Functional dissection of parabrachial substrates in processing nociceptive information.

Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( NK1R) (lPBN NK1R) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN NK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN NK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

Factors influencing the posterior cruciate ligament buckling phenomenon-a multiple linear regression analysis of bony and soft tissue structures of the knee joint.

PURPOSE: To determine whether posterior cruciate ligament (PCL) buckling (angular change) is associated with anterior cruciate ligament (ACL) status (intact or ruptured), meniscal bone angle (MBA), anterior tibial translation (ATT), body weight, femoral-tibial rotation (FTR), posterior tibial slope (PTS), PCL length and femoral-tibial distance (FTD) and to identify the factors that have the greatest influence. METHODS: All enrolled participants were scanned with a 3.0 T, 8-channel coil MRI system (Magnetom Verio; Siemens). Bone and soft tissue parameters were measured by MIMICS software for each subject and each measured parameter was correlated with PCL buckling phenomena. The correlated and statistically significant parameters were then analyzed by multiple linear regression to determine the magnitude of the effect of the different parameters on the PCL buckling phenomenon. RESULTS: A total of 116 subjects (50 ACL ruptured and 66 age, weight and height matched volunteers with uninjured knees) were enrolled. Among all measured parameters, there were 8 parameters that correlated with PCL angle (PCLA), of which ACL status had the strongest correlation with PCLA (r = - 0.67, p = < 0.001); and 7 parameters that correlated with PCL-posterior femoral cortex angle (PCL-PCA), of which ATT had the strongest correlation with PCL-PCA (r = 0.69, p = < 0.001). PCLIA was not significantly correlated with any of the measured parameters. Multiple linear regression analyses revealed four parameters can explain PCLA, of which ACL status had the strongest effect on PCLA (absolute value of standardized coefficient Beta was 0.508). Three parameters can explain PCL-PCA, of which ATT had the strongest effect on PCLIA (r = 0.69, p = < 0.001), ATT has the greatest effect on PCL-PCA (absolute value of normalized coefficient Beta is 0.523). CONCLUSIONS: PCLA may be a simple and easily reproducible and important supplement for the diagnosis of ACL injury; PCL-PCA is a simple and easily reproducible and important complementary tool for the detection of ATT. The use of PCLA is more recommended to aid in the diagnosis of ACL injury.

Timing dependent neuronal migration is regulated by Cdk5-mediated phosphorylation of JIP1.

The mammalian brain, especially the cerebral cortex, has evolved to increase in size and complexity. The proper development of the cerebral cortex requires the coordination of several events, such as differentiation and migration, that are essential for forming a precise six-layered structure. We have previously reported that Cdk5-mediated phosphorylation of JIP1 at T205 modulates axonal out-growth. However, the spatiotemporal expression patterns and functions of these three genes (Cdk5, Cdk5r1 or p35, and Mapk8ip1 or JIP1) in distinct cell types during cortical development remain unclear. In this study, we analyzed single-cell RNA-sequencing data of mouse embryonic cortex and discovered that Cdk5, p35, and JIP1 are dynamically expressed in intermediate progenitors (IPs). Pseudotime analysis revealed that the expression of these three genes was concomitantly upregulated in IPs during neuronal migration and differentiation. By manipulating the expression of JIP1 and phospho-mimetic JIP1 using in utero electroporation, we showed that phosphorylated JIP1 at T205 affected the temporal migration of neurons.

In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke.

JOURNAL/nrgr/04.03/01300535-202410000-00025/figure1/v/2024-02-06T055622Z/r/image-tiff In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1 (PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.eB-GFAP-shPTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-shPTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

Race and Gender Differences in Anterior Cruciate Ligament Femoral Footprint Location and Orientation: A 3D-MRI Study.

