ObjectiveTo investigate the therapeutic effect of Siegesbeckiae Herba water decoction （SWD） at different doses on atherosclerosis （AS） in a mouse model induced by a high-fat diet and analyze its potential mechanism of action. MethodsThirty-six male ApoE^-/- mice were randomly divided into six groups： blank control group， model group， low-dose， medium-dose， and high-dose SWD groups， and positive control group. Firstly， the AS mouse model was created by feeding mice a high-fat diet. After successful modeling， the low-， medium-， and high-dose SWD groups were intragastrically administered with SWD at 0.65， 1.3， 2.6 g·kg^-1， respectively. The positive control group was intragastrically administered with 30 mg·kg^-1 of atorvastatin calcium aqueous solution， while the blank and model groups received an equal volume of 0.9% sodium chloride solution via oral gavage， all administered for 12 weeks. During the administration period， the general condition of the mice was observed and recorded daily. Before sampling， color Doppler ultrasound was performed to observe the pathological changes in atherosclerotic plaques in the aortic wall of mice. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in aortic tissue in mice， and oil red O staining was used to detect the atherosclerotic plaque area in the aorta. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum lipid indices and the levels of interleukins （IL-1β， IL-4， IL-6， and IL-10） and tumor necrosis factor-α （TNF-α） in mice. Protein expression levels of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue were detected by Western blot. ResultsCompared with the blank control group， the model group showed a significant increase in body weight. The results of color Doppler ultrasound showed enhanced vascular wall echo， suggesting the presence of atherosclerotic plaques. HE staining showed foam cell aggregation， fibrous connective tissue proliferation， and vascular intima injury in the aortic tissue. Oil red O staining showed a significant increase in the plaque area in the aortic tissue （P<0.01）. ELISA results indicated significantly elevated levels of IL-1β， IL-6， TNF-α， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein （LDL） in mouse serum （P<0.01）， as well as significantly decreased levels of IL-4， IL-10， and high-density lipoprotein （HDL） （P<0.01）. Western blot results showed that the expression of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue increased significantly （P<0.01）. Compared with those in the model group， mice in the middle- and high-dose SWD groups showed significant weight loss. In the high-dose group， the aortic vascular wall echoes were weakened， and the atherosclerotic plaques were reduced. The aortic lesions of mice in the medium- and high-dose SWD groups were significantly alleviated. The plaque area percentage showed an inverse correlation with the administered dose in all groups treated with SWD （P<0.05）. In the medium-dose SWD group， serum levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）， while those of IL-4 and IL-10 were significantly increased （P<0.01）. In the high-dose SWD group， levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.01）， while IL-4， IL-10， and HDL were significantly increased （P<0.01）. The IKKα and IKKβ expression was significantly decreased in the low-dose SWD group （P<0.05）， and IKKα， IKKβ， and NF-κB p65 were significantly decreased in the medium- and high-dose SWD groups （P<0.05， P<0.01）. ConclusionSWD may exert therapeutic effects on AS by regulating the expression of related inflammatory factors through the NF-κB signaling pathway， thereby reducing inflammation， plaque area， and lipid content in the body.

