized controlled study lasted 42 days and included 112 patients with Parkinson's disease and dysphagia. Participants were randomly assigned to the experimental and control groups (56 cases each group) using the completely randomized design, all under routine treatment. The experimental group was given acupuncture therapy. The primary outcome was Penetration-Aspiration Scale (PAS). The secondary outcomes were (1) Standardized Swallowing Assessment (SSA), and (2) nutritional status including body mass index (BMI), serum albumin, prealbumin, and hemoglobin. Adverse events were recorded as safety indicators. RESULTS: One participant quitted the study midway. There were no significant differences in baseline assessment (P>0.05). After treatment, both groups showed significant improvement in PAS, SSA and nutritional status except for BMI of the control group. There were significant differences between the two groups in the PAS for both paste and liquid, SSA (25.18±8.25 vs. 20.84±6.92), BMI (19.97±3.34 kg/m²vs. 21.26 ±2.38 kg/m²), serum albumin (35.16 ±5.29 g/L vs. 37.24 ±3.98 g/L), prealbumin (248.33 ±27.72 mg/L vs. 261.39 ±22.10 mg/L), hemoglobin (119.09±12.53 g/L vs. 126.67±13.97 g/L) (P<0.05). There were no severe adverse events during the study. CONCLUSION: The combination of routine treatment and acupuncture therapy can better improve dysphagia and nutritional status in patients with Parkinson's disease, than routine treatment solely. (registration No. CLINICALTRIAL gov NCT06199323).
Humans ; Parkinson Disease/therapy* ; Deglutition Disorders/physiopathology* ; Acupuncture Therapy/adverse effects* ; Male ; Female ; Aged ; Middle Aged ; Treatment Outcome ; Nutritional Status ; Body Mass Index

Cell models can simulate a variety of life states and disease developments, including single cells, two-dimensional (2D) cell cultures, three-dimensional (3D) multicellular spheroids, and organoids. They are essential tools for addressing complex biochemical questions. With continuous advancements in biological and cellular analysis technologies, in vitro cellular models designed to answer scientific questions have evolved rapidly. Early in vitro models primarily relied on 2D systems, which failed to accurately replicate the complex cellular compositions and microenvironmental interactions observed in vivo, let alone support sophisticated investigations into cellular biological functions. Subsequent improvements in cell culture techniques led to the development of 3D culture-based models, such as cellular spheroids. The advent of pluripotent stem cell technology further advanced the development of organoid systems, which closely mimic human organ development. Compared to traditional 2D models, both 3D cellular models and organoids offer significant advantages, including personalization and enhanced physiological relevance, making them particularly suitable for exploring molecular mechanisms of disease progression, discovering novel cellular and biomolecular functions, and conducting related studies. The imaging analysis of common cellular models primarily employs labeling-based methods for in situ imaging of targeted genes, proteins, and small-molecule metabolites, enabling further research on cell types, states, metabolism, and drug efficacy. However, these approaches have drawbacks such as poor labeling specificity and complex experimental procedures. By using cells as experimental models, mass spectrometry technology combined with morphological analysis can reveal quantitative changes and spatial distributions of various biological substances at the spatiotemporal level, including metabolites, proteins, lipids, peptides, drugs, environmental pollutants, and metals. This allows for the investigation of cell-cell interactions, tumor microenvironments, and cellular bioinformational heterogeneity. The application of these cutting-edge imaging technologies generates vast amounts of cellular data, necessitating the development of rapid, efficient, and highly accurate image data algorithms for precise segmentation and identification of single cells, multi-organelle structures, rare cell subpopulations, and complex cellular morphologies. A critical focus lies in creating deep learning models and algorithms that enhance the accuracy of cellular visualization. At the same time, establishing more robust data integration tools is essential not only for analyzing and interpreting outputs but also for effectively uncovering the biological significance of spatially resolved mass spectrometry data. Developing a cell imaging platform with high versatility, operational stability, and specificity to enable data interoperability will significantly enhance its utility in clinical research, thereby advancing investigations into disease molecular mechanisms and supporting precision diagnostics and therapeutics. In contrast to genomic, transcriptomic, and proteomic information, the metabolome can rapidly respond to external stimuli and cellular physiological changes within a short timeframe. This rapid and precise reflection of ongoing cellular state alterations has positioned spatial metabolomics as a pivotal approach for exploring the molecular mechanisms underlying physiological and pathological processes in cells, tissues, and organisms. In this review, we summarize research on cell imaging based on mass spectrometry technologies, including the selection and preparation of cell models, morphological analysis of cell models, spatial omics techniques based on mass spectrometry, mass cytometry, and their applications. We also discuss the current challenges and propose future directions for development in this field.