OBJECTIVE: The femoral tunnel position is crucial to anatomic single-bundle anterior cruciate ligament (ACL) reconstruction, but the ideal femoral footprint position are mostly based on small-sized cadaveric studies and elderly patients with a single ethnic background. This study aimed to identify potential race- or gender-specific differences in the ACL femoral footprint location and ACL orientation, determine the correlation between the ACL orientation and the femoral footprint location. METHODS: Magnetic resonance images (MRIs) of 90 Caucasian participants and 90 matched Chinese subjects were used for reconstruction of three-dimensional (3D) femur and tibial models. ACL footprints were sketched by several experienced orthopedic surgeons on the MRI photographs. The anatomical coordinate system was applied to reflect the ACL footprint location and orientation of scanned samples. The femoral ACL footprint locations were represented by their distance from the origin in the anteroposterior (A/P) and distal-proximal (D/P) directions. The orientation of the ACL was described with the sagittal, coronal and transverse deviation angles. The ACL orientation and femoral footprint position were compared by the two-sided t-test. Multiple regression analysis was used to study the correlation between the orientation and femoral footprint position. RESULTS: The average femur footprint A/P position was -6.6 ± 1.6 mm in the Chinese group and -5.1 ± 2.3 mm in the Caucasian group, (p < 0.001). The average femur footprint D/P position was -2.8 ± 2.4 mm in Chinese and - 3.9 ± 2.0 mm in Caucasians, (p = 0.001). The Chinese group had a mean difference of a 1.5 mm (6.1%) more posterior and 1.1 mm (5.3%) more proximal in the position from the flexion-extension axis (FEA). And the males have a sagittal plane elevation about 4-5° higher than females in both racial groups. Furthermore, for every 1% (0.40 mm) increase in A/P and D/P values, the sagittal angle decreased by about 0.12° and 0.24°, respectively; the coronal angle decreased by about 0.10° and 0.30°, respectively. For every 1% (0.40 mm) increase in D/P value, the transverse angle increased by about 0.14°. CONCLUSION: The significant race- and gender-specific differences in the femoral footprint and orientation of the ACL should be taken in consideration during anatomic single-bundle ACL reconstruction. Furthermore, the quantitative relationship between the ACL orientation and the footprint location might provide some reference for surgeons to develop a surgical strategy in ACL single-bundle reconstruction and revision.

Summary of best evidence for self-management in postoperative osteoporotic fracture patients.

Osteoporotic fracture as a serious complication of osteoporosis which is usually treated surgically, and its recovery is closely related to one's own behavior and lifestyle, and is a long-term, complex management process that often requires the individual to self-manage many health-related factors. OBJECTIVE: To gather and synthesize the most robust evidence regarding self-management in patients with postoperative osteoporotic fractures, in order to provide scientific, evidence-based guidance for clinical healthcare professionals to assist postoperative patients in self-management efforts, and to assist patients in optimizing their self-management practices and behavioral norms. METHODS: Based on the "6 S" pyramid model of evidence resources (System, Summaries, Synopses of synthesis, Syntheses, Synopses of studies, Studies), we searched the Up To Date, BMJ Best Practice, The Cochrane Library, Australian Joanna Briggs Institute JBI Evidence-Based Medicine Center Healthcare Database, National Institute for Health and Clinical Excellence (NICE), Guidelines International Network (GIN), National Guideline Clearinghouse (NGC) and Scottish Intercollegiate Guide lines Network (SIGN), MedPulse, Embase, PubMed, CINAHL, Web of Science, SinoMed, Chinese Medical Journal Full Text Database, CNKI, Wanfang Data Knowledge Service Platform, and VIP database, etc, The search period for clinical decision-making, systematic evaluation, clinical guidelines, evidence summaries and expert consensus on self-management of postoperative osteoporotic fracture patients, and it was from the establishment of the database to 18 February 2023. To ensure the quality of the literature, three researchers strictly screened the literature according to the literature inclusion and exclusion criteria, and two or more researchers independently evaluated the quality of the included literature, and extracted and integrated the relevant evidence. RESULTS: Thirteen documents were finally included, including 4 clinical practice guidelines, 5 expert consensus, 2 recommended practices, 1 systematic evaluation, and 1 clinical decision report. The research team summarized the evidence in 6 dimensions: multidisciplinary teamwork, management of daily living, management of treatment adherence, management of exercise, management of fall prevention and subsequent fracture, and management of emotions, and 33 pieces of evidence were extracted. CONCLUSION: The study summarized 33 best evidence of self-management in postoperative osteoporotic fracture patients, which provides a scientific and reasonable self-management program for postoperative patients, and also provides important reference and information for clinical healthcare professionals to provide more comprehensive and scientific self-management health education to patients.

Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by enigmatic pathogenesis. Polyunsaturated fatty acids (PUFAs) are implicated in RA's development and progression, yet their exact mechanisms of influence are not fully understood. Soluble epoxide hydrolase (sEH) is an enzyme that metabolizes anti-inflammatory epoxy fatty acids (EpFAs), derivatives of PUFAs. In this study, we report elevated sEH expression in the joints of CIA (collagen-induced arthritis) rats, concomitant with diminished levels of two significant EpFAs. Additionally, increased sEH expression was detected in both the synovium of CIA rats and in the synovium and fibroblast-like synoviocytes (FLS) of RA patients. The sEH inhibitor TPPU attenuated the migration and invasion capabilities of FLS derived from RA patients and to reduce the secretion of inflammatory factors by these cells. Our findings indicate a pivotal role for sEH in RA pathogenesis and suggest that sEH inhibitors offer a promising new therapeutic strategy for managing RA.

Mesenchymal stem-cell-derived microvesicles ameliorate MPTP-induced neurotoxicity in mice: a role of the gut-microbiota-brain axis.

RATIONALE: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. Increasing evidence suggests the role of the gut-microbiota-brain axis in the pathogenesis of PD. Mesenchymal stem-cell-derived microvesicles (MSC-MVs) have emerged as a therapeutic potential for neurological disorders over the last years. OBJECTIVE: The objective of this study was to investigate whether MSC-MVs could improve PD-like neurotoxicity in mice after administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). RESULTS: MPTP-induced reductions in the dopamine transporter and tyrosine hydroxylase expressions in the striatum and substantia nigra (SNr) were attenuated after a subsequent single administration of MSC-MVs. Increases in the phosphorylated α-synuclein (p-α-Syn)/α-Syn ratio in the striatum, SNr, and colon after MPTP injection were also attenuated after MSC-MVs injection. Furthermore, MSC-MVs restored MPTP-induced abnormalities of the gut microbiota composition. Interestingly, positive correlations between the genus Dubosiella and the p-α-Syn/α-Syn ratio were observed in the brain and colon, suggesting their roles in the gut-microbiota-brain communication. Moreover, MSC-MVs attenuated MPTP-induced reduction of the metabolite, 3,6-dihydroxy-2-[3-methoxy-4-(sulfooxy)phenyl]-7-(sulfinooxy)-3,4-dihydro-2H-1-benzopyran-5-olate, in the blood. Interestingly, a negative correlation between this compound and the p-α-Syn/α-Syn ratio was observed in the brain and colon. CONCLUSIONS: These data suggest that MSC-MVs could ameliorate MPTP-induced neurotoxicity in the brain and colon via the gut-microbiota-brain axis. Therefore, MSC-MVs would have a new therapeutic potential for neurological disorders such as PD.

Individualized Management of Quality of Care in Orthopedic Nurses Based on Sensitive Indicators.

Background: Sensitive indicators of nursing quality focus on the core elements of nursing quality management. Nursing-sensitive quality indicators will play an increasingly important role in the macro and micro management of nursing quality in my country. Objective: This study were aimed at formulating the sensitive index management of orthopedic nursing quality based on individual nurses for improvement of the quality of orthopedic nursing. Methods: Based on the previous literature, the existing challenges in the early application of the orthopedic nursing quality evaluation index were summarized. Moreover, the management system of the orthopedic nursing quality-sensitive index based on individual nurses was devised and implemented, including monitoring the structure and result indices of individual nurses on duty and sampling the process indicators of patients managed by individual nurses. At the quarter-end, the data analysis was performed and fed back to determine the key points of the changes in the quality of specialized nursing affecting the individual, and the PDCA method was utilized for persistent improvement. The changes of sensitive indices of orthopedic nursing quality before (July-December 2018) and 6 months after implementation (July-December 2019) were compared. Results: There were significant differences in other indices (accuracy of limb blood circulation assessment/accuracy of pain assessment/postural care pass rate/accuracy of rehabilitation behavioral training/satisfaction of discharged patients) (P < 0.05). Conclusion: The formulation of an individual-based orthopedic nursing quality-sensitive index management system modifies the traditional quality management model, improves the specialized nursing level, contributes to the accurate core competence training of specialized nursing, and improves the quality of specialized nursing of individual nurses. Consequently, there is an overall improvement in the specialized nursing quality of the department, and fine management is attained.

