Versatile Polymerization-Induced Emission Polymers from Barbier Polymerization of Cinnamic Esters with Tunable Emission.

Cinnamic ester is a common and abundant chemical substance, which can be extracted from natural plants. Compared with traditional esters, cinnamic ester contains α,ß-unsaturated carbonyl structure with multiple reactive sites, resulting in more abundant reactivities and chemical structures. Here, a versatile polymerization-induced emission (PIE) is successfully demonstrated through Barbier polymerization of cinnamic ester. Attributed to its abundant reactivities of α,ß-unsaturated carbonyl structure, Barbier polymerization of cinnamic esters with different organodihalides gives polyalcohol and polyketone via 1,2-addition and 1,4-addition, respectively, which is also confirmed by small molecular model reactions. Meanwhile, these organodihalides dependant polyalcohol and polyketone exhibit different non-traditional intrinsic luminescence (NTIL) from aggregation-induced emission (AIE) type to aggregation-caused quenching (ACQ) type, where novel PIE luminogens (PIEgens) are revealed. Further potential applications in explosive detection are carried out, where it achieves TNT detection sensitivity at ppm level in solution and ng level on the test paper. This work therefore expands the structure and functionality libraries of monomer, polymer and NTIL, which might cause inspirations to different fields including polymer chemistry, NTIL, AIE and PIE.

Clickable Polymerization-Induced Emission Luminogens Toward Color-Tunable Modification of Non-Traditional Intrinsic Luminescent Polymers.

Non-traditional intrinsic luminescent (NTIL) polymer is an emerging field, and its color-tunable modification is highly desirable but still rarely investigated. Here, a click chemistry approach for the color-tunable modifications of NTIL polymers by introducing clickable polymerization-induced emission luminogen (PIEgen), is demonstrated. Through Cu-catalyzed azide-alkyne cycloaddition click chemistry, a series of PIEgens is successful prepared, which is further polymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Interestingly, after clickable modification, these monomers are nonemissive in both solution and aggregation states; while, the corresponding polymers exhibit intriguing aggregation-induced emission (AIE) characteristics, confirming their PIEgen characteristics. By varying alkynyl substitutions, color-tunable NTIL polymers are achieved with emission wavelength varying from 448 to 498 nm, revealing a series of PIEgens and verifying the importance of modification of NTIL polymers. Further luminescence energy transfer application is carried out as well. This work therefore designs a series of clickable PIEgens and opens a new avenue for the modification of NTIL polymers via click chemistry, which may cause inspirations to the research fields including luminescent polymer, NTIL, click chemistry, AIE and modification.

Effectiveness of perioperative low-dose esketamine infusion for postoperative pain management in pediatric urological surgery: a prospective clinical trial.

BACKGROUND: Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. METHODS: Pediatric patients (n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. RESULTS: In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group (P < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively (P = 0.021). CONCLUSIONS: The use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry- ChiCTR2300073879 (24/07/2023).

Contribution of DNMT1 to Neuropathic Pain Genesis Partially through Epigenetically Repressing Kcna2 in Primary Afferent Neurons.

Expressional changes of pain-associated genes in primary sensory neurons of DRG are critical for neuropathic pain genesis. DNA methyltransferase (DNMT)-triggered DNA methylation silences gene expression. We show here that DNMT1, a canonical maintenance methyltransferase, acts as the de novo DNMT and is required for neuropathic pain genesis likely through repressing at least DRG Kcna2 gene expression in male mice. Peripheral nerve injury upregulated DNMT1 expression in the injured DRG through the transcription factor cAMP response element binding protein-triggered transcriptional activation of Dnmt1 gene. Blocking this upregulation prevented nerve injury-induced DNA methylation within the promoter and 5'-untranslated region of Kcna2 gene, rescued Kcna2 expression and total Kv current, attenuated hyperexcitability in the injured DRG neurons, and alleviated nerve injury-induced pain hypersensitivities. Given that Kcna2 is a key player in neuropathic pain, our findings suggest that DRG DNMT1 may be a potential target for neuropathic pain management.SIGNIFICANCE STATEMENT In the present study, we reported that DNMT1, a canonical DNA maintenance methyltransferase, is upregulated via the activation of the transcription factor CREB in the injured DRG after peripheral nerve injury. This upregulation was responsible for nerve injury-induced de novo DNA methylation within the promoter and 5'-untranslated region of the Kcna2 gene, reductions in Kcna2 expression and Kv current and increases in neuronal excitability in the injured DRG. Since pharmacological inhibition or genetic knockdown of DRG DNMT1 alleviated nerve injury-induced pain hypersensitivities, DRG DNMT1 contributes to neuropathic pain genesis partially through repression of DRG Kcna2 gene expression.

