Pub Date : 2026-02-06DOI: 10.1097/MD.0000000000047277
Xuchen Meng, Weijie Zhong, Dingzhong Tang, Zixian Mei, Lin Zhu, Tanjun Deng, Xin Lv, Jiexi Xiao, Yueqi Zhu, Yi Li
Acute ischemic stroke (AIS) is a leading cause of mortality and long-term disability worldwide. The identification of reliable prognostic determinants and formation of a validated model for AIS is unclear. We retrospectively recruited 210 patients with stroke of anterior circulation large-vessel occlusion who underwent endovascular thrombectomy between March 2021 and March 2024. Participants were aged 18 years or older and had undergone examination and treatment for at least 90 days. We collected baseline demographic characteristics, medical records, and blood biomarkers and tracked the prognosis for 30 days. We used LASSO-logistic regression to identify potential indicators of AIS over a 90 days. After adjusting for age (P = .130), previous stroke or transient ischemic attack (P = .112), admission diastolic pressure (P = .101), glucose (P = .162), and albumin (P = .094), only male (vs female, P = .042), alcohol consumption (P = .013), hypertension (P = .007), trial of acute stroke treatment type "others" versus large artery atherosclerosis, P = .046), leukocytes (P = .013), and neutrophil-to-lymphocyte ratio (P < .001) remained significant predictors of poor clinical endpoints. The prognostic model had a classification accuracy of 77.6%, a sensitivity of 79.3%, a specificity of 73.3%, and a precision of 88.1%. This study identified modifiable risk factors such as alcohol consumption and hypertension, along with inflammatory markers such as leukocyte count and neutrophil-to-lymphocyte ratio, as significant predictors of poor outcomes in patients with AIS undergoing endovascular thrombectomy. These findings could guide clinicians in identifying high-risk patients and in tailoring treatment strategies. Further studies are needed to validate these predictors and to explore their potential roles in therapeutic interventions.
{"title":"Predicting the prognosis of acute ischemic stroke patients undergoing endovascular thrombectomy: A multicenter retrospective study.","authors":"Xuchen Meng, Weijie Zhong, Dingzhong Tang, Zixian Mei, Lin Zhu, Tanjun Deng, Xin Lv, Jiexi Xiao, Yueqi Zhu, Yi Li","doi":"10.1097/MD.0000000000047277","DOIUrl":"10.1097/MD.0000000000047277","url":null,"abstract":"<p><p>Acute ischemic stroke (AIS) is a leading cause of mortality and long-term disability worldwide. The identification of reliable prognostic determinants and formation of a validated model for AIS is unclear. We retrospectively recruited 210 patients with stroke of anterior circulation large-vessel occlusion who underwent endovascular thrombectomy between March 2021 and March 2024. Participants were aged 18 years or older and had undergone examination and treatment for at least 90 days. We collected baseline demographic characteristics, medical records, and blood biomarkers and tracked the prognosis for 30 days. We used LASSO-logistic regression to identify potential indicators of AIS over a 90 days. After adjusting for age (P = .130), previous stroke or transient ischemic attack (P = .112), admission diastolic pressure (P = .101), glucose (P = .162), and albumin (P = .094), only male (vs female, P = .042), alcohol consumption (P = .013), hypertension (P = .007), trial of acute stroke treatment type \"others\" versus large artery atherosclerosis, P = .046), leukocytes (P = .013), and neutrophil-to-lymphocyte ratio (P < .001) remained significant predictors of poor clinical endpoints. The prognostic model had a classification accuracy of 77.6%, a sensitivity of 79.3%, a specificity of 73.3%, and a precision of 88.1%. This study identified modifiable risk factors such as alcohol consumption and hypertension, along with inflammatory markers such as leukocyte count and neutrophil-to-lymphocyte ratio, as significant predictors of poor outcomes in patients with AIS undergoing endovascular thrombectomy. These findings could guide clinicians in identifying high-risk patients and in tailoring treatment strategies. Further studies are needed to validate these predictors and to explore their potential roles in therapeutic interventions.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 6","pages":"e47277"},"PeriodicalIF":1.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1097/MD.0000000000047497
Yonghao Li, Zheng Shu, Chenyu Sun, Scott Lowe, Rachel Bentley, Yaru Li, Bethany King, Shuya Chen, Qin Zhou, Mei Zhang
NF-κB activating protein (NKAP) plays important roles in various cancers, including breast cancer. However, its expression and prognosis value in breast cancer remains uncertain. Gene expression profiling interactive analysis, Human protein atlas database, and University of Alabama at Birmingham Cancer data analysis portal database were used to predict the expression and prognostic value of NKAP in breast cancer. Immunohistochemistry, quantitative real time polymerase chain reaction (qRT-PCR) and western blot were performed to detect NKAP expression. The effects of NKAP on cell proliferation, migration and drug sensitivity were investigated in MDA-MB-231 and SK-BR-3 cells. NKAP protein expression differed in breast cancer tissues and paraneoplastic tissues based on the cancer genome atlas data. The high NKAP expression was significantly correlated with a poor prognosis in breast cancer patients. The results of immunohistochemistry, western blot assay, and qRT-PCR proved that NKAP was highly expressed in breast cancer tissues compared with paraneoplastic tissues. In addition, qRT-PCR results showed that high expression of NKAP was significantly correlated with the larger tumor size and higher TNM stage. Moreover, knockdown of NKAP significantly inhibited the proliferation, migration, and enhanced drug sensitivity of MDA-MB-231 and SK-BR-3 cells. NKAP is highly expressed in breast cancer tissues, and its high expression is closely associated with poor prognosis. NKAP also promotes proliferation, migration, and inhibits drug sensitivity of breast cancer cells.