Novel mutations in the ABCD1 gene caused adrenomyeloneuropathy in the Chinese population.

Background: As a rare genetic disease, adrenomyeloneuropathy (AMN) is the most common adult phenotype of X-linked adrenoleukodystrophy (X-ALD). Mutations in the ABCD1 gene have been identified to cause AMN. Methods: We applied clinical evaluation, laboratory tests, and neuroimaging on three patients with progressive spastic paraparesis. In genetic analysis, we investigated ABCD1 gene mutations by whole-exome sequencing and Sanger sequencing. Bioinformatics tools were used to predict the effects of identified ABCD1 mutations on the protein. Results: All three patients were men with adult-onset disease, mainly characterized by progressive spastic paraparesis. Among them, two patients had peripheral neuropathy and one patient had signs of adrenal insufficiency. All three patients showed cerebral involvement on brain MRI, while two patients were found with diffuse cord atrophy on spinal MRI. High-VLCFA levels in plasma, as well as C24:0/C22:0 and C26:0/C22:0 ratios, were found in all three patients. In addition, three different ABCD1 mutations were identified in three unrelated Chinese families, including one known mutation (c.1415_1416delAG) and two novel mutations (c.217C>T and c.160_170delACGCAGGAGGC). Based on the clinical assessment, radiographic, biochemical, and genetic testing, the final diagnosis was AMN in these patients with spastic paraparesis. Conclusion: This study reported three patients with AMN and identified two novel mutations in the ABCD1 in the Chinese population. Our finding emphasized that X-ALD is an important cause of adult-onset spastic paraplegia. Thus, neuroimaging, VLCFA testing, and especially the detection of the ABCD1 gene have important implications for the etiological diagnosis of adult patients with spastic paraplegia.

Identification of brain-to-spinal circuits controlling the laterality and duration of mechanical allodynia in mice.

Mechanical allodynia (MA) represents one prevalent symptom of chronic pain. Previously we and others have identified spinal and brain circuits that transmit or modulate the initial establishment of MA. However, brain-derived descending pathways that control the laterality and duration of MA are still poorly understood. Here we report that the contralateral brain-to-spinal circuits, from Oprm1 neurons in the lateral parabrachial nucleus (lPBNOprm1), via Pdyn neurons in the dorsal medial regions of hypothalamus (dmHPdyn), to the spinal dorsal horn (SDH), act to prevent nerve injury from inducing contralateral MA and reduce the duration of bilateral MA induced by capsaicin. Ablating/silencing dmH-projecting lPBNOprm1 neurons or SDH-projecting dmHPdyn neurons, deleting Dyn peptide from dmH, or blocking spinal κ-opioid receptors all led to long-lasting bilateral MA. Conversely, activation of dmHPdyn neurons or their axonal terminals in SDH can suppress sustained bilateral MA induced by lPBN lesion.

Withdrawal of MTX in rheumatoid arthritis patients on bDMARD/tsDMARD plus methotrexate at target: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the effect of MTX withdrawal on disease activity and remission rate in patients at target after treatment with biologic DMARDs (bDMARDs)/targeted synthetic DMARDs (tsDMARDs) plus MTX. MATERIAL AND METHODS: We searched the PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials (RCTs) on MTX withdrawal in patients with RA at target after combination therapy from inception to 7 March 2022 in order to extract data, including: the change from withdrawal in DAS28 at the endpoint; proportion of low disease activity (LDA) assessed by DAS28, Simplified Disease Activity Index (SDAI) or Clinical Disease Activity Index (CDAI); proportion of remission assessed by DAS28, SDAI CDAI or ACR/EULAR Boolean remission. The Cochrane Q test and I2 test were used to assess heterogeneity, and random-effects models were used for data synthesis. This study is registered with PROSPERO (CRD42022303891). RESULTS: Six articles were included for qualitative and quantitative analysis, all of which were noninferior RCTs involving 1430 patients (734 in the withdrawal group and 696 in the continuation group). Compared with continuing combination therapy, tapering off or discontinuing MTX increased DAS28 by 0.20 (95% CI 0.09, 0.32, I2 = 0%) and decreased the percentage of patients with LDA assessed by DAS28 to <3.2 [risk ratio (RR) 0.88 (0.80, 0.97), I2 = 0%]. However, MTX withdrawal did not decrease remission rates assessed by DAS28, SDAI, CDAI or ACR/EULAR Boolean remission [RR 0.90 (0.81, 1.01), 0.93 (0.77, 1.11), 0.90 (0.74, 1.11), 0.95 (0.70, 1.29), respectively]. CONCLUSIONS: Withdrawing MTX slightly increases the RA disease activity in patients treated at target with bDMARDs/tsDMARDs plus MTX and has limited effects for patients with deep remission.