Neuropeptide Y1 Receptor Antagonist Alters Gut Microbiota and Alleviates the Ovariectomy-Induced Osteoporosis in Rats.

A plethora of evidence has suggested that gut microbiota is involved in the occurrence and development of postmenopausal osteoporosis (PMO). It has been suggested that neuropeptide Y (NPY) modulates the bone metabolism through Y1 receptor (Y1R), and might be associated with gut microbiota. The present study aims to evaluate the anti-osteoporotic effects of Y1R antagonist and to investigate the potential mechanism by which Y1R antagonist regulates gut microbiota. In this study, eighteen female rats were randomly divided into three groups: the sham surgery (SHAM) group, the ovariectomized (OVX) group, and OVX+BIBO3304 group. After 6 weeks following surgery, Y1R antagonist BIBO3304 was administered to the rats in OVX+BIBO3304 group for 7 days. The bone microstructure and serum biochemical parameters were measured at 12 weeks after operation. The differences in the gut microbiota were analyzed by 16S rDNA gene sequencing. Heat-map and Spearman's correlation analyses were constructed to investigate the correlations between microbiota and bone metabolism-related parameters. The results indicated that OVX+BIBO3304 group showed significantly higher BMD, BV/TV, Tb.Th, Tb.N, Conn.D, and serum Ca2+ level than those in OVX group. Additionally, Y1R antagonist changed the gut microbiota composition with lower Firmicutes/Bacteroidetes ratio and higher proportions of some probiotics, including Lactobacillus. The correlation analysis showed that the changes of gut microbiota were closely associated with bone microstructure and serum Ca2+ levels. Our results suggested that Y1R antagonist played an anti-osteoporotic effect and regulated gut microbiota in OVX rats, indicating the potential to utilize Y1R antagonist as a novel treatment for PMO.

MBD1 Contributes to the Genesis of Acute Pain and Neuropathic Pain by Epigenetic Silencing of Oprm1 and Kcna2 Genes in Primary Sensory Neurons.

The transmission of normal sensory and/or acute noxious information requires intact expression of pain-associated genes within the pain pathways of nervous system. Expressional changes of these genes after peripheral nerve injury are also critical for neuropathic pain induction and maintenance. Methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, regulates gene transcriptional activity. We report here that MBD1 in the primary sensory neurons of DRG is critical for the genesis of acute pain and neuropathic pain as DRG MBD1-deficient mice exhibit the reduced responses to acute mechanical, heat, cold, and capsaicin stimuli and the blunted nerve injury-induced pain hypersensitivities. Furthermore, DRG overexpression of MBD1 leads to spontaneous pain and evoked pain hypersensitivities in the WT mice and restores acute pain sensitivities in the MBD1-deficient mice. Mechanistically, MDB1 represses Oprm1 and Kcna2 gene expression by recruiting DNA methyltransferase DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 is likely a key player under the conditions of acute pain and neuropathic pain.SIGNIFICANCE STATEMENT In the present study, we revealed that the mice with deficiency of methyl-CpG-binding domain protein 1 (MBD1), an epigenetic repressor, in the DRG displayed the reduced responses to acute noxious stimuli and the blunted neuropathic pain. We also showed that DRG overexpression of MBD1 produced the hypersensitivities to noxious stimuli in the WT mice and rescued acute pain sensitivities in the MBD1-deficient mice. We have also provided the evidence that MDB1 represses Oprm1 and Kcna2 gene expression by recruiting DNA methyltransferase DNMT3a into these two gene promoters in the DRG neurons. DRG MBD1 may participate in the genesis of acute pain and neuropathic pain likely through regulating DNMT3a-controlled Oprm1 and Kcna2 gene expression in the DRG neurons.