{"title":"High NKAP expression predicts poor prognosis of breast cancer patients.","authors":"Yonghao Li, Zheng Shu, Chenyu Sun, Scott Lowe, Rachel Bentley, Yaru Li, Bethany King, Shuya Chen, Qin Zhou, Mei Zhang","doi":"10.1097/MD.0000000000047497","DOIUrl":"10.1097/MD.0000000000047497","url":null,"abstract":"<p><p>NF-κB activating protein (NKAP) plays important roles in various cancers, including breast cancer. However, its expression and prognosis value in breast cancer remains uncertain. Gene expression profiling interactive analysis, Human protein atlas database, and University of Alabama at Birmingham Cancer data analysis portal database were used to predict the expression and prognostic value of NKAP in breast cancer. Immunohistochemistry, quantitative real time polymerase chain reaction (qRT-PCR) and western blot were performed to detect NKAP expression. The effects of NKAP on cell proliferation, migration and drug sensitivity were investigated in MDA-MB-231 and SK-BR-3 cells. NKAP protein expression differed in breast cancer tissues and paraneoplastic tissues based on the cancer genome atlas data. The high NKAP expression was significantly correlated with a poor prognosis in breast cancer patients. The results of immunohistochemistry, western blot assay, and qRT-PCR proved that NKAP was highly expressed in breast cancer tissues compared with paraneoplastic tissues. In addition, qRT-PCR results showed that high expression of NKAP was significantly correlated with the larger tumor size and higher TNM stage. Moreover, knockdown of NKAP significantly inhibited the proliferation, migration, and enhanced drug sensitivity of MDA-MB-231 and SK-BR-3 cells. NKAP is highly expressed in breast cancer tissues, and its high expression is closely associated with poor prognosis. NKAP also promotes proliferation, migration, and inhibits drug sensitivity of breast cancer cells.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 6","pages":"e47497"},"PeriodicalIF":1.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1097/MD.0000000000047491
Muhammet Fatih Keyif, Ferdi Bolat
Accurate severity assessment is crucial in acute cholecystitis, yet commonly used inflammatory markers such as C-reactive protein, white blood cell count, and bilirubin have limited predictive accuracy. The triglyceride-glucose (TyG) index has emerged as a potential biomarker reflecting metabolic stress and inflammation. This retrospective observational study included 134 patients admitted with acute cholecystitis between 2020 and 2024. Disease severity was classified according to the Tokyo Guidelines 2018, and patients were grouped as non-severe (mild-moderate) or severe. Laboratory parameters obtained at admission were analyzed, and the TyG index was calculated as ln (fasting triglyceride × fasting glucose/2). Univariate and multivariable logistic regression analyses and receiver operating characteristic curve analysis were performed. Of the 134 patients, 26 (19.4%) had severe acute cholecystitis. Median fasting glucose (P = .031) and TyG index values (P = .029) were higher in the severe group, while triglycerides, C-reactive protein, white blood cell count, and bilirubin showed no significant differences. The TyG index was associated with severe disease in univariate analysis (odds ratio: 1.62; 95% confidence interval: 1.05-2.49; P = .028), but not after multivariable adjustment (P = .17). Receiver operating characteristic analysis demonstrated an area under the curve of 0.79 (95% confidence interval: 0.71-0.87; P < .001), with an optimal cutoff value of 8.8 (65% sensitivity, 80% specificity). The TyG index was higher in patients with severe acute cholecystitis and demonstrated moderate diagnostic performance. Although not independently associated with disease severity after adjustment, it may serve as an adjunctive marker for early risk stratification, warranting further prospective validation.
{"title":"Assessing the role of the triglyceride-glucose index in the diagnosis and risk stratification of acute cholecystitis: A retrospective study.","authors":"Muhammet Fatih Keyif, Ferdi Bolat","doi":"10.1097/MD.0000000000047491","DOIUrl":"10.1097/MD.0000000000047491","url":null,"abstract":"<p><p>Accurate severity assessment is crucial in acute cholecystitis, yet commonly used inflammatory markers such as C-reactive protein, white blood cell count, and bilirubin have limited predictive accuracy. The triglyceride-glucose (TyG) index has emerged as a potential biomarker reflecting metabolic stress and inflammation. This retrospective observational study included 134 patients admitted with acute cholecystitis between 2020 and 2024. Disease severity was classified according to the Tokyo Guidelines 2018, and patients were grouped as non-severe (mild-moderate) or severe. Laboratory parameters obtained at admission were analyzed, and the TyG index was calculated as ln (fasting triglyceride × fasting glucose/2). Univariate and multivariable logistic regression analyses and receiver operating characteristic curve analysis were performed. Of the 134 patients, 26 (19.4%) had severe acute cholecystitis. Median fasting glucose (P = .031) and TyG index values (P = .029) were higher in the severe group, while triglycerides, C-reactive protein, white blood cell count, and bilirubin showed no significant differences. The TyG index was associated with severe disease in univariate analysis (odds ratio: 1.62; 95% confidence interval: 1.05-2.49; P = .028), but not after multivariable adjustment (P = .17). Receiver operating characteristic analysis demonstrated an area under the curve of 0.79 (95% confidence interval: 0.71-0.87; P < .001), with an optimal cutoff value of 8.8 (65% sensitivity, 80% specificity). The TyG index was higher in patients with severe acute cholecystitis and demonstrated moderate diagnostic performance. Although not independently associated with disease severity after adjustment, it may serve as an adjunctive marker for early risk stratification, warranting further prospective validation.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 6","pages":"e47491"},"PeriodicalIF":1.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1097/MD.0000000000047549
Liang Dou
Background: Research exploring how aerobic exercise influences cardiopulmonary function has gained prominence within health sciences in recent years. However, systematic analyses examining this research area remain limited, highlighting the need for bibliometric approaches to clarify the current research status and emerging trends.