AIM:To investigate the role of BRCA2 and CDKN1A interacting protein(BCCIP)in gastric can-cer(GC)and elucidate its mechanism in mediating cisplatin resistance.METHODS:The BCCIP mRNA expression was assessed in GC tissues(n=415)and normal tissues(n=34)using The Cancer Genome Atlas(TCGA)database.In an in-ternal cohort(n=36 for RT-qPCR;n=5 for Western blot;n=30 for immunohistochemistry),BCCIP expression at both mRNA and protein levels was examined in GC tissues and paired adjacent normal tissues.Human GC cell lines AGS and HGC27 were cultured in vitro and treated with cisplatin in a dose(0,2,4,6,8 and 10 μmol/L)-and time(0,6,24 and 48 h)-dependent manner,followed by Western blot analysis of BCCIP expression.Stable BCCIP knockdown cell lines(shRNA#1 and shRNA#2 groups)were generated via lentiviral transfection,with empty vector-transfected cells serving as controls(vector group).Flow cytometry and colony formation assay were performed to evaluate the effects of BCCIP on apoptosis and colony-forming ability of GC cells treated with cisplatin.Western blot was utilized to detect the changes of BCCIP protein expression levels in the cytoplasm and nucleus of GC cells after cisplatin(2.5 and 1.0 μmol/L)treatment,as well as the effects of BCCIP on the expression of DNA damage marker γ-H2AX and apoptosis-related proteins cleaved caspase-9 and cleaved caspase-3,and the activation of checkpoint kinase 1(CHK1)after cisplatin(2.5 and 1.0 μmol/L)treatment.Immunofluorescence was conducted to observe the effect of BCCIP on γ-H2AX expression in GC cells treated with cisplatin(2.5 and 1.0 μmol/L).RESULTS:The BCCIP expression was significantly up-regulated in GC tissues compared with normal tissues(P<0.01).Cisplatin induced up-regulation of BCCIP expression in a dose-and time-depen-dent manner.Knockdown of BCCIP significantly enhanced cisplatin-induced apoptosis(P<0.01)and reduced colony-forming ability(P<0.05)of GC cells.Knockdown of BCCIP promoted the expression of γ-H2AX,but inhibited the activa-tion of CHK1 after cisplatin treatment,with increased protein levels of cleaved caspase-9 and cleaved caspase-3(P<0.01).CONCLUSION:Cisplatin promotes the expression of BCCIP in GC cells.BCCIP confers cisplatin resistance in GC cells by suppressing apoptosis through modulation of DNA damage response pathways.

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

Objective To explore the mechanism by which She-Ti-Zhi-Qiu decoction alleviates allergic rhinitis (AR) through gut microbiota-mediated regulation of T helper cell 17(Th17)/regulatory T cells(Treg) balance and related cytokines. Methods Twenty-eight female SD rats were randomly divided into four groups: the Control group, Model group, STZQ group, and Probiotics group. Except for the Control group, all other groups were sensitized with ovalbumin (OVA) to establish AR models. The Control and Model groups received intragastric administration of normal saline, while the STZQ group was administered She-Ti-Zhi-Qiu Decoction, and Probiotics group received probiotics. After two weeks of continuous intragastric administration, nasal mucosa, serum, peripheral blood, and colon contents were collected. The inflammation of nasal mucosal tissue was assessed via HE staining. 16S rDNA sequencing was used to detect and analyze the structure and content of bacteria in colon contents. Flow cytometry was used to detect the relative proportions of Treg and Th17 cells in peripheral blood. ELISA was used to measure the levels of Th17- and Treg-related cytokines in serum. Results Compared with the Control group, the Model group showed an inflammatory response in nasal mucosal tissue, along with increased IL-17A and IL-17E levels and decreased IL-10 levels. The percentage of Th17 cells in peripheral blood increased, while the percentage of Treg cells decreased. Beneficial bacteria in the intestine were decreased, while pathogenic bacteria were increased. Compared with the Model group, the STZQ group showed lower serum IL-17A and IL-17E levels and higher IL-10 levels. The percentage of Th17 in peripheral blood decreased, while the percentage of Treg increased. There was an increase in beneficial bacteria in the intestine and a decrease in pathogenic bacteria. The changes in the microbiota were correlated with IL-17A, IL-17E, and IL-10 levels. Conclusion She-Ti-Zhi-Qiu decoction can ameliorate the inflammation of AR by regulating gut microbiota and Th17/Treg immune balance.
Animals ; T-Lymphocytes, Regulatory/drug effects* ; Th17 Cells/drug effects* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Rhinitis, Allergic/microbiology* ; Rats ; Cytokines