DNMT3a-triggered downregulation of K2p 1.1 gene in primary sensory neurons contributes to paclitaxel-induced neuropathic pain.

Antineoplastic drugs induce dramatic transcriptional changes in dorsal root ganglion (DRG) neurons, which may contribute to chemotherapy-induced neuropathic pain. K2p 1.1 controls neuronal excitability by setting the resting membrane potential. Here, we report that systemic injection of the chemotherapy agent paclitaxel time-dependently downregulates the expression of K 2p 1.1 mRNA and its coding K2p 1.1 protein in the DRG neurons. Rescuing this downregulation mitigates the development and maintenance of paclitaxel-induced mechanical allodynia and heat hyperalgesia. Conversely, in the absence of paclitaxel administration, mimicking this downregulation decreases outward potassium current and increases excitability in the DRG neurons, leading to the enhanced responses to mechanical and heat stimuli. Mechanically, the downregulation of DRG K 2p 1.1 mRNA is attributed to paclitaxel-induced increase in DRG DNMT3a, as blocking this increase reverses the paclitaxel-induced the decrease of DRG K2p 1.1 and mimicking this increase reduces DRG K2p 1.1 expression. In addition, paclitaxel injection increases the binding of DNMT3a to the K 2p 1.1 gene promoter region and elevates the level of DNA methylation within this region in the DRG. These findings suggest that DNMT3a-triggered downregulation of DRG K2p 1.1 may contribute to chemotherapy-induced neuropathic pain.

Endothelin type A receptors mediate pain in a mouse model of sickle cell disease.

Sickle cell disease is associated with acute painful episodes and chronic intractable pain. Endothelin-1, a known pain inducer, is elevated in the blood plasma of both sickle cell patients and mouse models of sickle cell disease. We show here that the levels of endothelin-1 and its endothelin type A receptor are increased in the dorsal root ganglia of a mouse model of sickle cell disease. Pharmacologic inhibition or neuron-specific knockdown of endothelin type A receptors in primary sensory neurons of dorsal root ganglia alleviated basal and post-hypoxia evoked pain hypersensitivities in sickle cell mice. Mechanistically, endothelin type A receptors contribute to sickle cell disease-associated pain likely through the activation of NF-κB-induced Nav1.8 channel upregulation in primary sensory neurons of sickle cell mice. Our findings suggest that endothelin type A receptor is a potential target for the management of sickle cell disease-associated pain, although this expectation needs to be further verified in clinical settings.

Delayed activation of spinal microglia contributes to the maintenance of bone cancer pain in female Wistar rats via P2X7 receptor and IL-18.

Accumulating evidence suggests that activation of spinal microglia contributes to the development of inflammatory and neuropathic pain. However, the role of spinal microglia in the maintenance of chronic pain remains controversial. Bone cancer pain shares features of inflammatory and neuropathic pain, but the temporal activation of microglia and astrocytes in this model is not well defined. Here, we report an unconventional role of spinal microglia in the maintenance of advanced-phase bone cancer pain in a female rat model. Bone cancer elicited delayed and persistent microglial activation in the spinal dorsal horn on days 14 and 21, but not on day 7. In contrast, bone cancer induced rapid and persistent astrocytic activation on days 7-21. Spinal inhibition of microglia by minocycline at 14 d effectively reduced bone cancer-induced allodynia and hyperalgesia. However, pretreatment of minocycline in the first week did not affect the development of cancer pain. Bone cancer increased ATP levels in CSF, and upregulated P2X7 receptor, phosphorylated p38, and IL-18 in spinal microglia. Spinal inhibition of P2X7/p-38/IL-18 pathway reduced advanced-phase bone cancer pain and suppressed hyperactivity of spinal wide dynamic range (WDR) neurons. IL-18 induced allodynia and hyperalgesia after intrathecal injection, elicited mechanical hyperactivity of WDR neurons in vivo, and increased the frequency of mEPSCs in spinal lamina IIo nociceptive synapses in spinal cord slices. Together, our findings demonstrate a novel role of microglia in maintaining advanced phase cancer pain in females via producing the proinflammatory cytokine IL-18 to enhance synaptic transmission of spinal cord nociceptive neurons.