The pathogenesis of neurodegenerative diseases (NDDs) is fundamentally linked to complex and profound alterations in metabolic networks within the brain, which exhibit marked spatial heterogeneity. While conventional bulk metabolomics is powerful for detecting global metabolic shifts, it inherently lacks spatial resolution. This methodological limitation hampers the ability to interrogate critical metabolic dysregulation within discrete anatomical brain regions and specific cellular microenvironments, thereby constraining a deeper understanding of the core pathological mechanisms that initiate and drive NDDs. To address this critical gap, spatial metabolomics, with mass spectrometry imaging (MSI) at its core, has emerged as a transformative approach. It uniquely overcomes the limitations of bulk methods by enabling high-resolution, simultaneous detection and precise localization of hundreds to thousands of endogenous molecules—including primary metabolites, complex lipids, neurotransmitters, neuropeptides, and essential metal ions—directly in situ from tissue sections. This powerful capability offers an unprecedented spatial perspective for investigating the intricate and heterogeneous chemical landscape of NDD pathology, opening new avenues for discovery. Accordingly, this review provides a comprehensive overview of the field, beginning with a discussion of the technical features, optimal application scenarios, and current limitations of major MSI platforms. These include the widely adopted matrix-assisted laser desorption/ionization (MALDI)-MSI, the ultra-high-resolution technique of secondary ion mass spectrometry (SIMS)-MSI, and the ambient ionization method of desorption electrospray ionization (DESI)-MSI, along with other emerging technologies. We then highlight the pivotal applications of spatial metabolomics in NDD research, particularly its role in elucidating the profound chemical heterogeneity within distinct pathological microenvironments. These applications include mapping unique molecular signatures around amyloid β‑protein (Aβ) plaques, uncovering the metabolic consequences of neurofibrillary tangles composed of hyperphosphorylated tau protein, and characterizing the lipid and metabolite composition of Lewy bodies. Moreover, we examine how spatial metabolomics contributes to constructing detailed metabolic vulnerability maps across the brain, shedding light on the biochemical factors that render certain neuronal populations and anatomical regions selectively susceptible to degeneration while others remain resilient. Looking beyond current applications, we explore the immense potential of integrating spatial metabolomics with other advanced research methodologies. This includes its combination with three-dimensional brain organoid models to recapitulate disease-relevant metabolic processes, its linkage with multi-organ axis studies to investigate how systemic metabolic health influences neurodegeneration, and its convergence with single-cell and subcellular analyses to achieve unprecedented molecular resolution. In conclusion, this review not only summarizes the current state and critical role of spatial metabolomics in NDD research but also offers a forward-looking perspective on its transformative potential. We envision its continued impact in advancing our fundamental understanding of NDDs and accelerating translation into clinical practice—from the discovery of novel biomarkers for early diagnosis to the development of high-throughput drug screening platforms and the realization of precision medicine for individuals affected by these devastating disorders.

On August 2-4,2023,the"Third Summit Forum on'Building a Community of Shared Future for Doctors and Patients'"was jointly organized by institutions such as the Chinese Medical Ethics,the Hospital Humanities Management and Talent Training Special Committee of the China Population and Culture Promotion Association,Center for Ethical Studies of Renmin University of China,the Newspaper for China's Physicians,the China Health Law Society,the China Anti-Cancer Association,and the China Association For Ethical Studies in Harbin.The conference arranged a sub-forum for the"Seminar on the Construction of Chinese Medical Humanities",with domestic medical humanities scholars attending the conference.After heated discussions at the seminar,the Scholars'Consensus on the Construction and Development of Chinese Medical Humanities was formed.It was proposed that in the new era,it is urgent to build the medical humanities discipline,as well as lead the academic integration and development of medical humanities under the core socialist values.At the same time,for the construction of the medical humanities discipline,it is necessary to optimize the organizational mechanism,prosper and develop the overall framework of the medical humanities discipline,accelerate the construction of a professional teaching team for the medical humanities discipline,promote the establishment of a new carrier medical humanities education and teaching in cultivating morality and nurturing talents,as well as focus on solving problems related to the cultivation of medical humanities graduate students.

