Search

Abstract Mass spectrometry imaging (MSI)‐based spatially resolved metabolomics addresses the limitations inherent in traditional liquid chromatography‐tandem mass spectrometry (LC–MS)‐based metabolomics, particularly the loss of spatial context within heterogeneous tissues. MSI not only enhances our understanding of disease aetiology but also aids in the identification of biomarkers and the assessment of drug toxicity and therapeutic efficacy by converting invisible metabolites and biological networks into visually rendered image data. In this comprehensive review, we illuminate the key advancements in MSI‐driven spatially resolved metabolomics over the past few years. We first outline recent innovations in preprocessing methodologies and MSI instrumentation that improve the sensitivity and comprehensiveness of metabolite detection. We then delve into the progress made in functional visualization techniques, which enhance the precision of metabolite identification and annotation. Ultimately, we discuss the significant potential applications of spatially resolved metabolomics technology in translational medicine and drug development, offering new perspectives for future research and clinical translation. Highlights MSI‐driven spatial metabolomics preserves metabolite spatial information, enhancing disease analysis and biomarker discovery. Advances in MSI technology improve detection sensitivity and accuracy, expanding bioanalytical applications. Enhanced visualization techniques refine metabolite identification and spatial distribution analysis. Integration of MSI with AI promises to advance precision medicine and accelerate drug development.

Abstract Background Paranasal sinus angiosarcoma is an uncommon malignancy, with only a few reported cases worldwide. Although it exhibits multiple symptoms, facial paralysis has not been previously documented as a noticeable presentation. Case Presentation In this case, we report a 40-year-old male who presented with facial numbness and pain for one month, weakness of his facial muscles for 15 days, and recurrent right epistaxis for 1 year. He had a history of nasal inflammatory polyps with chronic sinusitis. Computed tomography and magnetic resonance imaging showed space-occupying lesions in the right nasal cavity and maxillary sinus, with bone destruction occurring in the sinus wall and turbinate. This patient then underwent endoscopic surgery. According to the histopathological and immunohistochemical results, he was eventually diagnosed with paranasal sinus angiosarcoma in April 2021. To date, this patient has not initiated any radiotherapy or chemotherapy and has survived with lymphatic metastasis for at least 3 years. Conclusions This manuscript suggests that paranasal sinus angiosarcoma can present with facial paralysis. Moreover, pathological and immunohistochemical tests are still vital for diagnosing paranasal sinus angiosarcoma and differential diagnosis. Additionally, regular follow-up is crucial for patients with paranasal sinus angiosarcoma, enabling monitoring of recurrence, metastasis, and recovery while contributing valuable clinical data to understanding this rare disease and associated research endeavours.

Tumors are spatially heterogeneous tissues that comprise numerous cell types with intricate structures. By interacting with the microenvironment, tumor cells undergo dynamic changes in gene expression and metabolism, resulting in spatiotemporal variations in their capacity for proliferation and metastasis. In recent years, the rapid development of histological techniques has enabled efficient and high-throughput biomolecule analysis. By preserving location information while obtaining a large number of gene and molecular data, spatially resolved metabolomics (SRM) and spatially resolved transcriptomics (SRT) approaches can offer new ideas and reliable tools for the in-depth study of tumors. This review provides a comprehensive introduction and summary of the fundamental principles and research methods used for SRM and SRT techniques, as well as a review of their applications in cancer-related fields.

Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy. However, metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity. Herein, choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types, and a choline-modified strategy for small molecule-drug conjugates (SMDCs) design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy, instead of directly inhibiting choline metabolism. As a proof-of-concept, choline-modified SMDCs were designed, screened, and investigated for their druggability in vitro and in vivo. This strategy improved tumor targeting, preserved tumor inhibition and reduced toxicity of paclitaxel, through targeted drug delivery to tumor by highly expressed choline transporters, and site-specific release by carboxylesterase. This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.