G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury.

Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia. Blocking these increases rescued dorsal root ganglia Oprm1, Oprk1, and Oprd1 gene expression and morphine or loperamide analgesia and prevented the development of morphine or loperamide-induced analgesic tolerance under neuropathic pain conditions. Conversely, mimicking these increases reduced the expression of three opioid receptors and promoted the mu opioid receptor-gated release of primary afferent neurotransmitters. Mechanistically, nerve injury-induced increases in the binding activity of G9a and H3K9me2 to the Oprm1 gene were associated with the reduced binding of cyclic AMP response element binding protein to the Oprm1 gene. These findings suggest that G9a participates in the nerve injury-induced reduction of the Oprm1 gene likely through G9a-triggered blockage in the access of cyclic AMP response element binding protein to this gene.

Peripheral TGF-ß1 signaling is a critical event in bone cancer-induced hyperalgesia in rodents.

Pain is the most common symptom of bone cancer. TGF-ß, a major bone-derived growth factor, is largely released by osteoclast bone resorption during the progression of bone cancer and contributes to proliferation, angiogenesis, immunosuppression, invasion, and metastasis. Here, we further show that TGF-ß1 is critical for bone cancer-induced pain sensitization. We found that, after the progression of bone cancer, TGF-ß1 was highly expressed in tumor-bearing bone, and the expression of its receptors, TGFßRI and TGFßRII, was significantly increased in the DRG in a rat model of bone cancer pain that is based on intratibia inoculation of Walker 256 mammary gland carcinoma cells. The blockade of TGF-ß receptors by the TGFßRI antagonist SD-208 robustly suppressed bone cancer-induced thermal hyperalgesia on post-tumor day 14 (PTD 14). Peripheral injection of TGF-ß1 directly induced thermal hyperalgesia in intact rats and wide-type mice, but not in Trpv1(-/-) mice. Whole-cell patch-clamp recordings from DRG neurons showed that transient receptor potential vanilloid (TRPV1) sensitivity was significantly enhanced on PTD 14. Extracellular application of TGF-ß1 significantly potentiated TRPV1 currents and increased [Ca(2+)]i in DRG neurons. Pharmacological studies revealed that the TGF-ß1 sensitization of TRPV1 and the induction of thermal hyperalgesia required the TGF-ßR-mediated Smad-independent PKCε and TGF-ß activating kinase 1-p38 pathways. These findings suggest that TGF-ß1 signaling contributes to bone cancer pain via the upregulation and sensitization of TRPV1 in primary sensory neurons and that therapeutic targeting of TGF-ß1 may ameliorate the bone cancer pain in advanced cancer.

Research trends and hotspots on osteoporosis: a decade-long bibliometric and visualization analysis from 2014 to 2023.

Background: Osteoporosis is characterized by diminished bone density and quality, compromised bone microstructure, and increased bone fragility, culminating in a heightened risk of fracture. Relatively few attempts have been made to survey the breadth of osteoporosis research using bibliometric approaches. This study aims to delineate the current landscape of osteoporosis research, offering clarity and visualization, while also identifying potential future directions for investigation. Methods: We retrieved and filtered articles and reviews pertaining to osteoporosis from the Web of Science Core Collection database, specifically the Science Citation Index Expanded (SCI-E) edition, spanning the years 2014 to 2023. Informatics tools such as CiteSpace and VOSviewer were employed to dissect the intellectual framework, discern trends, and pinpoint focal points of interest within osteoporosis research. Results: Our dataset comprised 33,928 osteoporosis-related publications, with a notable surge in annual publication numbers throughout the last decade. China and the United States lead in terms of research output. The University of California System contributed substantially to this body of work, with Amgen demonstrating the highest degree of centrality within the network. Cooper Cyrus emerged as a pivotal figure in the field. An analysis of highly-cited studies, co-citation networks, and keyword co-occurrence revealed that recent years have predominantly concentrated on elucidating mechanisms underlying osteoporosis, as well as its diagnosis, prevention, and treatment strategies. Burst detection analyses of citations and keywords highlighted osteoblasts, sarcopenia, gut microbiota, and denosumab as contemporary hotspots within osteoporosis research. Conclusion: This bibliometric analysis has provided a visual representation of the fundamental knowledge structure, prevailing trends, and key focal areas within osteoporosis research. The identification of osteoblasts, sarcopenia, gut microbiota, and denosumab as current hotspots may guide future research endeavors. Continued efforts directed at understanding the mechanisms, fracture outcomes, diagnostics, and therapeutics related to osteoporosis are anticipated to deepen our comprehension of this complex disease.