PURPOSE: Intertrochanteric fractures undergoing proximal femoral nail antirotation (PFNA) surgery are associated with significant hidden blood loss. This study aimed to explore whether intramedullary administration of tranexamic acid (TXA) can reduce bleeding in PFNA surgery for intertrochanteric fractures in elderly individuals. METHODS: A randomized controlled trial was conducted from January 2019 to December 2022. Patients aged over 60 years with intertrochanteric fractures who underwent intramedullary fixation surgery with PFNA were eligible for inclusion and grouped according to random numbers. A total of 249 patients were initially enrolled, of which 83 were randomly allocated to the TXA group and 82 were allocated to the saline group. The TXA group received intramedullary perfusion of TXA after the bone marrow was reamed. The primary outcomes were total peri-operative blood loss and post-operative transfusion rate. The occurrence of adverse events was also recorded. Continuous data was analyzed by unpaired t-test or Mann-Whitney U test, and categorical data was analyzed by Pearson Chi-square test. RESULTS: The total peri-operative blood loss (mL) in the TXA group was significantly lower than that in the saline group (577.23 ± 358.02 vs. 716.89 ± 420.30, p = 0.031). The post-operative transfusion rate was 30.67% in the TXA group and 47.95% in the saline group (p = 0.031). The extent of post-operative deep venous thrombosis and the 3-month mortality rate were similar between the 2 groups. CONCLUSION We observed that intramedullary administration of TXA in PFNA surgery for intertrochanteric fractures in elderly individuals resulted in less peri-operative blood loss and decreased transfusion rate, without any adverse effects, and is, thus, recommended.
Humans ; Tranexamic Acid/administration & dosage* ; Hip Fractures/surgery* ; Male ; Aged ; Female ; Fracture Fixation, Intramedullary/adverse effects* ; Blood Loss, Surgical/prevention & control* ; Antifibrinolytic Agents/administration & dosage* ; Aged, 80 and over ; Bone Nails ; Middle Aged ; Blood Transfusion/statistics & numerical data*

Objective:To study the impact of fluoride exposure through drinking water on the risk of hypertension among residents in Jishan County, Shanxi Province.Methods:From March to April 2023, a cluster sampling method was used to select permanent residents aged ≥18 years and residing for ≥10 years in 12 villages in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province as the survey subjects. A questionnaire survey, physical examination, and morning urinary fluoride level testing were conducted. The least absolute shrinkage and selection operator (Lasso) regression were used to analyze the key influencing factors of hypertension. Restricted cubic spline was used to evaluate the linear relationship between urinary fluoride and hypertension. Logistic regression was used to analyze the impact of urinary fluoride on hypertension.Results:Finally, 2 453 survey subjects were included, aged (62 ± 10) years, including 1 565 patients (63.80%) with hypertension. There were significant differences in the distribution of age, gender, education level, annual household income, body mass index (BMI), and the level and distribution of urinary fluoride between hypertension group and normal blood pressure group ( P < 0.05). The Lasso regression results showed that age, education level, BMI, and urinary fluoride were the key influencing factors of hypertension, with coefficients of 1.04, - 0.12, 0.24 and 0.01, respectively. The results of the restricted cubic spline showed that there was a linear relationship between urinary fluoride and hypertension after adjusting for age, education level, and BMI ( Poverall = 0.018, Pnonlinear = 0.482). The logistic regression results showed that after adjusting for age, education level, and BMI, urinary fluoride > 4.68 mg/L was a risk factor for hypertension ( OR = 1.42, 95% CI: 1.10 - 1.84, P = 0.007). Conclusion:High urinary fluoride is a risk factor for hypertension in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province.