Smoking is the leading preventable risk factor for disease and death worldwide. Tobacco and its smoke contain a complex mix of over 9 500 chemical substances, including oxidative gases, heavy metals, and 83 known carcinogens. Long-term smoking is a significant risk factor for respiratory diseases such as acute lung injury, emphysema, and pulmonary fibrosis. Damage to alveolar epithelial cells (AECs) is a common pathological feature in these smoking-related lung diseases. AECs, which line the surface of the alveoli, play a crucial role in preventing overexpansion or collapse, secreting cell factors and surfactants, containing abundant mitochondria, and being essential for lung tissue maturation, gas exchange, metabolism, and repair after damage. Damage to these cells can lead to pulmonary edema and alveolar collapse. Cigarette smoke (CS) can disrupt alveolar epithelial cell function through various pathways, resulting in cell death, tissue damage, and the development of lung diseases.This review summarizes recent research on the damage caused by CS to AECs, showing that CS can promote cell death and damage through induction of oxidative stress, autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, inflammation, and epithelial-mesenchymal transition. It also affects the proliferative function of alveolar type II epithelial cells. The review highlights that CS-induced oxidative stress is a key factor in causing various types of damage, with TRP ion channels serving as important triggers. Inhibiting CS-induced oxidative damage can significantly prevent cell death and subsequent diseases such as pulmonary emphysema. The activation of the same pathway induced by CS can lead to different types of cell damage, potentially encouraging the development of different diseases. CS can either directly induce or indirectly promote cell inflammation through endoplasmic reticulum stress, mitochondrial dysfunction, and senescence. There are interconnected relationships between these mechanisms, and SIRT1 is an important protein in preventing CS-induced AECs damage. Increasing SIRT1 activity can alleviate CS-induced autophagy, endoplasmic reticulum stress, and senescence in various cell damages; its substrate NAD⁺ is already used clinically, and its effectiveness in COPD treatment deserves further exploration. The impact of CS on cells varies based on concentration: lower concentrations stimulate stress responses or apoptosis, while higher concentrations lead to apoptosis or necrosis through various mechanisms, ultimately impairing lung epithelial function. When external stimuli exceed the cells’ self-healing capacity, they can cause damage to cells, lung epithelial barriers, and alveoli, promoting the development of related lung diseases. Key proteins that play a protective role may serve as potential targets to mitigate cell damage.This review provides insights into the various mechanisms through which CS induces damage to AECs, covering important transcription factors, DNA repair proteins, and membrane channel proteins, paving the way for the study of new mechanisms and pathways. However, there are still unanswered questions, such as the need for further exploration of the upstream pathways of CS-induced autophagy in AECs and the intrinsic mechanisms of CS in enhancing the stem cell properties of AECs and its relationship to the occurrence of lung cancer.It is expected that this article will provide a theoretical basis for future research on the mechanisms of lung epithelial cell damage caused by CS or its individual components and inspire clinical strategies for the prevention and treatment of smoking-related lung diseases.

The International Consortium for Health Outcomes Measurement has released the first international standard set of outcome measures for patients with venous thromboembolism, providing a widely applicable and easy-to-use standardized set of outcome measures for venous thromboembolism, including disease-specific complications, treatment-related comorbidities, long term consequences of the disease, and patient-reported outcomes. This paper combines clinical practice in China to interpret the Core Outcome Set for Venous Thromboembolism, in order to provide reference for the selection of outcomes of venous thromboembolism and promote the application of the core outcome set of venous thromboembolism in clinical practice and research in China.