Mapping the current trends and hotspots of adult hippocampal neurogenesis from 2004-2023: a bibliometric analysis.

Objective: We utilized bibliometric and data visualization techniques to discern the primary research domains and emerging frontiers in the field of adult hippocampal neurogenesis (AHN). Methods: We systematically searched the Web of Science database for AHN-related articles published between 2004 and 2023. The retrieved articles were filtered based on publication types (articles and reviews) and language (English). We employed CiteSpace, VOSviewer, and the online bibliometric platform (bibliometric.com) to visualize and analyze the collected data. Results: In total, 1,590 AHN-related publications were discovered, exhibiting a steady increase in yearly publications over time. The United States emerged as the leading contributor in AHN research in terms of both publication quantity and national influence. Among all research institutions in the field of AHN, the University of California System exhibited the highest impact. Kempermann, Gerd was the most active author. The publications of the top three active authors primarily focused on the functions of AHN, and reversing hippocampal damage and cognitive impairment by improving AHN. An analysis of reference co-citation clustering revealed 8 distinct research clusters, and the notable ones included "adult hippocampal neurogenesis," "neurogenesis," "hippocampus," "dentate gyrus," "neural stem cell," and "depression." Additionally, a burst keyword detection indicated that 'anxiety' is a current research hotspot in the field of AHN. Conclusion: This in-depth bibliographic assessment of AHN offers a deeper insight into the present research hotspots in the field. The association between AHN and cognitive diseases, such as Alzheimer's disease (AD) and anxiety, has emerged as a prominent research hotspot.

Predicting white-matter hyperintensity progression and cognitive decline in patients with cerebral small-vessel disease: a magnetic resonance-based habitat analysis.

Background: White-matter hyperintensity (WMH) is the key magnetic resonance imaging (MRI) marker of cerebral small-vessel disease (CSVD). This study aimed to investigate whether habitat analysis based on physiologic MRI parameters can predict the progression of WMH and cognitive decline in CSVD. Methods: Diffusion- and perfusion-weighted imaging data were obtained from 69 patients with CSVD at baseline and at 1-year of follow-up. The white-matter region was classified into constant WMH, growing WMH, shrinking WMH, and normal-appearing white matter (NAWM) according to the T2-fluid-attenuated inversion recovery (FLAIR) sequences images at the baseline and follow-up. We employed k-means clustering on a voxel-wise basis to delineate WMH habitats, integrating multiple diffusion metrics and cerebral blood flow (CBF) values derived from perfusion data. The WMH at the baseline and the predicted WMH from the habitat analysis were used as regions of avoidance (ROAs). The decreased rate of global efficiency for the whole brain structural connectivity was calculated after removal of the ROA. The association between the decreased rate of global efficiency and Montreal Cognitive Assessment (MoCA) and mini-mental state examination (MMSE) scores was evaluated using Pearson correlation coefficients. Results: We found that the physiologic MRI habitats with lower fractional anisotropy and CBF values and higher mean diffusivity, axial diffusivity, and radial diffusivity values overlapped considerably with the new WMH (growing WMH of baseline) after a 1-year follow-up; the accuracy of distinguishing growing WMH from NAWM was 88.9%±12.7% at baseline. Similar results were also found for the prediction of shrinking WMH. Moreover, after the removal of the predicted WMH, a decreased rate of global efficiency had a significantly negative correlation with the MoCA and MMSE scores at follow-up. Conclusions: This study revealed that a habitat analysis combining perfusion with diffusion parameters could predict the progression of WMH and related cognitive decline in patients with CSVD.

The kynurenine pathway regulated by intestinal innate lymphoid cells mediates postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD.