Abstract Mapping tumor metabolic remodeling and their spatial crosstalk with surrounding non-tumor cells can fundamentally improve our understanding of tumor biology, facilitates the designing of advanced therapeutic strategies. Here, we present an integration of mass spectrometry imaging-based spatial metabolomics and lipidomics with microarray-based spatial transcriptomics to hierarchically visualize the intratumor metabolic heterogeneity and cell metabolic interactions in same gastric cancer sample. Tumor-associated metabolic reprogramming is imaged at metabolic-transcriptional levels, and maker metabolites, lipids, genes are connected in metabolic pathways and colocalized in the heterogeneous cancer tissues. Integrated data from spatial multi-omics approaches coherently identify cell types and distributions within the complex tumor microenvironment, and an immune cell-dominated “tumor-normal interface” region where tumor cells contact adjacent tissues are characterized with distinct transcriptional signatures and significant immunometabolic alterations. Our approach for mapping tissue molecular architecture provides highly integrated picture of intratumor heterogeneity, and transform the understanding of cancer metabolism at systemic level.

This study investigated the effect of Bacillus licheniformis VLPPro® SB538 supplementation on hybrid grouper's culture water quality, growth performance, and intestinal health. A total of 240 juvenile hybrid grouper were randomly distributed into four experimental groups (n = 20, 718.15 ± 16.12 g): 0 g/m³ (the control group, WT), 0.375 g/m³ (the low concentration group, WL), 0.750 g/m³ (the moderate concentration group, WM), and 1.500 g/m³ (the high concentration group, WH). The experiment was conducted in triplicate tanks for 4 weeks. Water quality parameters, including ammonia, nitrite, nitrate, and phosphate, were monitored regularly. Growth performance parameters such as weight gain, specific growth rate, and feed conversion ratio were recorded. Additionally, the intestinal health of the fish was assessed by examining the histopathological changes and the expression of intestinal permeability-related substances in the gut. The results revealed that Bacillus licheniformis supplementation significantly improved the water quality in the culture tanks, as evidenced by reduced ammonia and nitrite levels. Furthermore, hybrid grouper in the treatment group exhibited significantly enhanced growth performance, including higher weight gain and specific growth rate, along with a reduced feed conversion ratio compared to the control group. Intestinal health was also positively influenced by Bacillus licheniformis, as indicated by histopathological analysis. Moreover, the decreased concentration of D-lactic and the amelioration of hindgut morphology indicated that Bacillus licheniformis possessed the function of improving intestinal health in hybrid grouper. The findings of this study demonstrate the beneficial effects of Bacillus licheniformis supplementation on the culture water quality, growth performance, and intestinal health of hybrid grouper. The improved water quality and enhanced growth performance can contribute to grouper aquaculture's sustainability and economic viability.

The brain is the most advanced organ with various complex structural and functional microregions. It is often challenging to understand what and where the molecular events would occur for a given drug treatment in the brain. Herein, a temporo-spatial pharmacometabolomics method was proposed based on ambient mass spectrometry imaging and was applied to evaluate the microregional effect of olanzapine (OLZ) on brain tissue and demonstrate its effectiveness in characterizing the microregional pharmacokinetics and pharmacodynamics of OLZ for improved understanding of the molecular mechanism of drugs acting on the microregions of the brain. It accurately and simultaneously illustrated the levels dynamics and microregional distribution of various substances, including exogenous drugs and its metabolites, as well as endogenous functional metabolites from complicated brain tissue. The targeted imaging analysis of the prototype drug and its metabolites presented the absorption, distribution, metabolism, and excretion characteristics of the drug itself. Moreover, the endogenous functional metabolites were identified along with the associated therapeutic and adverse effects of the drug, which can reflect the pharmacodynamics effect on the microregional brain. Therefore, this method is significant in elucidating and understanding the molecular mechanism of central nervous system drugs at the temporo and spatial metabolic level of system biology.