Methods: This study reviewed publications from 2010 to 2024 to comprehensively outline progress and identify future directions within this field. Bibliometric analysis and visualization were performed using CiteSpace 6.4.R1, examining publication trends, geographic distributions, institutional contributions, author collaboration networks, key cited references, and keyword co-occurrences.
Results: The research focus has evolved from traditional endurance training toward innovative methods, such as high-intensity interval training. This shift underscores aerobic exercise's significant role in enhancing cardiopulmonary fitness, preventing metabolic diseases, supporting cardiovascular rehabilitation, and improving psychological health. Keyword analysis further revealed growing research interests in molecular mechanisms, personalized interventions, and interdisciplinary approaches.
Conclusion: Research from 2010 to 2024 has expanded our theoretical understanding of aerobic exercise's effects on cardiopulmonary function and provided valuable evidence for health policy development and clinical practice. Future studies should further investigate underlying molecular mechanisms, personalized intervention strategies, and multidisciplinary collaboration to advance and broaden the scope of this important field.
{"title":"The impact of aerobic exercise on cardiopulmonary function: A bibliometric and visualization analysis.","authors":"Liang Dou","doi":"10.1097/MD.0000000000047549","DOIUrl":"10.1097/MD.0000000000047549","url":null,"abstract":"<p><strong>Background: </strong>Research exploring how aerobic exercise influences cardiopulmonary function has gained prominence within health sciences in recent years. However, systematic analyses examining this research area remain limited, highlighting the need for bibliometric approaches to clarify the current research status and emerging trends.</p><p><strong>Methods: </strong>This study reviewed publications from 2010 to 2024 to comprehensively outline progress and identify future directions within this field. Bibliometric analysis and visualization were performed using CiteSpace 6.4.R1, examining publication trends, geographic distributions, institutional contributions, author collaboration networks, key cited references, and keyword co-occurrences.</p><p><strong>Results: </strong>The research focus has evolved from traditional endurance training toward innovative methods, such as high-intensity interval training. This shift underscores aerobic exercise's significant role in enhancing cardiopulmonary fitness, preventing metabolic diseases, supporting cardiovascular rehabilitation, and improving psychological health. Keyword analysis further revealed growing research interests in molecular mechanisms, personalized interventions, and interdisciplinary approaches.</p><p><strong>Conclusion: </strong>Research from 2010 to 2024 has expanded our theoretical understanding of aerobic exercise's effects on cardiopulmonary function and provided valuable evidence for health policy development and clinical practice. Future studies should further investigate underlying molecular mechanisms, personalized intervention strategies, and multidisciplinary collaboration to advance and broaden the scope of this important field.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 6","pages":"e47549"},"PeriodicalIF":1.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1097/MD.0000000000047451
Luo Zhao, Jia He, Zhijun Han, Yisheng Zhang, Li Li
The complexity of diagnostic and therapeutic decision-making in esophageal cancer underscores the need for effective teaching strategies to enhance clinical reasoning skills. This study evaluated the association of a problem-based learning (PBL) approach with clinical reasoning ability, theoretical knowledge acquisition, and learning perceptions among medical interns. In this retrospective study, 132 medical interns completing thoracic surgery rotations were included. A control group (n = 64) taught via conventional lectures was compared to an observation group (n = 68) instructed using structured PBL modules. Baseline comparability was confirmed. Outcomes included standardized assessments of clinical reasoning performance, diagnostic accuracy, differential diagnosis formulation, and case presentation quality. Theoretical knowledge was tested via written examinations, and self-evaluation questionnaires assessed perceived learning gains. Data were analyzed using Welch Student t test, Mann-Whitney U test, and Chi-square tests, with P < .05 considered significant. Compared to the control group, the PBL group demonstrated a higher overall clinical reasoning score (87.4 ± 6.3 vs 79.1 ± 7.2; t = 7.059, P < .001) and greater diagnostic accuracy (92.6% vs 68.8%; χ2 = 12.264, P = .001). The PBL approach was also associated with superior theoretical knowledge scores (85.7 ± 5.9 vs 81.0 ± 6.6; t = 4.319, P < .001) and higher sub-domain scores in pathophysiology, diagnostic interpretation, and treatment principles (all P < .01). Student self-assessments indicated higher satisfaction, stronger self-reported critical thinking, and greater perceived integrative ability in the PBL cohort (all P < .001). The structured PBL model was significantly associated with improved clinical reasoning, theoretical knowledge, and self-perceived competence in esophageal cancer education. These findings suggest the potential value of integrating PBL into competency-based medical training for complex oncological diseases.