Corrigendum: Metabolomic analysis in spondyloarthritis: A systematic review.

[This corrects the article DOI: 10.3389/fmicb.2022.965709.].

Metabolomic analysis in spondyloarthritis: A systematic review.

Spondyloarthritis (SpA) is a group of rheumatic diseases that cause joint inflammation. Accumulating studies have focused on the metabolomic profiling of SpA in recent years. We conducted a systematic review to provide a collective summary of previous findings on metabolomic profiling associated with SpA. We systematically searched PubMed, Medline, Embase and Web of Science for studies on comparisons of the metabolomic analysis of SpA patients and non-SpA controls. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included articles. From 482 records identified, 31 studies were included in the analysis. A number of metabolites were differentially distributed between SpA and non-SpA cases. SpA patients showed higher levels of glucose, succinic acid, malic acid and lactate in carbohydrate metabolism, higher glycerol levels and lower fatty acid (especially unsaturated fatty acid) levels in lipid metabolism, and lower levels of tryptophan and glutamine in amino acid metabolism than healthy controls. Both conventional and biological therapy of SpA can insufficiently reverse the aberrant metabolism state toward that of the controls. However, the differences in the results of metabolic profiling between patients with SpA and other inflammatory diseases as well as among patients with several subtypes of SpA are inconsistent across studies. Studies on metabolomics have provided insights into etiological factors and biomarkers for SpA. Supplementation with the metabolites that exhibit decreased levels, such as short-chain fatty acids (SCFAs), has good treatment prospects for modulating immunity. Further studies are needed to elucidate the role of disordered metabolic molecules in the pathogenesis of SpA.

Inhibition of TNF-α and JNK Signaling Pathway Can Reduce Paclitaxel-Induced Apoptosis of Mouse Cardiomyocytes.

Paclitaxel (PTX) is a widely used chemotherapeutic drug for treating tumors. However, studies have shown that it can cause cardiac problems such as arrhythmia, myocarditis, chronic cardiomyopathy, and heart failure. Therefore, it is essential to study the mechanism behind the cardiotoxicity of PTX in tumor treatment. In this study, we initially injected PTX into mice to establish a myocardial cell apoptosis model to observe the degree of damage to mouse myocardium caused by PTX. Upon determining the levels of mouse myocardial creatine phosphokinase (CK), myokinase isoenzyme (CK-MB), aspartate transaminase (AST), and lactate dehydrogenase (LDH), we found that all of these levels showed apparent increases in mice treated with PTX. Further analyses of the TNF-α level and the expression of Jun N-terminal kinase (JNK) and Bcl-2 family-related proteins in myocardial tissue were performed. It was found that PTX increased the protein levels of TNF-α, Bax, p-JNK, and JNK in myocardial tissue but decreased the protein level of Bcl-2. After 1 month of PTX treatment in mice, we inhibited the expression of TNF-α and JNK proteins, which reduced the effect of paclitaxel on the apoptosis of mouse cardiomyocytes. The protein levels of Bax, p-JNK, and TNF-α in cardiomyocytes were reduced, while there was a relative increase in the Bcl-2 protein level. The findings suggested that inhibition of the NK signaling pathway and TNF-α can lessen the effect of PTX on mouse cardiomyocytes.

The psychological impact of COVID-19 on university students in China and Africa.

