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Abstract Background Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. Methods Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. Results We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. Conclusion These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.

One potential cause of cancer is genomic instability that arises in normal cells due to years of DNA damage in the body. The clinical application of radiotherapy and cytotoxic drugs to treat cancer is based on the principle of damaging the DNA of cancer cells. However, the benefits of these treatments also have negative effects on normal tissue. While there have been notable advancements in molecular-driven therapy and immunotherapy for colorectal cancer (CRC), a considerable portion of patients with advanced CRC do not experience any benefits from these treatments, leading to a poor prognosis. In recent years, targeted therapy aimed at suppressing the DNA damage response (DDR) in cancer cells has emerged as a potential treatment option for CRC patients, offering them more choices for treatment. Currently, the integration of DDR and clinical intervention remains in the exploratory phase. This review primarily elucidates the fundamental principles of DDR inhibitors, provides an overview of their current clinical application status in CRC, and discusses the advancements as well as limitations observed in relevant studies.

Objective: Patients undergoing percutaneous transforaminal endoscopic discectomy (PTED) often complain of unbearable intraoperative pain. This study is to observe clinical effectiveness and safety of intradiscal local anesthetic injection for intraoperative pain relief. Methods: Total 268 patients who underwent PTED were analyzed. Patients were divided into intradiscal saline injection group (group C) and intradiscal local anesthetic injection group (group L). Intradiscal mixture was consisted of saline or local anesthetic + methylene blue, the amount of injected mixture was 3 mL. Demographic data, visual analog scale (VAS) and Quebec Back Pain Disability Scale (QBPDS) scores, mean arterial pressure (MAP) and heart rate (HR), total dosage of fentanyl, satisfaction rate of anesthesia and complications were collected at different timepoints. Results: Compared with group C (3.94 ± 0.57), there was a significant reduction of VAS in group L (2.83 ± 0.28) during fibrous annular operation phase (T2). Group L had a lower total dosage of fentanyl (71 [63, 78] μg) and a higher anesthesia satisfaction rate (95.3%) than group C (82 [70, 132] μg and 73.6%, respectively) (P

Parkinson’s disease is a severe neurodegenerative disorder. Currently, deep brain electrical stimulation (DBS) is the first line of surgical treatment. However, serious neurological impairments such as speech disorders, disturbances of consciousness, and depression after surgery limit the efficacy of treatment. In this review, we summarize the recent experimental and clinical studies that have explored the possible causes of neurological deficits after DBS. Furthermore, we tried to identify clues from oxidative stress and pathological changes in patients that could lead to the activation of microglia and astrocytes in DBS surgical injury. Notably, reliable evidence supports the idea that neuroinflammation is caused by microglia and astrocytes, which may contribute to caspase-1 pathway-mediated neuronal pyroptosis. Finally, existing drugs and treatments may partially ameliorate the loss of neurological function in patients following DBS surgery by exerting neuroprotective effects.

PurposeTo summarize the classification of computerized cognitive assessment (CCA) tools for assessing stroke patients, to clarify their benefits and limitations, and to reveal strategies for future studies on CCA tools.MethodsA literature review was performed using PubMed, Embase, Scopus, JAMA Network, Cochrane Library and PsycINFO databases from January 1st, 2010, to August 1st, 2022. Two authors independently screened the literature following the same criteria, evaluated the study quality, and collected data from the articles.ResultsA total of 8,697 papers were acquired from the six databases. A total of 74 potentially eligible articles were selected for review. Of these, 29 articles were not relevant to this research, 3 were reviews, 2 were not written in English, and 1 was on an ongoing trial. By screening the references of the reviews, 3 additional articles were included in this study. Thus, a total of 42 articles met the criteria for the review. In terms of the CCA tools analyzed in these studies, they included five types: virtual reality (VR)-based, robot-based, telephone-based, smartphone-based, and computer-based cognitive assessments. Patients' stages of the disease ranged from the subacute phase and rehabilitation phase to the community phase. A total of 27 studies supported the effectiveness of CCA tools, while 22 out of 42 articles mentioned their benefits and 32 revealed areas for future improvement of CCA tools.ConclusionsAlthough the use of CCA tools for assessing the cognition of post-stroke patients is becoming popular, there are still some limitations and challenges of using such tools in stroke survivors. More evidence is thus needed to verify the value and specific role of these tools in assessing the cognitive impairment of stroke patients.

AbstractIn this study, 864 heat transfer experimental data points and 216 pressure drop experimental data points were used to compare the heat transfer and friction factor behavior of 3D-printed and traditional tubes under uniform wall heat flux boundary condition. Experiments were conducted in the entire flow region that covers laminar, transition, and turbulent regions. The inside diameter of the test tubes is around 2 mm, and the average inside wall surface roughness for traditional and 3D-printed tubes is 2.211 μm and 35.249 μm, respectively. Comparing with the traditional tubes, in the upper transition and the turbulent regions, the Nusselt numbers and Colburn j-factors of the 3D-printed tube under three different flow directions were enhanced by an average of 52.67% and 51.59% respectively. The greater relative roughness of the 3D-printed tube enhanced the heat transfer but also increased the pressure drop significantly. The friction factors for the 3D-printed tube in these regions also increased by an average of 154.44% compared with the traditional tube. The results also show that the effect of different flow directions on heat transfer and pressure drop of the 3D-printed tube is insignificant relative to roughness. Moreover, the 3D-printed tube has an earlier transition compared with the traditional tube. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Alicyclobacillus acidoterrestris is a common microorganism in fruit juice. It can produce off‐odor metabolites and has been considered to be an important factor in juice contamination. Thus, the development of new strategy for the control of A. acidoterrestris has important practical significance. The primary objective of this work was to assess the antibacterial performance of ε‐polylysine‐functionalized magnetic composites (Fe3O4@MoS2@PAA‐EPL) in apple juice and its effect on juice quality. Moreover, the molecular mechanism of Fe3O4@MoS2@PAA‐EPL against A. acidoterrestris was explored by RNA sequencing (RNA‐Seq).Experimental results indicated that the synthesized composites possessed the ability to inhibit the viability of A. acidoterrestris vegetative cells and spores. Besides, investigation on the quality of apple juice incubated with Fe3O4@MoS2@PAA‐EPL implied that the fabricated composites displayed negligible adverse effects on juice quality. In addition, the results of RNA‐Seq demonstrated that 833 differentially expressed genes (DEGs) were identified in Fe3O4@MoS2@PAA‐EPL‐treated A. acidoterrestris, which were associated with translation, energy metabolism, amino acid metabolism, membrane transport and cell integrity.These results suggested that the treatment of Fe3O4@MoS2@PAA‐EPL disrupted energy metabolism, repressed cell wall synthesis and caused membrane transport disorder of bacterial cells. This work provides novel insights into the molecular antibacterial mechanism for ε‐polylysine‐functionalized magnetic composites against A. acidoterrestris. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]