OBJECTIVES: To investigate the therapeutic mechanism of Huoxue Shufeng Granules (HXSFG) for alleviating central sensitization in a mouse model of chronic migraine (CM). METHODS: We analyzed the main chemical components of HXSFG through literature review and explored their pharmacological mechanisms by bioinformatics analyses. In a male C57BL/6J mouse model of CM established by intraperitoneal injections of nitroglycerin (10 mg/kg) every other day (5 injections), the effects of gavage with low, and high doses of HXSFG or intraperitoneal injections of topiramate for ameliorating central sensitization were evaluated using Von Frey test and a hot plate apparatus; the changes in expressions of inflammatory factors, the proteins in the TLR4/NF‑κB signaling pathway, and activation of c-Fos and CGRP were detected using RT-qPCR, Western blotting and immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that the main active components in HXSFG for alleviating CM included formononetin, paeoniflorin, quercetin, and tanshinone. Gene Ontology (GO) enrichment analysis identified 492 GO entries, comprising 366 biological processes, 46 cellular components, and 80 molecular functions. KEGG pathway enrichment analysis indicated that the Toll-like receptor and NF‑κB signaling pathways were crucial in mediating the therapeutic effects of HXSFG on CM. In the mouse models of CM, both topiramate and HXSFG treatments alleviated the symptoms of central sensitization, evidenced by improved mechanical and thermal pain thresholds in the mice. HXSFG significantly reduced the expression of c-Fos and CGRP, improved inflammatory markers, and downregulated the expressions of TLR4, p-NF‑κB, IL-1β, and TNF‑α proteins in the mouse models. CONCLUSIONS HXSFG effectively alleviates central sensitization in CM mice by modulating the inflammatory pathways and inhibiting the TLR4/ NF-κB signaling pathway, suggesting its potential as a therapeutic option for CM.
Animals ; Toll-Like Receptor 4/metabolism* ; NF-kappa B/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Male ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Migraine Disorders/metabolism* ; Disease Models, Animal ; Inflammation

OBJECTIVES: To investigate the mechanisms of Modified Chaihu Guizhi Decoction (MCGD) for ameliorating anxiety- and depression-like behaviors in a mouse model of chronic unpredictable mild stress (CUMS). METHODS: The main chemical constituents of MCGD were identified through literature review, and network pharmacology analysis was performed to predict the potential pharmacological mechanisms of MCGD. For in vivo validation, male C57BL/6J mice were randomized into control group, CUMS model group, fluoxetine (FLX) treatment group, and low- and high-dose MCGD treatment groups (n=15), and in all but the control group, CUMS models were established by daily exposure to two randomized stressors for 28 consecutive days. Starting from 3 days prior to modeling, MCGD and fluoxetine treatments were administered daily via gavage and intraperitoneal injection, respectively. Depression- and anxiety-like behaviors of the mice were assessed using sucrose preference test, forced swim test, open field test and elevated plus maze test. The changes in mRNA expressions of the clock genes and inflammatory markers and expressions of the JAK2/STAT3 signaling proteins were detected using RT-qPCR and Western blotting, and immunofluorescence staining was used to detect microglia activation in the mice. RESULTS: The key active compounds in MCGD identified by network pharmacology analysis included quercetin, acacetin, formononetin, nobiletin, and baicalein. GO analysis identified 607 enriched pathways, and KEGG pathway enrichment revealed significant involvement of the JAK2/STAT3 and NF-κB signaling pathways. In the mouse models of CUMS, treatment with both fluoxetine and MCGD significantly alleviated anxiety- and depression-like behaviors. MCGD treatment significantly reduced Iba1 expression, improved the inflammatory markers, reversed the decrease in clock gene circadian rhythm amplitude, and obviously downregulated the expressions of JAK2, p-STAT3, p-NF-κB, IL-1β, and IL-6 proteins. CONCLUSIONS MCGD effectively alleviates anxiety- and depression-like behaviors in CUMS mice by modulating the inflammatory pathways and inhibiting the JAK2/STAT3 signaling pathway.
Animals ; Janus Kinase 2/metabolism* ; STAT3 Transcription Factor/metabolism* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; Mice, Inbred C57BL ; Anxiety/drug therapy* ; Stress, Psychological ; Disease Models, Animal