{"title":"Impact of problem-based learning on the development of clinical reasoning skills in esophageal cancer teaching.","authors":"Luo Zhao, Jia He, Zhijun Han, Yisheng Zhang, Li Li","doi":"10.1097/MD.0000000000047451","DOIUrl":"10.1097/MD.0000000000047451","url":null,"abstract":"<p><p>The complexity of diagnostic and therapeutic decision-making in esophageal cancer underscores the need for effective teaching strategies to enhance clinical reasoning skills. This study evaluated the association of a problem-based learning (PBL) approach with clinical reasoning ability, theoretical knowledge acquisition, and learning perceptions among medical interns. In this retrospective study, 132 medical interns completing thoracic surgery rotations were included. A control group (n = 64) taught via conventional lectures was compared to an observation group (n = 68) instructed using structured PBL modules. Baseline comparability was confirmed. Outcomes included standardized assessments of clinical reasoning performance, diagnostic accuracy, differential diagnosis formulation, and case presentation quality. Theoretical knowledge was tested via written examinations, and self-evaluation questionnaires assessed perceived learning gains. Data were analyzed using Welch Student t test, Mann-Whitney U test, and Chi-square tests, with P < .05 considered significant. Compared to the control group, the PBL group demonstrated a higher overall clinical reasoning score (87.4 ± 6.3 vs 79.1 ± 7.2; t = 7.059, P < .001) and greater diagnostic accuracy (92.6% vs 68.8%; χ2 = 12.264, P = .001). The PBL approach was also associated with superior theoretical knowledge scores (85.7 ± 5.9 vs 81.0 ± 6.6; t = 4.319, P < .001) and higher sub-domain scores in pathophysiology, diagnostic interpretation, and treatment principles (all P < .01). Student self-assessments indicated higher satisfaction, stronger self-reported critical thinking, and greater perceived integrative ability in the PBL cohort (all P < .001). The structured PBL model was significantly associated with improved clinical reasoning, theoretical knowledge, and self-perceived competence in esophageal cancer education. These findings suggest the potential value of integrating PBL into competency-based medical training for complex oncological diseases.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 6","pages":"e47451"},"PeriodicalIF":1.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1097/MD.0000000000047440
Liwen Huang, Xue Li, Yao Hao, Bo Huang, Chengbin Pei, Xiuying Pei, Qian Zhang, Guodong Chen, Shuya Zhang
Emerging evidence suggests that gut microbiota composition influences male reproductive health; however, the immunometabolic mechanisms underlying this association remain insufficiently characterized. We investigated whether specific immune cell-mediated metabolic pathways, particularly plasmacytoid dendritic cell (pDC)-driven L-glutamate catabolism via the hydroxyglutarate pathway, contribute to the causal link between gut microbiota and male infertility. We conducted a 2-sample, 2-step Mendelian randomization (MR) analysis using inverse-variance weighting as the primary estimator and Bayesian weighted MR for robustness. Exposure data comprised 412 gut microbial taxa/metabolic pathways and 731 immune cell phenotypes from large European-ancestry genome-wide association studies. Male infertility genome-wide association studies data (1429 cases; 128,710 controls) were obtained from FinnGen R10. Only exposure-mediator-outcome pairs meeting stringent pleiotropy, heterogeneity, and reverse-causality criteria were retained for mediation analysis. Nine microbial taxa/metabolic pathways and 18 immune traits exhibited putative causal associations with male infertility. The L-glutamate degradation V pathway via hydroxyglutarate was linked to reduced infertility risk (inverse-variance weighting odds ratio [OR] = 0.68; 95% confidence interval, 0.52-0.89; P = .005). Two-step MR suggested that forward scatter area on pDCs may mediate this association, although the mediation effect was imprecise (effect = 0.0277; 95% confidence interval, -0.0348 to 0.0903). This study provides suggestive genetic evidence that pDC-mediated glutamate catabolism may connect gut microbial metabolic activity to male infertility. These findings highlight immunometabolic pathways as testable targets for mechanistic validation and microbiota-directed interventions.