The individual Probiotic application has become increasingly widespread in aquaculture and has been extensively studied. However, investigating probiotics as water additives in the grouper culture is still lacking. This study evaluated the functional efficacy of the Bacillus subtilis CICC 10071 (3 × 1011 CFU / g) and Lactobacillus sp. (8 × 1011 CFU / g) combination in a 1:1 ratio on the rearing water quality, water microbial community structure, and growth performance of hybrid grouper. Depending on the additive concentrations of probiotics, we designed four groups, each in triplicate: control (WT, 0g/m3), low concentration (WL, 0.038g/m3), middle concentration (WM, 0.075g/m3), and high concentration (WH, 0.113g/m3). The result shows that throughout the 22-day feeding period, the water supplementation of probiotics significantly decreased Ammonia (NH3) and nitrite (NO2-) in culture water. Final weight (FW), Specific growth rate (SGR), and Weight gain rate (WGR) in treated groups were higher than that in the control group (P

Abstract Background Depression and chronic musculoskeletal pain (CMSP) are the leading causes of years lived with disabling diseases worldwide. Moreover, they often commonly coexist, which makes diagnosis and treatment difficult. A safe and effective treatment is urgently needed. Previous studies have shown that acupuncture is a cost-effective treatment for simple depression or CMSP. However, there is limited evidence that acupuncture is effective for depression comorbid with CMSP. Methods This is a randomized, sham acupuncture-controlled trial with three arms: real acupuncture (RA), sham acupuncture (SA), and healthy control (HC). Forty-eight depression combined CMSP participants and 12 healthy people will be recruited from GDTCM hospital and randomized 2:2:1 to the RA, SA, and HC groups. The patients will receive RA or SA intervention for 8 weeks, and HC will not receive any intervention. Upon completion of the intervention, there will be a 4-week follow-up. The primary outcome measures will be the severity of depression and pain, which will be assessed by the Hamilton Depression Rating Scale (HAMD-17) and Brief Pain Inventory (BPI), respectively. The secondary outcome measures will be cognitive function and quality of life, which will be measured by the Montreal Cognitive Assessment (MoCA), P300, and World Health Organization Quality of Life (WHOQOL-BREF). In addition, the correlation between brain-derived neurotrophic factor (BDNF) and symptoms will also be determined. Discussion The aim of this study is to evaluate the clinical efficacy and underlying mechanism of acupuncture in depression comorbid with CMSP. This study could provide evidence for a convenient and cost-effective means of future prevention and treatment of combined depression and CMSP. Trial registration Chinese Clinical Trial Registry ChiCTR1800014754 . Preregistered on 2 February 2018. The study is currently recruiting.

We aimed to investigate the effects of dietary alpha-lipoic acid (α-LA) on the growth performance, serum biochemical indexes, liver morphology, antioxidant capacity, and transcriptome of juvenile hybrid groupers (Epinephelus fuscoguttatus♀ × Epinephelus polyphekadion♂). Four experimental diets supplemented with 0 (SL0), 0.4 (L1), 0.6 (L2), and 1.2 (L3) g/kg α-LA were formulated and fed to three replicates of juvenile hybrid grouper (24.06 ± 0.15 g) for 56 d. The results indicated that dietary 0.4 and 0.6 g/kg α-LA significantly decreased the weight gain rate in juvenile hybrid groupers. Compared with SL0, the content of total protein in the serum of L1, L2, and L3 increased significantly, and alanine aminotransferase decreased significantly. The content of albumin in the serum of L3 increased significantly, and triglyceride, total cholesterol, and aspartate aminotransferase decreased significantly. In addition, the hepatocyte morphology in L1, L2, and L3 all showed varying degrees of improvement, and the activities of glutathione peroxidase and superoxide dismutase in the liver of L2 and L3 were significantly increased. A total of 42 differentially expressed genes were screened in the transcriptome data. KEGG showed that a total of 12 pathways were significantly enriched, including the pathway related to immune function and glucose homeostasis. The expression of genes (ifnk, prl4a1, prl3b1, and ctsl) related to immune were significantly up-regulated, and the expressions of gapdh and eno1 genes related to glucose homeostasis were significantly down-regulated and up-regulated, respectively. In summary, dietary supplementation of 0.4 and 0.6 g/kg α-LA inhibited the growth performance of juvenile hybrid groupers. A total of 1.2 g/kg α-LA could reduce the blood lipid level, improve hepatocyte damage, and increase the hepatic antioxidant enzyme activity. Dietary α-LA significantly affected the pathway related to immune function and glucose homeostasis.