Mapping the current trends and hotspots of vascular cognitive impairment from 2000-2021: A bibliometric analysis.

AIMS: To visualize the trends and hotspots in the scientific research related to vascular cognitive impairment (VCI) quantitatively and qualitatively. METHODS: Cross-sectional bibliometric analysis of publications that related to VCI was conducted. Publications were found by searching in the Web of Science Core Collection database (WoSCC) - Edition: Science Citation Index Expanded (SCI-Expanded) from January 2000 to December 2021. Publication type was restricted to article and review in the English language. The downloaded data were screened and analyzed in January 2022. RESULTS: In total, 16,264 publications were identified, with a steady increase in annual publications. The United States was the leading country in VCI research regarding publication numbers and national influence. National Institute of Aging had the highest influence among all the institutes in the field of VCI. Philip Scheltens was the most active author. The top five active authors' publications focused on pathobiology, neuroimaging standards, risk factors, prevention, and the standard diagnosis of vascular dementia (VaD). A co-cited publication clustering resulted in 19 main clusters, and the prevention, blood-brain barrier, cholesterol, cerebral amyloid angiopathy, and VaD were the top 5 clusters. Moreover, burst keywords detection revealed that the "small vessel disease" is the current hotspot in the field of VCI. CONCLUSIONS: This bibliometric analysis mapped the overall research structure of VCI and analyzed the current research trends and hotspots for future studies orientation. Neuroimaging, risk factors detection, and pathobiology are the current trends in VCI research. Small vessel disease and its mechanisms are the current hotspots of VCI research.

Potential novel therapeutic strategies for neuropathic pain.

Purpose: To explore the potential therapeutic strategies of different types of neuropathic pain (NP) and to summarize the cutting-edge novel approaches for NP treatment based on the clinical trials registered on ClinicalTrials.gov. Methods: The relevant clinical trials were searched using ClinicalTrials.gov Dec 08, 2022. NP is defined as a painful condition caused by neurological lesions or diseases. All data were obtained and reviewed by the investigators to confirm whether they were related to the current topic. Results: A total of 914 trials were included in this study. They were divided into painful diabetic neuropathy (PDN), postherpetic neuralgia (PHN), sciatica (SC), peripheral nerve injury-related NP (PNI), trigeminal neuralgia (TN), chemotherapy-induced NP (CINP), general peripheral NP (GPNP) and spinal cord injury NP (SCI-NP). Potential novel therapeutic strategies, such as novel drug targets and physical means, were discussed for each type of NP. Conclusion: NP treatment is mainly dominated by drug therapy, and physical means have become increasingly popular. It is worth noting that novel drug targets, new implications of conventional medicine, and novel physical means can serve as promising strategies for the treatment of NP. However, more attention needs to be paid to the challenges of translating research findings into clinical practice.

Maxillary nerve compression in cynomolgus monkey Macaca fascicularis: altered somatic sensation and peripheral nerve firing.

BACKGROUND: Trigeminal nerve is a major source of the sensory input of the face, and trigeminal neuropathology models have been reported in rodents with injury to branches of the maxillary or mandibular division of the trigeminal nerve. Non-human primates are neuroanatomically more closely related to human than rodents; however, nerve injury studies in non-human primates are limited. RESULTS: We describe here a nerve injury model of maxillary nerve compression (MNC) in the cynomolgus macaque monkey, Macaca fascicularis, and the initial characterization of the consequences of damage to this trigeminal nerve branch. The nerve injury from the compression appeared to be mild, as we did not observe overt changes in home-cage behavior in the monkeys. When mechanical stimulation was applied to the facial area, monkeys with MNC displayed increased mechanical sensitivity, as the avoidance response scores were lower than those from the control animals. Such a change in mechanical sensitivity appeared to be somewhat bilateral, as the contralateral side also showed increased mechanical sensitivity, although the change on the ipsilateral side was more robust. Multiple-unit recording of the maxillary nerve showed a general pattern of increasing responsiveness to escalating force in mechanical stimulation on the contralateral side. Ipsilateral side of the maxillary nerve showed a lack of responsiveness to escalating force in mechanical stimulation, possibly reflecting a maximum stimulation threshold effect from sensitized nerve due to MNC injury. CONCLUSIONS: These results suggest that MNC may produce increased sensitivity of the ipsilateral maxillary nerve, and that this model may serve as a non-human primate model to evaluate the effect of injury to trigeminal nerve branches.