{"title":"Plasmacytoid dendritic cell-mediated L-glutamate catabolism links gut microbiota to male infertility.","authors":"Liwen Huang, Xue Li, Yao Hao, Bo Huang, Chengbin Pei, Xiuying Pei, Qian Zhang, Guodong Chen, Shuya Zhang","doi":"10.1097/MD.0000000000047440","DOIUrl":"10.1097/MD.0000000000047440","url":null,"abstract":"<p><p>Emerging evidence suggests that gut microbiota composition influences male reproductive health; however, the immunometabolic mechanisms underlying this association remain insufficiently characterized. We investigated whether specific immune cell-mediated metabolic pathways, particularly plasmacytoid dendritic cell (pDC)-driven L-glutamate catabolism via the hydroxyglutarate pathway, contribute to the causal link between gut microbiota and male infertility. We conducted a 2-sample, 2-step Mendelian randomization (MR) analysis using inverse-variance weighting as the primary estimator and Bayesian weighted MR for robustness. Exposure data comprised 412 gut microbial taxa/metabolic pathways and 731 immune cell phenotypes from large European-ancestry genome-wide association studies. Male infertility genome-wide association studies data (1429 cases; 128,710 controls) were obtained from FinnGen R10. Only exposure-mediator-outcome pairs meeting stringent pleiotropy, heterogeneity, and reverse-causality criteria were retained for mediation analysis. Nine microbial taxa/metabolic pathways and 18 immune traits exhibited putative causal associations with male infertility. The L-glutamate degradation V pathway via hydroxyglutarate was linked to reduced infertility risk (inverse-variance weighting odds ratio [OR] = 0.68; 95% confidence interval, 0.52-0.89; P = .005). Two-step MR suggested that forward scatter area on pDCs may mediate this association, although the mediation effect was imprecise (effect = 0.0277; 95% confidence interval, -0.0348 to 0.0903). This study provides suggestive genetic evidence that pDC-mediated glutamate catabolism may connect gut microbial metabolic activity to male infertility. These findings highlight immunometabolic pathways as testable targets for mechanistic validation and microbiota-directed interventions.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 6","pages":"e47440"},"PeriodicalIF":1.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Constipation is a common gastrointestinal disorder associated with impaired motility, inflammation, and altered neuro-intestinal regulation. Taohe Chengqi Decoction, a classical prescription from Shang Han Lun, has been widely applied in the treatment of constipation, yet its pharmacological mechanisms remain insufficiently understood. We integrated systems pharmacology and network analysis to elucidate the therapeutic mechanisms of Taohe Chengqi Decoction against constipation. Active compounds and their putative targets were retrieved from traditional Chinese medicine systems pharmacology and PubChem, while constipation-related genes were collected from GeneCards and OMIM. Shared targets were identified and subsequently analyzed using STRING to construct a protein-protein interaction network. Hub proteins were ranked by degree centrality. A drug-disease-target network was built to map the interactions between Taohe Chengqi Decoction and constipation. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed to uncover functional modules and signaling pathways. A total of 188 common targets were identified. Protein-protein interaction network analysis highlighted AKT1, interleukin-6 (IL6), IL1B, and JUN as hub proteins, suggesting central roles in regulating inflammation, apoptosis, and signal transduction. Additional nodes with high connectivity, such as caspase-3, PTGS2, signal transducer and activator of transcription 3, hypoxia-inducible factor-1α, estrogen receptor 1, and epidermal growth factor receptor, were implicated in apoptosis, oxidative stress, and transcriptional regulation. The drug-disease-target network revealed a dense and highly interconnected structure, reflecting the multicomponent, multi-target nature of Taohe Chengqi Decoction. Kyoto encyclopedia of genes and genomes enrichment indicated significant involvement of the advanced glycation end-product binding to their receptor signaling pathway, along with IL-17, TNF, and HIF-1 pathways, underscoring the contribution of inflammatory and oxidative stress-related processes. This study, based on computational pharmacology analysis, predicts that Taohe Chengqi Decoction may exert therapeutic effects on constipation through an integrated regulation involving multiple components, targets, and pathways. The potential mechanisms are likely associated with the modulation of inflammatory responses, apoptosis, and oxidative stress, with the advanced glycation end-product binding to their receptor signaling pathway possibly acting as a key mediator. These findings provide theoretical insights and future directions for elucidating the molecular mechanisms underlying the therapeutic effects of Taohe Chengqi Decoction against constipation.