The COVID-19 pandemic is alarmingly a global health catastrophe that has created an unprecedented mental health decline especially in young adults, who have been noted to be a vulnerable population. In this study, we investigated the prevalence of depression and anxiety in university students in China and Africa during the COVID-19 pandemic, the significant factors contributing to the prevalence of anxiety and depression, the differences in factors affecting the different groups being investigated and to emphasize that psychological intervention are as important as the physical interventions during and after the pandemic. The study was conducted through online surveys, with 684 participants using Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 standardized scales. Comparing all groups combined, of the 636 participants, 361 (56.8%) had depression and 227 (35.7%) had anxiety. Chi squared tests at significance level (P<0.05) showed that country of citizenship, religion, parents' educational background, household monthly income and, having family members with COVID-19 variables were strongly associated with depression and anxiety. In contrast, age, gender, educational background, and major showed no significant association. Comparing the individual groups separately using chi square (P<0.05), the Chinese students in China group had 35.6% with depression and 13.1% with anxiety. The variable associated with both depression and anxiety was education major, with depression only was parent's educational background and with anxiety only was gender. The African students in China group had 70.3% with depression and 45.0% with anxiety. Gender was strongly associated with both depression and anxiety, and religion and having family members with COVID-19 with anxiety only. Africans in Africa had 66.0% with depression and 50.5% with anxiety. Educational background was strongly associated with depression. There was no statistically significant variable for anxiety. Chi square test showed a statistically significant difference in depression and anxiety levels with the Chinese group compared to both African groups, and no significant difference between both African groups. Our findings demonstrated that COVID-19 had a negative psychological impact on university students. Therefore, more attention should be put on youth's mental health during this pandemic.

Study on the Correlation between Chinese Medicine Syndrome and Cognitive Dysfunction in Mild Cognitive Impairment.

Objective: To investigate the correlation between Chinese medicine syndrome and cognitive dysfunction in patients with mild cognitive impairment (MCI). Methods: 121 MCI patients were included for syndrome differentiation and syndrome scoring according to the Chinese medicine syndrome classification standard of senile dementia. The cognitive function and cognitive subitems (including visual space and executive function, naming, attention, language, abstraction, delayed recall, and orientation) of patients with different Chinese medicine syndromes were scored with the Montreal Cognitive Assessment (MoCA). Correlation analysis was made on Chinese medicine syndromes and cognitive domain damage. Results: Chinese medicine syndromes from most to least were kidney deficiency and marrow reduction syndrome, turbid phlegm obstructing orifices syndrome, deficiency of heart and spleen syndrome, qi stagnation and blood stasis syndrome, and yin deficiency of heart and liver syndrome. There were no significant differences in MoCA scores among different Chinese medicine syndromes (P > 0.05).In the kidney deficiency and marrow reduction syndrome, the delayed recall score was 1.74 ± 1.23 and the difference was statistically significant when compared with deficiency of heart and spleen syndrome or the yin deficiency of heart and liver syndrome (P < 0.05). In the turbid phlegm obstructing orifices syndrome, the delayed recall score was 1.81 ± 1.33 and the difference was statistically significant when compared with the yin deficiency of heart and liver syndrome (P < 0.05). There was a significant negative correlation between the kidney deficiency and marrow reduction syndrome's Chinese medicine syndrome scores and MoCA scores (P < 0.01), and there was a negative correlation between the turbid phlegm obstructing orifices syndrome's Chinese medicine syndrome scores and MoCA scores (P < 0.05). Correlation analysis showed that the kidney deficiency and marrow reduction syndrome was significantly negatively correlated with delayed recall scores (P < 0.01), and it was also negatively correlated with visual space and executive function scores (P < 0.05). The turbid phlegm obstructing orifices syndrome was significantly negatively correlated with delayed recall scores (P < 0.01). Conclusion: The kidney deficiency and marrow reduction syndrome and the turbid phlegm obstructing orifices syndrome were the most common syndromes in MCI. Patients with kidney deficiency and marrow reduction syndrome might have obvious damage in delayed recall function and have damage in visual space and executive function. Patients with turbid phlegm obstructing orifices syndrome might have obvious damage in delayed recall function.

Sex-specific characteristics of cells expressing the cannabinoid 1 receptor in the dorsal horn of the lumbar spinal cord.