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

OBJECTIVE: To compare the clinical efficacy of acupuncture with yin-yang regulation method versus local acupuncture in treating chronic low back pain (CLBP) in elderly patients with lumbar disc herniation (LDH), and to evaluate the changes in the multifidus muscle before and after treatment using musculoskeletal ultrasound. METHODS: A total of 128 elderly patients with CLBP due to LDH were randomly assigned to an observation group (64 cases, 2 cases dropped out) and a control group (64 cases, 2 cases dropped out). The control group received local acupuncture at bilateral L₃-L₅ Jiaji points (EX-B2), Shenshu (BL23), Dachangshu (BL25), Weizhong (BL40), Yaoyangguan (GV3), and ashi points. The observation group received acupuncture with yin-yang regulation method, which included an abdominal protocol with Baihui (GV20), Zhongwan (CV12), Qihai (CV6), Guanyuan (CV4), bilateral Tianshu (ST25), and Dahe (KI12), etc., and a lumbar protocol with Baihui (GV20), Dazhui (GV14), Jizhong (GV6), Yaoyangguan (GV3), and ashi points, etc., alternated bilaterally. Both groups were treated once every other day, three times per week, for a total of 12 sessions. The visual analogue scale (VAS) score, Oswestry disability index (ODI) score, and the indexs of musculoskeletal ultrasound multifidus muscle (resting and functional thickness and Young's modulus values) were observed before and after treatment, and the clinical efficacy was evaluated in the two groups. RESULTS: After 1 and 4 weeks of treatment, both groups showed lower VAS scores compared to baseline (P<0.05), the VAS scores in the observation group were lower than those in the control group (P<0.001). ODI scores in both groups were decreased after 1 and 4 weeks of treatment compared to baseline (P<0.05), with a further reduction at 4 weeks of treatment compared to 1 week of treatment (P<0.05); the observation group showed lower ODI score than the control group after 1 week of treatment (P<0.001). After treatment, both groups demonstrated increased resting and functional multifidus muscle thickness bilaterally compared to baseline (P<0.01), with an increased right-side thickness change rate (P<0.01), though no significant difference was observed between groups (P>0.05). Compared to baseline, after treatment, the observation group exhibited decreased Young's modulus values for bilateral resting and functional multifidus muscle (P<0.01), while the control group showed reductions only in bilateral resting and right-side functional Young's modulus values (P<0.01). After treatment, the bilateral functional Young's modulus values in the observation group were lower than that in the control group (P<0.05), and the bilateral resting and functional changes in Young's modulus values were greater in the observation group than those in the control group (P<0.01). The overall effective rate was 93.5% (58/62) in the observation group, which was higher than 79.0% (49/62) in the control group (P<0.05). CONCLUSION Acupuncture with yin-yang regulation method effectively alleviates pain, improves functional disability, increases multifidus muscle thickness, and reduces Young's modulus values in elderly patients with CLBP due to LDH, which has superior therapeutic effect compared to local acupuncture.
Humans ; Low Back Pain/physiopathology* ; Male ; Acupuncture Therapy ; Female ; Aged ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Yin-Yang ; Lumbar Vertebrae ; Acupuncture Points ; Treatment Outcome

Central serous chorioretinopathy(CSC), the first described pachychoroid disease, is characterized by visual distortions and loss of vision, which are commonly seen in middle-aged male. Research has demonstrated that ocular blood flow in CSC is in a state of overload, characterized by the dilation of vortex vein ampullae and choroidal vasculature. The obstruction of venous outflow is linked to scleral thickness, while the choriocapillaris exhibits perfusion deficits due to compression from the engorged vascular layer. Over time, vascular remodeling occurs, with venous anastomoses forming to create alternative drainage pathways and mitigate blood stasis. These abnormalities in vortex vein dynamics and choroidal circulation play a critical role in elucidating the underlying pathogenesis and clinical manifestations of CSC. This review highlights the alterations in vortex vein and choroidal vasculature in CSC, hoping to understand how the changes of blood flow affect the course of CSC and their correlation with treatment response. By evaluating blood flow dynamics, we aim to determine the disease stage more accurately, optimize therapeutic strategies, and ultimately enhance patient outcomes.

Objective To construct and validate a risk prediction model for in-hospital death af-ter successful resuscitation in patients with cardiac arrest.Methods A retrospective study was con-ducted on 295 patients with cardiac arrest who successfully restored spontaneous circulation after car-diopulmonary resuscitation and were further treated in hospital.The patients were divided into training and validation sets using K-fold cross-validation and then grouped and compared based on whether in-hospital death occurred.A binary Logistic regression analysis was used to screen risk prediction fac-tors,and a nomogram prediction model was constructed.The model performance was evaluated and validated in the training and validation sets,respectively.Results The results of the multivariate Logistic regression analysis showed that hospitalization duration(OR=1.180;95％CI,1.080 to 1.280;P＜0.001),norepinephrine dose(OR=0.980;95％CI,0.970 to 0.990;P=0.002),ini-tial respiratory rate after resuscitation(OR=1.090;95％CI,1.030 to 1.150;P=0.004),and sinus rhythm recovery after resuscitation(OR=4.280;95％CI,1.670 to 10.980;P=0.003)were inde-pendent influencing factors for in-hospital death.A nomogram model was constructed based on these in-dependent influencing factors,and it was verified that the model had good discrimination,calibration,applicability,and rationality.Conclusion The influencing factors for in-hospital death after successful resuscitation in patients with cardiac arrest include hospitalization duration,norepinephrine dose,initial respiratory rate after resuscitation,and sinus rhythm recovery after resuscitation.The nomo-gram model constructed based on these factors can provide a reference for clinical decision-making.

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

As an important setting for the administration of vaccinations, the reasonable setting up and standardized management of vaccination clinics will enhance immunization service quality, public satisfaction, and improve the vaccination rate to protect people′s health. In recent years, various provinces in China are continuously promoting the standardized construction and management of vaccination clinics. However, the level of standardization management remains unbalanced, and the capacity of vaccination services needs to be further improved. This paper reviews the standardized management process of vaccination clinics, summarizes the practice and achievements in various regions, and analyzes the challenges and issues during these processes, to provide reference for improving the standardized management level of vaccination clinics in the future.