{"title":"Network pharmacology insights into the mechanistic basis of Taohe Chengqi Decoction in the treatment of constipation.","authors":"Yulai Yin, Yixuan Xie, Shufa Tan, Yinxu Zhang, Chen Xu","doi":"10.1097/MD.0000000000047501","DOIUrl":"10.1097/MD.0000000000047501","url":null,"abstract":"<p><p>Constipation is a common gastrointestinal disorder associated with impaired motility, inflammation, and altered neuro-intestinal regulation. Taohe Chengqi Decoction, a classical prescription from Shang Han Lun, has been widely applied in the treatment of constipation, yet its pharmacological mechanisms remain insufficiently understood. We integrated systems pharmacology and network analysis to elucidate the therapeutic mechanisms of Taohe Chengqi Decoction against constipation. Active compounds and their putative targets were retrieved from traditional Chinese medicine systems pharmacology and PubChem, while constipation-related genes were collected from GeneCards and OMIM. Shared targets were identified and subsequently analyzed using STRING to construct a protein-protein interaction network. Hub proteins were ranked by degree centrality. A drug-disease-target network was built to map the interactions between Taohe Chengqi Decoction and constipation. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed to uncover functional modules and signaling pathways. A total of 188 common targets were identified. Protein-protein interaction network analysis highlighted AKT1, interleukin-6 (IL6), IL1B, and JUN as hub proteins, suggesting central roles in regulating inflammation, apoptosis, and signal transduction. Additional nodes with high connectivity, such as caspase-3, PTGS2, signal transducer and activator of transcription 3, hypoxia-inducible factor-1α, estrogen receptor 1, and epidermal growth factor receptor, were implicated in apoptosis, oxidative stress, and transcriptional regulation. The drug-disease-target network revealed a dense and highly interconnected structure, reflecting the multicomponent, multi-target nature of Taohe Chengqi Decoction. Kyoto encyclopedia of genes and genomes enrichment indicated significant involvement of the advanced glycation end-product binding to their receptor signaling pathway, along with IL-17, TNF, and HIF-1 pathways, underscoring the contribution of inflammatory and oxidative stress-related processes. This study, based on computational pharmacology analysis, predicts that Taohe Chengqi Decoction may exert therapeutic effects on constipation through an integrated regulation involving multiple components, targets, and pathways. The potential mechanisms are likely associated with the modulation of inflammatory responses, apoptosis, and oxidative stress, with the advanced glycation end-product binding to their receptor signaling pathway possibly acting as a key mediator. These findings provide theoretical insights and future directions for elucidating the molecular mechanisms underlying the therapeutic effects of Taohe Chengqi Decoction against constipation.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 6","pages":"e47501"},"PeriodicalIF":1.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1097/MD.0000000000047610
Ji Yang, Shuning Zhang, Jian Liu, Lin Xin, Shijian Cao
The co-occurrence of rheumatoid arthritis (RA) and cerebral infarction is highly prevalent in clinical practice. While integrated traditional Chinese medicine (TCM) and Western medicine offers unique advantages in treatment, the objective indicators associated with TCM syndromes in this specific patient population remain unclear, hindering precise syndrome differentiation. This study, utilizing a screened cohort from 920 hospitalized patients with RA and cerebral infarction, aimed to address this research gap. Based on strict inclusion, exclusion, and elimination criteria, 142 patients were selected from the initial 920. The distribution of TCM syndromes and their associated influencing factors were analyzed using the Kolmogorov-Smirnov test, Brown-Forsythe ANOVA, the chi-square test, as well as both binary and multinomial logistic regression (employed complementarily to overcome the sample size limitations of less common syndromes). First, among the quantitative indicators, only hemoglobin (Hb) level showed significant differences between groups. The Hb level in the wind-cold obstruction syndrome was significantly higher than that in the dampness-heat obstruction syndrome (P = .007) and the phlegm-stasis obstruction syndrome (P = .029). Second, glucose-6-phosphate isomerase, anti-keratin antibody, and anti-cyclic citrullinated peptide IgG were significantly associated with TCM syndromes (P < .05). Specifically, they were identified as independent risk factors for dampness-heat obstruction syndrome (OR = 2.611, 2.218), while also serving as independent protective factors for liver-kidney deficiency syndrome relative to phlegm-stasis obstruction syndrome (OR = 0.294, 0.350). Within the studied population from East China, glucose-6-phosphate isomerase, anti-keratin antibody, anti-cyclic citrullinated peptide IgG, and Hb show associations with TCM syndrome differentiation in patients with RA complicated by cerebral infarction, particularly for the dominant damp-heat obstruction syndrome. The rigorous screening process enhances the reliability of the conclusions for the major syndromes studied, providing a preliminary evidence-based foundation for objective syndrome differentiation in this specific clinical context. Further multi-center studies with larger samples, especially of rare syndrome types, are needed to validate and generalize these findings.