OBJECTIVE: This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn's disease (CD) regulated by moxibustion through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR). METHODS: Sprague-Dawley rats were randomly divided into control group, CD model group, mild moxibustion group and herb-partitioned moxibustion group. CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6). The changes in CD symptoms were rated according to the disease activity index score, the serum and colon tissues of rats were collected, and the pathological changes in colon tissues were observed via histopathology. Western blot, immunohistochemistry (IHC) and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FXR pathway. RESULTS: Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD, inhibited inflammation and repaired mucosal damage to the colon in CD rats. Meanwhile, moxibustion could improve the abnormal expression of BA in the colon, liver and serum, downregulate the expression of interferon-γ and upregulate the expression of FXR mRNA, and inhibit Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA. The IHC results showed that moxibustion could upregulate the expression of FXR and mucin2 and inhibit TLR4 expression. Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FXR. Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FXR with TLR4 or nuclear factor-κB p65. In particular, herb-partitioned moxibustion has more advantages in improving BA and upregulating FXR and TLR4 in the colon. CONCLUSION Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA, activating colonic FXR, regulating the TLR4/MyD88 pathway, inhibiting intestinal inflammation and repairing the intestinal mucosal barrier. Herb-partitioned moxibustion seems to have more advantages in regulating BA enterohepatic circulation and FXR activation. Please cite this article as: Shen JC, Qi Q, Han D, Lu Y, Huang R, Zhu Y, Zhang LS, Qin XD, Zhang F, Wu HG, Liu HR. Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid X receptor. J Integr Med. 2023; 21(2): 194-204.
Rats ; Animals ; Crohn Disease/pathology* ; Moxibustion/methods* ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Myeloid Differentiation Factor 88/metabolism* ; Colitis ; Inflammation ; Enterohepatic Circulation ; RNA, Messenger/metabolism*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective:To explore the impacts of comprehensive geriatric assessment (CGA) on setup errors during the radiotherapy of elderly patients with rectal cancer.Methods:A total of 45 patients over 70 years of age and receiving radiotherapy were enrolled in the study. A comprehensive geriatric assessment was conducted before the radiotherapy. The enrolled patients had a median age of 77 years, including 28 male and 17 female cases. Meanwhile, 31 patients were determined to be in a good CGA status and 14 were determined to be in a poor CGA status, and 35 patients received radiotherapy in the prone position and 10 in the supine position. Cone beam CT (CBCT) was used for setup correction during radiotherapy. CBCT was performed daily in the first week and once a week from the second week. By fusing and aligning the CBCT images with simulation CT images according to the lumbar vertebra, setup errors in the left-right ( x axis), cranio-caudal ( y axis), and anterior-posterior ( z axis) directions were obtained. A total of 338 CBCT images were obtained. A generalized linear model was used to evaluate the effects of multiple factors on the setup errors. Results:During the radiotherapy, setup errors of all patients were (0.24±0.19) cm in the left-right direction, (0.33±0.25) cm in the cranio-caudal direction, and (0.19±0.15) cm in the anterior-posterior direction. The setup error in the cranio-caudal direction was more than that in the left-right direction and that in the anterior-posterior direction ( Z=-4.86, -7.72, P< 0.001). The setup error in the left-right direction was greater than that in the anterior-posterior direction ( Z=-2.79, P=0.005). The mean setup errors of the good and poor status groups in the left-right direction were (0.21 ± 0.17) and (0.30 ± 0.22) cm, respectively ( Z=2.16, P=0.031). There was no statistically significant difference in the setup errors between cranio-caudal direction and anterior-posterior direction ( P>0.05). The setup errors in the anterior-posterior direction were (0.17 ± 0.13) and (0.27 ± 0.19) cm, respectively for the prone and supine positions during the radiotherapy ( Z=2.85, P=0.004). There was no statistically significant difference in the setup errors between the left-right direction and the cranio-caudal direction ( P>0.05). Conclusion:The status of CGA elderly patients with rectal cancer affects the setup error in the left-right direction. It may be necessary to clinically adjust the PTV margin.

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Animals ; China ; Genomics ; Humans ; Male ; Pesticides ; Spodoptera/genetics* ; Transcriptome

Objective: To explore the relationship between DNA methylation and occupational noise-induced hearing loss. Methods: A case-control study was conducted. People with hearing loss induced by occupational noise were recruited as the case group and those with normal hearing but still exposed to occupational noise were recruited as the control group. A total of 60 participants were included, of which 30 participants were in the case group and 30 in the control group. The methylation level was detected by 850k genome-wide DNA methylation chip technology. The significance of differential methylated position (DMP) was tested by R-packet 'Champ'. The differential methylated region (DMR) was analyzed by using Champ's Bumphunter algorithm. Cluster profiler was used to analyze the gene list for GO and KEGG pathway enrichment. Results: There was significant difference between two groups in binaural high-frequency average hearing threshold (P<0.05), but there was no significant difference in age, smoking, drinking, hypertension, physical exercise and cumulative noise exposure. The results of DMP and DMR analysis showed that 713875 sites were detected in the case group and the control group, and 439 methylation sites with significant difference, accounting for 0.06%; 650 regions were detected, and 72 methylation regions with significant differences, accounting for 11.08%. Compared with the control group, the results of GO enrichment analysis showed that the case group had statistically significant differences in four pathways: axogenesis of projection neurons in the central nervous system, neuronal development in the central nervous system, axogenesis of neurons in the central nervous system and neuronal differentiation in the central nervous system. KEGG enrichment analysis showed that there were significant differences in sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis pathway between the case group and the control group. Conclusion: The occurrence of occupational noise-induced hearing loss may be related to the regulation of gene expression related to axogenesis of projection neurons in the central nervous system, development of neurons in the central nervous system, axogenesis of neurons in the central nervous system, differentiation of neurons in the central nervous system, sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis and gene methylation related to metabolism.
Aldosterone ; Bile Acids and Salts ; Case-Control Studies ; DNA Methylation ; Hearing Loss, Noise-Induced/genetics* ; Humans ; Noise, Occupational/adverse effects* ; Occupational Diseases ; Occupational Exposure ; Sphingolipids