This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Objective To explore the pathogenic mechanisms of Legionella pneumophila(L.pneumophila)infection inhibiting the fusion of endosome-lysosome fusion in mouse macrophages.Methods Twelve C57 mice were randomly divided into control group and L.pneumophila infection group(n=6 each).After anesthesia,an equal volume of physiological saline or L.pneumophila solution was administered nasally.Body weight changes were monitored for 3 consecutive days,and the lungs were extracted to assess injury.Hematoxylin and eosin(HE)staining and immunohistochemical staining were performed to observe the pathological characteristics of lung tissue in both groups.Transcriptome sequencing was utilized to analyze differentially expressed genes(DEGs)and associated signaling pathways in lung tissues.Mouse bone marrow macrophages(BMDMs)were isolated and co-cultured with L.pneumophila,with infection status confirmed by immunofluorescence staining.Transcriptome sequencing was employed to analyze DEGs and enriched related signaling pathways before and after infection.Core genes involved in the post-infection signaling pathway were identified,and the consistency of their mRNA expression levels in vivo and in vitro was verified using RT-qPCR.The expression of relevant proteins was detected by Western Blotting,and bacterial proliferation assays were conducted to evaluate the intracellular replication of L.pneumophila.Results Compared with control group,the body weight of mice in L.pneumophila infection group significantly decreased(P<0.001)on the second and third day post-infection.Edema and red hepatoid degeneration were observed in both left and right lung tissues,with lesion areas spreading from the hilum to the lung periphery.HE staining revealed increased inflammatory cell infiltration in the alveolar spaces,thickening of alveolar septa and increased fibrin exudation in L.pneumophila infection group.Immunohistochemistry results showed a significant increase in myeloperoxidase(MPO)activity in the lung tissue infected mice(P<0.001).Transcriptome sequencing identified 2550 DEGs,with 1444 up-regulated genes and 1106 down-regulated genes.KEGG enrichment analysis indicated that these DEGs were mainly involved in pathways related to tumor necrosis factor,rheumatoid arthritis,Rap1,PI3K-Ak,and phagosome pathways.Immunofluorescence results showed in vitro proliferation of L.pneumophila within mouse BMDMs.Transcriptome sequencing identified 2550 DEGs,including 1677 up-regulated genes and 873 down-regulated genes.KEGG enrichment analysis showed that enrichment in pathway related to transcription dysregulation in cancer,PI3K-Akt and phagosome pathways.Thirteen core genes,including tubulin β1(Tubb1),were identified from the overlap between mouse lung tissue and BMDMs.RT-qPCR results demonstrated a significant decrease in Tubb1 expression in both lung tissue and BMDMs infected with L.pneumophila(P<0.001).Western Blotting results revealed significant decreases in Rab7,Tubb1,and LAMP2 protein expression(P<0.05),and increases in iNOS and MPO expression(P<0.05).Intracellular proliferation experiments indicated that L.pneumophila gradually increased within BMDMs over time.Conclusion The potential mechanism of L.pneumophila infection in mouse macrophages involves the down-regulation of Rab7/Tubb1/LAMP2 which inhibits the endosome-lysosome fusion.

Aim To investigate the effects of breast cancer-related depression model on microglial activa-tion and neuronal function via the NLRP3-COX-2 sig-naling pathway.Methods In the cell experiment,BV2 and HT22 cells were co-cultured to observe the polarization of BV2 cells and the injury of HT22 cells.In the animal experiment,behavioral experiments were used to evaluate the depressive behaviors of mice.HE staining and tumor weight were used to evaluate the changes of axillary tumors.ELISA was used to detect the contents of CA153,CA125,CEA,as well as the changes in the contents of 5-HT,DA and others in the serum and hippocampus.RT-qPCR and immunohisto-chemistry were used to detect the mRNA and protein expression of IL-1 β,IL-18 and other indicators,re-spectively.Immunofluorescence was used to detect CD1 1b and Iba-1.Nissl staining and transmission elec-tron microscopy were used to observe the hippocampal neurons.Results The results of cell experiments showed that compared with the model group,the pro-tein contents and mRNA expression levels of NLRP3,COX-2,and IL-1 β in the NLRP3 knockdown group were all decreased.The results of animal experiments showed that compared with the model group,the be-havioral performance of the experimental group was im-proved,and the mRNA and protein expression levels of IL-1 β,IL-18,and NLRP3 were decreased.Conclu-sion BCRD may mediate the polarization of microglia and the injury of hippocampal neurons through the NL-RP3-COX-2 signaling pathway.

Aim To investigate the effects of breast cancer-related depression model on microglial activa-tion and neuronal function via the NLRP3-COX-2 sig-naling pathway.Methods In the cell experiment,BV2 and HT22 cells were co-cultured to observe the polarization of BV2 cells and the injury of HT22 cells.In the animal experiment,behavioral experiments were used to evaluate the depressive behaviors of mice.HE staining and tumor weight were used to evaluate the changes of axillary tumors.ELISA was used to detect the contents of CA153,CA125,CEA,as well as the changes in the contents of 5-HT,DA and others in the serum and hippocampus.RT-qPCR and immunohisto-chemistry were used to detect the mRNA and protein expression of IL-1 β,IL-18 and other indicators,re-spectively.Immunofluorescence was used to detect CD1 1b and Iba-1.Nissl staining and transmission elec-tron microscopy were used to observe the hippocampal neurons.Results The results of cell experiments showed that compared with the model group,the pro-tein contents and mRNA expression levels of NLRP3,COX-2,and IL-1 β in the NLRP3 knockdown group were all decreased.The results of animal experiments showed that compared with the model group,the be-havioral performance of the experimental group was im-proved,and the mRNA and protein expression levels of IL-1 β,IL-18,and NLRP3 were decreased.Conclu-sion BCRD may mediate the polarization of microglia and the injury of hippocampal neurons through the NL-RP3-COX-2 signaling pathway.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Aberration of the right coronary artery from the left anterior descending is a very rare congenital anomaly.The anomalous the right coronary artery,as a branch of the septal branch,has not been reported clinically.This article reports such rare case.A 52-year-old female was admitted due to"sudden chest pain and confusion for 4 hours".The ECG showed that the ST-segment of leads(V1-V4,V3R,V4R and V5R)were elevated about 0.1-0.3 mVThe blood pressure was 63/53 mmHg.She was diagnosed as cardiogenic shock second to acute anterior and right ventricular ST-segment elevation myocardial infarction.Emergency coronary angiography was performed after intra-aortic ballon pump was implanted to assist circulation.During the treatment of the culprit vessel,it was accidentally found that the right coronary artery,as a branch vessel,originated from the ostium of the second septal branch of the anterior descending artery.