Abstract Background Numerous randomized controlled trials on the effects of electro-acupuncture have been conducted to treat dysphagia as a sequela of stroke. However, the normal physiological mechanisms of swallowing and the pathological mechanisms of dysphagia are not fully understood. The purpose of this study is to investigate whether lateralization of the human swallowing motor cortex excitability in healthy subjects will be influenced by electro-acupuncture to Lianquan (CV 23) and Fengfu (GV 16), which may provide insight into the pathological mechanisms of dysphagia after stroke. Methods We designed a single-blind, randomized, sham-controlled trial in which 40 healthy subjects will be recruited. Subjects will be randomized 1:1 into two groups: the electro-acupuncture group and the sham-control electro-acupuncture group. The swallowing motor cortex will be located in both groups using a neuroimaging navigation system. Then left and right cortical stimulation will be measured by transcranial magnetic stimulation (TMS) before and after electro-acupuncture or sham electro-acupuncture. The electro-acupuncture or sham electro-acupuncture interventions will last for 15 min. The primary outcome measure will be percent change in the resting motor threshold (RMT) of the mylohyoid. The secondary outcome measures will be the amplitude (μV) and latency (ms) of the motor evoked potential (MEP) of the mylohyoid as a proxy for the TMS evoked potential. All outcomes will be measured at baseline and after the electro-acupuncture or sham electro-acupuncture treatment. Discussion The aim of this trial is to explore whether lateralization of the human swallowing motor cortex excitability in healthy subjects is present, and to determine if electro-acupuncture to acupuncture points Lianquan (CV 23) and Fengfu (GV 16) will exert an effect on it under normal physiological conditions. Trial registration Chinese Clinical Trial Registry, ChiCTR-IOR-17011359. Registered on 11 May 2017.

Somatosensory stimulation can effectively induce plasticity in the motor cortex representation of the stimulated body part. Specific interactions have been reported between different representations within the primary motor cortex. However, studies evaluating somatosensory stimulation-induced plasticity between different representations within the primary motor cortex are sparse. The purpose of this study was to investigate the effect of somatosensory stimulation on the modulation of plasticity between different representations within the primary motor cortex. Twelve healthy volunteers received both electroacupuncture (EA) and sham EA at the TE5 acupoint (located on the forearm). Plasticity changes in different representations, including the map volume, map area, and centre of gravity (COG) were evaluated by transcranial magnetic stimulation (TMS) before and after the intervention. EA significantly increased the map volume of the forearm and hand representations compared to those of sham EA and significantly reduced the map volume of the face representation compared to that before EA. No significant change was found in the map volume of the upper arm and leg representations after EA, and likewise, no significant changes in map area and COG were observed. These results suggest that EA functions as a form of somatosensory stimulation to effectively induce plasticity between different representations within the primary motor cortex, which may be related to the extensive horizontal intrinsic connectivity between different representations. The cortical plasticity induced by somatosensory stimulation might be purposefully used to modulate human cortical function.