{"title":"Objective TCM syndrome differentiation in rheumatoid arthritis patients with cerebral infarction: The auxiliary diagnostic value of autoantibodies (anti-CCP IgG, AKA, and GPI) and hemoglobin.","authors":"Ji Yang, Shuning Zhang, Jian Liu, Lin Xin, Shijian Cao","doi":"10.1097/MD.0000000000047610","DOIUrl":"10.1097/MD.0000000000047610","url":null,"abstract":"<p><p>The co-occurrence of rheumatoid arthritis (RA) and cerebral infarction is highly prevalent in clinical practice. While integrated traditional Chinese medicine (TCM) and Western medicine offers unique advantages in treatment, the objective indicators associated with TCM syndromes in this specific patient population remain unclear, hindering precise syndrome differentiation. This study, utilizing a screened cohort from 920 hospitalized patients with RA and cerebral infarction, aimed to address this research gap. Based on strict inclusion, exclusion, and elimination criteria, 142 patients were selected from the initial 920. The distribution of TCM syndromes and their associated influencing factors were analyzed using the Kolmogorov-Smirnov test, Brown-Forsythe ANOVA, the chi-square test, as well as both binary and multinomial logistic regression (employed complementarily to overcome the sample size limitations of less common syndromes). First, among the quantitative indicators, only hemoglobin (Hb) level showed significant differences between groups. The Hb level in the wind-cold obstruction syndrome was significantly higher than that in the dampness-heat obstruction syndrome (P = .007) and the phlegm-stasis obstruction syndrome (P = .029). Second, glucose-6-phosphate isomerase, anti-keratin antibody, and anti-cyclic citrullinated peptide IgG were significantly associated with TCM syndromes (P < .05). Specifically, they were identified as independent risk factors for dampness-heat obstruction syndrome (OR = 2.611, 2.218), while also serving as independent protective factors for liver-kidney deficiency syndrome relative to phlegm-stasis obstruction syndrome (OR = 0.294, 0.350). Within the studied population from East China, glucose-6-phosphate isomerase, anti-keratin antibody, anti-cyclic citrullinated peptide IgG, and Hb show associations with TCM syndrome differentiation in patients with RA complicated by cerebral infarction, particularly for the dominant damp-heat obstruction syndrome. The rigorous screening process enhances the reliability of the conclusions for the major syndromes studied, providing a preliminary evidence-based foundation for objective syndrome differentiation in this specific clinical context. Further multi-center studies with larger samples, especially of rare syndrome types, are needed to validate and generalize these findings.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 6","pages":"e47610"},"PeriodicalIF":1.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1097/MD.0000000000047457
Xinran Cui, Weijie Zhai, Zixun Wang, Yanjiao Xu, Dongyao Fan, Qi Zhang, Li Sun
Some observational studies have suggested that lower pulmonary function increases the risk of cognitive decline or dementia; however, the evidence remains inconclusive. We performed 2-sample Mendelian randomization (MR) analyses to investigate the potential associations between forced vital capacity (FVC) and a range of dementia- and cognition-related outcomes. FVC was selected as the primary indicator of pulmonary function because it is less effort- and cognition-dependent and better reflects overall lung capacity. Outcomes included 6 dementia types: all-cause dementia, Alzheimer disease (AD), dementia with lewy bodies, Parkinson disease dementia, frontotemporal dementia, and vascular dementia, and 6 cognitive domains, including intelligence, fluid intelligence (reasoning and problem-solving ability independent of acquired knowledge), cognitive performance, numeric memory, executive function, and prospective memory. All genetic associations were reported per 1-standard-deviation increase in genetically predicted FVC - expressed as log-odds ratios (log-ORs) for dementia outcomes and standard-deviation changes for cognitive outcomes. The inverse-variance weighted method was used as the primary analysis, complemented by MR-Egger, weighted median, weighted mode, simple mode and MR-PRESSO for sensitivity analyses. False discovery rate (FDR) correction, colocalization, and reverse MR analyses were also performed. This study provides genetic evidence supporting an association between reduced pulmonary function and cognitive impairment. Further studies are needed to clarify the underlying mechanisms. Higher genetically predicted FVC was associated with a lower risk of AD (log-OR per 1-SD increase = -0.24; P = .002; FDR-adjusted P = .011). An inverse association was also observed with all-cause dementia (log-OR per 1-SD increase = -0.37; P = .031), but it did not remain significant after FDR correction (FDR-adjusted P = .094). No significant associations were observed for other dementia subtypes or cognitive outcomes. The results were robust in sensitivity analyses, with no significant findings in reverse MR. Colocalization analysis did not support shared causal variants between FVC and AD (PP.H4.abf <0.75).
一些观察性研究表明,肺功能低下会增加认知能力下降或痴呆的风险;然而,证据仍然没有定论。我们进行了两样本孟德尔随机化(MR)分析,以调查用力肺活量(FVC)与一系列痴呆和认知相关结果之间的潜在关联。选择FVC作为肺功能的主要指标,因为它对努力和认知的依赖性较小,能更好地反映整体肺活量。结果包括6种痴呆类型:全因痴呆、阿尔茨海默病(AD)、路易体痴呆、帕金森病痴呆、额颞叶痴呆和血管性痴呆,以及6个认知领域,包括智力、流体智力(独立于获得知识的推理和解决问题的能力)、认知表现、数字记忆、执行功能和前瞻性记忆。基因预测FVC每增加1个标准差就报告了所有的遗传关联——痴呆结局用对数比值比(log- or)表示,认知结局用标准偏差变化表示。以反方差加权法为主要分析方法,辅以MR-Egger、加权中位数、加权模式、简单模式和MR-PRESSO进行敏感性分析。错误发现率(FDR)校正、共定位和反向MR分析也被执行。这项研究提供了支持肺功能下降和认知障碍之间关联的遗传证据。需要进一步的研究来阐明潜在的机制。较高的遗传预测FVC与较低的AD风险相关(每1-SD增加log-OR = -0.24; P = 0.002; fdr校正P = 0.011)。还观察到与全因痴呆呈负相关(每1-SD增加log-OR = -0.37; P =。031),但在FDR校正后(FDR校正P = 0.094),该差异不显著。其他痴呆亚型或认知结果未观察到显著关联。结果在敏感性分析中是稳健的,在反向mr中没有显著的发现,共定位分析不支持FVC和AD之间共有的因果变异(PP.H4.abf)