Research Trends and Hotspots on Herpes Zoster: A 10-Year Bibliometric Analysis (2012-2021).

Purpose: Herpes zoster infection, with its considerable burden to individuals and society, remains a challenge around the world. However, to the knowledge of the authors, little bibliometric quantitative or qualitative analysis has been carried out to evaluate herpes zoster research. This study aimed to use a bibliometric analysis to evaluate current publication trends and hotspots on herpes zoster research worldwide, in order to advance research in this field. Methods: Relevant publications from January 2012 to December 2021 were collected from the Web of Science Core Collection database. Citespace (V5.8.R3) was used to analyze the research points, including publication countries, institutions and authors, cited author, cited reference and their clustering, and keyword co-occurrence, and burst keyword to acquire research trends and hotspots. Results: A total of 9,259 publications were obtained, with a steady increase in the number of annual publications during the decade. Articles were the main type of publication. The United States is the leading country in this research, and the University of Colorado has the highest influence in this field. Oxman is the most representative author, with a main research interest in herpes zoster vaccines. The top five cited authors' publications focused on herpes zoster vaccines, molecular mechanisms, and postherpetic neuralgia. A co-citation map resulted 19 main clusters, and revealed that vaccines, postherpetic neuralgia, treatments, varicella zoster virus and its mechanisms, and epidemiology of herpes zoster were the current research focus after clustering co-cited publications. Human herpesviruses, antiviral prophylaxis, rheumatoid arthritis, recombinant zoster vaccine, varicella vaccination and postherpetic neuralgia were the top clusters after co-occurrence keywords analysis. Moreover, burst keywords detection showed that the subunit vaccine was the new hotspot in the field of herpes zoster. Conclusion: This bibliometric study defined the overall prospects in the field of herpes zoster and provided valuable instruction for the ongoing research. The keyword "subunit vaccine" indicated that a vaccine for herpes zoster prevention was the hotspot. Efforts to prevent varicella zoster virus infection will be essential to improve herpes zoster outcomes.

Emerging Trends and Hot Spots in Sepsis-Associated Encephalopathy Research From 2001 to 2021: A Bibliometric Analysis.

Study Objectives: To evaluate sepsis-associated encephalopathy (SAE) research and to quantitatively and qualitatively predict research hot spots using bibliometric analysis. Methods: We extracted relevant publications from the Web of Science Core Collection on July 28, 2021. We investigated the retrieved data by bibliometric analysis (e.g. co-cited and cluster analysis, keyword co-occurrence) using the software CiteSpace and VOSviewer, the Online Analysis Platform of Literature Metrology (http://bibliometric.com/) and Bibliometrix to analyse and predict the trends and hot spots in this field. Main Results: We identified 1,582 published articles and reviews on SAE from 2001 to 2021. During this period, the number of manuscripts on SAE increased steadily and peaked in 2021. The USA and China were the leading countries that had a critical impact on SAE research. Among all institutions, Vanderbilt University and Pittsburgh University held leading positions and became central in the collaboration network. Among all the journals, Critical Care Medicine published the maximum number of manuscripts in the field of SAE within 20 years. Dal-Pizzol Felipe was the most productive author (61 papers) and received the largest number of citations (930 citations). Co-citation cluster analysis revealed that the most popular terms on SAE in the manner of cluster labels were critical illness, sepsis-associated encephalopathy, polymicrobial sepsis, posterior reversible encephalopathy syndrome, rat brain, intensive care unit, prior sepsis, molecular hydrogen, inflammation drive, metabolic encephalopathies, delirium pathophysiology, and clinical neuroscience. Keyword burst detection indicated that neuroinflammation, blood-brain barrier (BBB) and mitochondria dysfunction were the current research hot spots. Conclusions: Our study revealed that neuroinflammation, blood-brain barrier, and mitochondria dysfunction had been the research foci of SAE over the past 20 years. These have emerged as the basis for transformation from basic research to clinical application in finding effective methods for the prevention and treatment of SAE.