Abstract Background Acupuncture has been widely applied in the clinic to treat irritable bowel syndrome (IBS), but the underlying mechanism remains unknown. Diffuse noxious inhibitory control (DNIC) is deficient in patients with IBS, which attenuates the systemic analgesic effect elicited by noxious stimulation that is remote from pain areas. Therefore, the aim of this study is to investigate the analgesic effect of electroacupuncture (EA) at homotopic or heterotopic acupoints on abdominal pain in patients with IBS. Methods/design This study is a randomized, single-blinded, controlled, four-arm parallel trial. A total of 144 patients will be randomly assigned to four groups: a homotopic noxious stimulation group (group A), a homotopic innocuous stimulation group (group B), a heterotopic noxious stimulation group (group C), and a heterotopic innocuous stimulation group (group D). Each patient will receive 14 sessions of treatment, twice per week for 7 weeks. The primary outcome will be pain intensity measured with the visual analog scale. The secondary outcomes will include the IBS Symptom Severity Scale, IBS Quality of Life questionnaire, pain threshold (PT), and the Symptom Checklist-90 for psychological distress. The PT will be measured before and after every treatment. All other outcomes will be evaluated before the 1st treatment, after 7th and 14th treatment, and 3 months later during follow-up. Discussion The aim of this study is to assess the analgesic effect of EA at homotopic (abdomen) acupoints and heterotopic (lower limb) acupoints on abdominal pain in patients with IBS, as well as the difference in analgesic effects between noxious and innocuous stimulation. Trial registration Chinese Clinical Trial Registry, ChiCTR-IPR-15006879. Registered on 5 August 2015.

Abstract Background A large number of randomized trials on the use of acupuncture to treat chronic pain have been conducted. However, there is considerable controversy regarding the effectiveness of acupuncture. We designed a randomized trial involving patients with chronic neck pain (CNP) to investigate whether acupuncture is more effective than a placebo in treating CNP. Methods/design A five-arm, parallel, single-blinded, randomized, sham-controlled trial was designed. Patients with CNP of more than 3 months’ duration are being recruited from Guangdong Provincial Hospital of Chinese Medicine (China). Following examination, 175 patients will be randomized into one of five groups (35 patients in each group) as follows: a traditional acupuncture group (group A), a shallow-puncture group (group B), a non-acupoint acupuncture group (group C), a non-acupoint shallow-puncture group (group D) and a sham-puncture group (group E). The interventions will last for 20 min and will be carried out twice a week for 5 weeks. The primary outcome will be evaluated by changes in the Northwick Park Neck Pain Questionnaire (NPQ). Secondary outcomes will be measured by the pain threshold, the Short Form McGill Pain Questionnaire-2 (SF-MPQ-2), the 36-Item Short-Form Health Survey (SF-36) and diary entries. Analysis of the data will be performed at baseline, at the end of the intervention and at 3 months’ follow-up. The safety of acupuncture will be evaluated at each treatment period. Discussion The purpose of this trial is to determine whether traditional acupuncture is more effective for chronic pain relief than sham acupuncture in adults with CNP, and to determine which type of sham acupuncture is the optimal control for clinical trials. Trial registration Chinese Clinical Trial Registry: ChiCTR-IOR-15006886 . Registered on 2 July 2015.

Background: Femoral hernias are less common than inguinal hernias. The use of preformed mesh to repair femoral hernias without tension has become increasingly common. We sought to investigate the safety and feasibility of repairing femoral hernias with a Prolene 3-dimensional (3-D) patch using a femoris approach. Methods:We identified all consecutive patients with femoral hernias treated at our centre with a Prolene 3-D patch using a femoris approach in our institution over a 5-year period (2004-2009). We assessed duration of surgery, length of stay in hospital, recurrence, postoperative pain and complications. Results: We repaired 73 hernias with this technique during the study period. The mean duration of surgery was 13.1 minutes, most patients were discharged in less than 24 hours, no recurrence was noted, and only minor complications occurred. Conclusion: This technique has not only the same advantage of other tension-free repairs, but also the advantages of convenience and shorter duration of surgery. [ABSTRACT FROM AUTHOR]