It is becoming increasingly clear that robust sex differences exist in the processing of acute and chronic pain in both rodents and humans. However, the underlying mechanism has not been well characterized. The dorsal horn of the lumbar spinal cord is the fundamental building block of ascending and descending pain pathways. It has been shown that numerous neurotransmitter and neuromodulator systems in the spinal cord, including the endocannabinoid system and its main receptor, the cannabinoid 1 receptor (CB1 R), play vital roles in processing nociceptive information. Our previous findings have shown that CB1 R mRNA is widely expressed in the brain in sex-dependent patterns. However, the sex-, lamina-, and cell-type-specific characteristics of CB1 R expression in the spinal cord have not been fully described. In this study, the CB1 R-iCre-EGFP mouse strain was generated to label and identify CB1 R-positive (CB1 RGFP ) cells. We reported no sex difference in CB1 R expression in the lumbar dorsal horn of the spinal cord, but a dynamic distribution within superficial laminae II and III in female mice between estrus and nonestrus phases. Furthermore, the cell-type-specific CB1 R expression pattern in the dorsal horn was similar in both sexes. Over 50% of CB1 RGFP cells were GABAergic neurons, and approximately 25% were glycinergic and 20-30% were glutamatergic neurons. The CB1 R-expressing cells also represented a subset of spinal projection neurons. Overall, our work indicates a highly consistent distribution pattern of CB1 RGFP cells in the dorsal horn of lumbar spinal cord in males and females.

Osteoarthritis Pain.

Joint pain is the hallmark symptom of osteoarthritis (OA) and the main reason for patients to seek medical assistance. OA pain greatly contributes to functional limitations of joints and reduced quality of life. Although several pain-relieving medications are available for OA treatment, the current intervention strategy for OA pain cannot provide satisfactory pain relief, and the chronic use of the drugs for pain management is often associated with significant side effects and toxicities. These observations suggest that the mechanisms of OA-related pain remain undefined. The current review mainly focuses on the characteristics and mechanisms of OA pain. We evaluate pathways associated with OA pain, such as nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA), calcitonin gene-related peptide (CGRP), C-C motif chemokine ligands 2 (CCL2)/chemokine receptor 2 (CCR2) and tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß), the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, and the Wnt/ß-catenin signaling pathway. In addition, animal models currently used for OA pain studies and emerging preclinical studies are discussed. Understanding the multifactorial components contributing to OA pain could provide novel insights into the development of more specific and effective drugs for OA pain management.

S100A9 blockade improves the functional recovery after spinal cord injury via mediating neutrophil infiltration.

Spinal cord injury (SCI) refers to damage to the spinal cord resulting from trauma, disease or degeneration. Controlling the inflammatory process and restoring neural homeostasis is hypothesized to prevent injury aggravation. S100 calcium-binding protein A9 (S100A9) is a pro-inflammatory alarm protein, which is expressed in and released by activated neutrophils. However, whether S100A9 could serve as an effective target for the treatment of SCI has not been reported to date. In the present study, a T10 spinal cord contusion injury model was established in Sprague-Dawley rats. S100A9 expression level was determined in the serum and injured spinal cord tissue via ELISA, reverse transcription-quantitative PCR (RT-qPCR) and western blotting. The S100A9-specific blocker, ABR-238901 (ABR), was administered during the inflammatory phase of SCI, as a form of treatment. Subsequently, the morphological structure, neuronal viability and inflammatory levels of injured spinal cord were observed by histopathology, immunohistochemistry and RT-qPCR. In the obtained results, S100A9 was found to be highly expressed in the injured spinal cord and serum in the first 3 days after SCI. However, at 28 days after surgery, ABR treatment significantly improved motor function, reduced the cavity formation and neutrophil infiltration in the lesion, which was verified via H&E staining and immunohistochemistry for myeloperoxidase. Furthermore, ABR treatment was found to effectively improve the survival and viability of neurons, as shown via Nissl staining and immunofluorescence of the synaptic plasticity markers, microtubule associated protein 2 and neurofilament 200. Moreover, S100A9 blockade effectively upregulated the mRNA expression level of the anti-inflammatory genes, IL-4 and IL-10 and downregulated the mRNA expression level of the pro-inflammatory factors, IL-1ß, IL-6 and TNF-α. In addition, S100A9 blockade notably alleviated the apoptosis level of the injured nerve cells. Therefore, the findings of the present study revealed that S100A9 may be a useful target for the treatment of SCI.