AIM:To investigate the role of BRCA2 and CDKN1A interacting protein(BCCIP)in gastric can-cer(GC)and elucidate its mechanism in mediating cisplatin resistance.METHODS:The BCCIP mRNA expression was assessed in GC tissues(n=415)and normal tissues(n=34)using The Cancer Genome Atlas(TCGA)database.In an in-ternal cohort(n=36 for RT-qPCR;n=5 for Western blot;n=30 for immunohistochemistry),BCCIP expression at both mRNA and protein levels was examined in GC tissues and paired adjacent normal tissues.Human GC cell lines AGS and HGC27 were cultured in vitro and treated with cisplatin in a dose(0,2,4,6,8 and 10 μmol/L)-and time(0,6,24 and 48 h)-dependent manner,followed by Western blot analysis of BCCIP expression.Stable BCCIP knockdown cell lines(shRNA#1 and shRNA#2 groups)were generated via lentiviral transfection,with empty vector-transfected cells serving as controls(vector group).Flow cytometry and colony formation assay were performed to evaluate the effects of BCCIP on apoptosis and colony-forming ability of GC cells treated with cisplatin.Western blot was utilized to detect the changes of BCCIP protein expression levels in the cytoplasm and nucleus of GC cells after cisplatin(2.5 and 1.0 μmol/L)treatment,as well as the effects of BCCIP on the expression of DNA damage marker γ-H2AX and apoptosis-related proteins cleaved caspase-9 and cleaved caspase-3,and the activation of checkpoint kinase 1(CHK1)after cisplatin(2.5 and 1.0 μmol/L)treatment.Immunofluorescence was conducted to observe the effect of BCCIP on γ-H2AX expression in GC cells treated with cisplatin(2.5 and 1.0 μmol/L).RESULTS:The BCCIP expression was significantly up-regulated in GC tissues compared with normal tissues(P<0.01).Cisplatin induced up-regulation of BCCIP expression in a dose-and time-depen-dent manner.Knockdown of BCCIP significantly enhanced cisplatin-induced apoptosis(P<0.01)and reduced colony-forming ability(P<0.05)of GC cells.Knockdown of BCCIP promoted the expression of γ-H2AX,but inhibited the activa-tion of CHK1 after cisplatin treatment,with increased protein levels of cleaved caspase-9 and cleaved caspase-3(P<0.01).CONCLUSION:Cisplatin promotes the expression of BCCIP in GC cells.BCCIP confers cisplatin resistance in GC cells by suppressing apoptosis through modulation of DNA damage response pathways.

Objective:To study the impact of fluoride exposure through drinking water on the risk of hypertension among residents in Jishan County, Shanxi Province.Methods:From March to April 2023, a cluster sampling method was used to select permanent residents aged ≥18 years and residing for ≥10 years in 12 villages in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province as the survey subjects. A questionnaire survey, physical examination, and morning urinary fluoride level testing were conducted. The least absolute shrinkage and selection operator (Lasso) regression were used to analyze the key influencing factors of hypertension. Restricted cubic spline was used to evaluate the linear relationship between urinary fluoride and hypertension. Logistic regression was used to analyze the impact of urinary fluoride on hypertension.Results:Finally, 2 453 survey subjects were included, aged (62 ± 10) years, including 1 565 patients (63.80%) with hypertension. There were significant differences in the distribution of age, gender, education level, annual household income, body mass index (BMI), and the level and distribution of urinary fluoride between hypertension group and normal blood pressure group ( P < 0.05). The Lasso regression results showed that age, education level, BMI, and urinary fluoride were the key influencing factors of hypertension, with coefficients of 1.04, - 0.12, 0.24 and 0.01, respectively. The results of the restricted cubic spline showed that there was a linear relationship between urinary fluoride and hypertension after adjusting for age, education level, and BMI ( Poverall = 0.018, Pnonlinear = 0.482). The logistic regression results showed that after adjusting for age, education level, and BMI, urinary fluoride > 4.68 mg/L was a risk factor for hypertension ( OR = 1.42, 95% CI: 1.10 - 1.84, P = 0.007). Conclusion:High urinary fluoride is a risk factor for hypertension in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province.

Objective To investigate the antigen presentation characteristics of dendritic cells(DC)and B cells in cardiac grafts.Methods The heart of BALB/c mice was transplanted into the abdominal cavity of C57BL/6J mice.CD45+cells in the heart graft were extracted and sorted by flow cytometry at postoperative 5 d,and single cell RNA sequencing was performed.Taking DC and B cell subsets in cardiac grafts as the main study cells,the changing trend,antigen presenting ability and intercellular communication with T cells after heart transplantation were analyzed by bioinformatics analysis and flow cytometry.Gene ontology(GO)function enrichment difference analysis was adopted to prove the specific function and the reliability annotation of cell subsets.Results Germinal center-like B cell(GC-L B)was the B cell subset with the largest increase in quantity during the acute rejection phase,accounting for 87％.Classical DC(cDC)2 was the only DC subset with a significant increase in quantity during acute rejection of heart transplantation,accounting for 44％of DC subset,and it occupied the highest communication intensity with T cells after heart transplantation.Mononucleated DC(moDC)and memory B cell(MBC)were the main transmitters of T cell input signals in non-transplanted hearts,whereas transformed into cDC2 and GC-L B during the acute rejection phase.Among them,MBC and GC-L B were the main sources of T cell input signals in non-transplanted hearts and heart grafts.Conclusions Compared with DC,B cells occupy a higher number and weight in the intercellular communication with T cells in non-transplanted hearts and heart grafts,prompting that the antigen presenting activity of B cells is more active and stronger than DC in the early stage of acute rejection of heart transplantation.