{"title":"Genetic evidence on the association between pulmonary function and cognitive impairment: A 2-sample Mendelian randomization study.","authors":"Xinran Cui, Weijie Zhai, Zixun Wang, Yanjiao Xu, Dongyao Fan, Qi Zhang, Li Sun","doi":"10.1097/MD.0000000000047457","DOIUrl":"10.1097/MD.0000000000047457","url":null,"abstract":"<p><p>Some observational studies have suggested that lower pulmonary function increases the risk of cognitive decline or dementia; however, the evidence remains inconclusive. We performed 2-sample Mendelian randomization (MR) analyses to investigate the potential associations between forced vital capacity (FVC) and a range of dementia- and cognition-related outcomes. FVC was selected as the primary indicator of pulmonary function because it is less effort- and cognition-dependent and better reflects overall lung capacity. Outcomes included 6 dementia types: all-cause dementia, Alzheimer disease (AD), dementia with lewy bodies, Parkinson disease dementia, frontotemporal dementia, and vascular dementia, and 6 cognitive domains, including intelligence, fluid intelligence (reasoning and problem-solving ability independent of acquired knowledge), cognitive performance, numeric memory, executive function, and prospective memory. All genetic associations were reported per 1-standard-deviation increase in genetically predicted FVC - expressed as log-odds ratios (log-ORs) for dementia outcomes and standard-deviation changes for cognitive outcomes. The inverse-variance weighted method was used as the primary analysis, complemented by MR-Egger, weighted median, weighted mode, simple mode and MR-PRESSO for sensitivity analyses. False discovery rate (FDR) correction, colocalization, and reverse MR analyses were also performed. This study provides genetic evidence supporting an association between reduced pulmonary function and cognitive impairment. Further studies are needed to clarify the underlying mechanisms. Higher genetically predicted FVC was associated with a lower risk of AD (log-OR per 1-SD increase = -0.24; P = .002; FDR-adjusted P = .011). An inverse association was also observed with all-cause dementia (log-OR per 1-SD increase = -0.37; P = .031), but it did not remain significant after FDR correction (FDR-adjusted P = .094). No significant associations were observed for other dementia subtypes or cognitive outcomes. The results were robust in sensitivity analyses, with no significant findings in reverse MR. Colocalization analysis did not support shared causal variants between FVC and AD (PP.H4.abf <0.75).</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 6","pages":"e47457"},"PeriodicalIF":1.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1097/MD.0000000000047614
Xinxin Xu, Hongyu Ye, Qingwei Ren, Xuejun Shao, Jianlong Wang, Ying Shi, Yueting Du
Gut microbiota dysbiosis is increasingly recognized as a contributor to inflammatory bowel disease (IBD), yet causal relationships and underlying mechanisms remain unclear. Ferroptosis, an iron-dependent form of regulated cell death, plays a key role in epithelial barrier damage and inflammation. This study aimed to determine whether specific gut microbial taxa are causally associated with IBD and whether ferroptosis-related genes mediate this association using Mendelian randomization (MR). Two-sample MR and mediation MR analyses were performed using genome-wide association study summary data from the FinnGen consortium (IBD), the genome-wide association study catalog (473 gut microbial taxa), and the deCODE database (ferroptosis-related genes). Instrumental variables were selected with thresholds of P < 1 × 10-6 for microbes and P < 5 × 10-8 for traits, and linkage disequilibrium clumping (r2 < 0.001) was applied. Twenty-three microbial taxa showed significant causal associations with IBD (e.g., Chromatiales, OR = 0.51; Acetobacterales, OR = 2.61). Several ferroptosis-related genes were linked to IBD risk (e.g., GPX4, STAT3, IDO1). Mediation MR revealed that genes such as MUC1, IDO1, and ADAM23 partially mediated microbial effects on IBD, with mediation proportions up to 7.6%. This study provides novel genetic evidence supporting a gut microbiota-ferroptosis-IBD axis. Ferroptosis-related pathways may partially mediate microbial effects on IBD pathogenesis and represent promising targets for future therapeutic interventions.
{"title":"Ferroptosis as a mediator of gut microbiota-driven inflammatory bowel disease: Evidence from genetic analyses.","authors":"Xinxin Xu, Hongyu Ye, Qingwei Ren, Xuejun Shao, Jianlong Wang, Ying Shi, Yueting Du","doi":"10.1097/MD.0000000000047614","DOIUrl":"10.1097/MD.0000000000047614","url":null,"abstract":"<p><p>Gut microbiota dysbiosis is increasingly recognized as a contributor to inflammatory bowel disease (IBD), yet causal relationships and underlying mechanisms remain unclear. Ferroptosis, an iron-dependent form of regulated cell death, plays a key role in epithelial barrier damage and inflammation. This study aimed to determine whether specific gut microbial taxa are causally associated with IBD and whether ferroptosis-related genes mediate this association using Mendelian randomization (MR). Two-sample MR and mediation MR analyses were performed using genome-wide association study summary data from the FinnGen consortium (IBD), the genome-wide association study catalog (473 gut microbial taxa), and the deCODE database (ferroptosis-related genes). Instrumental variables were selected with thresholds of P < 1 × 10-6 for microbes and P < 5 × 10-8 for traits, and linkage disequilibrium clumping (r2 < 0.001) was applied. Twenty-three microbial taxa showed significant causal associations with IBD (e.g., Chromatiales, OR = 0.51; Acetobacterales, OR = 2.61). Several ferroptosis-related genes were linked to IBD risk (e.g., GPX4, STAT3, IDO1). Mediation MR revealed that genes such as MUC1, IDO1, and ADAM23 partially mediated microbial effects on IBD, with mediation proportions up to 7.6%. This study provides novel genetic evidence supporting a gut microbiota-ferroptosis-IBD axis. Ferroptosis-related pathways may partially mediate microbial effects on IBD pathogenesis and represent promising targets for future therapeutic interventions.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"105 6","pages":"e47614"},"PeriodicalIF":1.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}