OBJECTIVE: To investigate the antidepressant effects of Xiaoyao Pill (XYP) by exploring its interactions with gut microbiota and tryptophan metabolism. METHODS: Utilizing network pharmacology, the functional substance groups, key targets, and pathways of XYP in the treatment of depression were identified. The chronic unpredictable mild stress (CUMS) protocol was implemented in male Sprague-Dawley rats to establish depression model. Thirty rats were randomly divided into 3 groups according to their body weight (10 for each): control, CUMS and XYP groups (1.8 g/kg). After 28-day interventions, behavioral phenotyping including sucrose preference test (SPT) and open field test (OFT) were performed. Biochemical validation encompassed enzyme-linked immunosorbent assay for serum cortisol, hematoxylin-eosin histopathology, and immunohistochemistry. Liquid chromatography-mass spectrometry was utilized to profile serum metabolites, while fecal samples underwent metagenomic sequencing for gut microbiota characterization. RESULTS: Network pharmacology studies predicted that key components can protect the nervous system by regulating inflammatory pathways through the blood-brain barrier. SPT and OFT showed that XYP treatment significantly ameliorated depressive-like behaviors (all P<0.05). XYP treatment also restored hippocampal neuronal density, increased serum neurotransmitter levels of neurotransmitters such as 5-hydroxytryptamine and vasoactive intestinal peptide, and while suppressing inflammatory markers such as tumor necrosis factor-alpha, interleukin-1 beta (IL-1 β), and IL-6 (all P<0.05). Metagenomics revealed significant restructuring of gut microbiota, notably the regulation of Parabacteroides distasonis (P<0.05). Non-targeted metabolomics analysis showed that the level of metabolites in the tryptophan and kynurenine pathway significantly changed (variable importance in the projection >1, P<0.05), and the change of metabolic flux was significantly correlated with behavioral improvement (P<0.05). CONCLUSIONS XYP exerts antidepressant effects by increasing neurotransmitter levels, reducing inflammatory makers and modulating Parabacteroides distasonis. Through further exploration of metabolomics, we found that XYP may play a protective role in depression by regulating tryptophan metabolism.
Animals ; Tryptophan/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/blood* ; Male ; Stress, Psychological/drug therapy* ; Behavior, Animal/drug effects* ; Rats ; Chronic Disease ; Hippocampus/drug effects*

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Cancer stands as a significant global public health challenge, and cancer screening serves as a pivotal strategy for reducing its mortality. Presently, only a limited number of cancer types have appropriate screening methods available. Traditional single-cancer screening approaches are fraught with limitations, including invasiveness, low accuracy, and poor patient compliance. Multi-cancer early detection (MCED) leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA, cell-free RNA, proteins, and metabolites in blood and other bodily fluids. This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage, showcasing immense potential for improving existing cancer screening strategies. This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED, biomarker selection and detection technologies, the criteria for cancer type selection, research design and clinical utility evaluation, as well as implementation pathways. The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED, thereby facilitating the continuous optimization of cancer screening strategies.

An implantable cardiac monitor(ICM)is a subcutaneous electronic device for recording and remotely transmitting electrocardiographic events.New-generation ICM,like the Reveal LINQ,have extended arrhythmia monitoring duration and improved diagnostic yield through miniaturization,large storage capacity,and easy implantation.They provide comprehensive monitoring data for cardiovascular disease diagnosis and treatment,optimize individualized treatment plans,and enhance patient prognosis.In recent years,research on ICM in cardiovascular fields has deepened,and their clinical application scope has expanded.They show significant advantages and unique value and are widely used in early cardiovascular disease diagnosis and prognostic management.In the future,ICM are expected to play a bigger role in boosting diagnostic and prognostic capabilities for cardiovascular disease patients,offering stronger support for early disease detection,accurate diagnosis,and effective management.

Cancer stands as a significant global public health challenge,and cancer screening serves as a pivotal strategy for reducing its mortality.Presently,only a limited number of cancer types have appropriate screening methods available.Traditional single-cancer screen-ing approaches are fraught with limitations,including invasiveness,low accuracy,and poor patient compliance.Multi-cancer early detection(MCED)leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA,cell-free RNA,proteins,and metabolites in blood and other bodily fluids.This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage,showcasing immense potential for improving existing can-cer screening strategies.This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED,biomarker selection and detection technologies,the criteria for cancer type selection,research design and clinical utility evaluation,as well as implementation path-ways.The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED,thereby facilitating the continuous optimization of cancer screening strategies.

Albendazole-glucan particles(ABZ-GPS)and abendazole(ABZ)were used to treat secondary alveolar echinococ-cosis in mice.The therapeutic effects of ABZ-GPS on alveolar echinococcosis in vivo were evaluated,and the feasibility of using glucan particles as anti-hydatid drug carriers was further verified.Mice with echinococcosis were randomly divided into an ABZ group,glucan nanoparticle(GP)group,ABZ-GPS group,and control group.After four courses of administration with a final concentration of 50 mg/mL,the therapeutic effects of ABZ-GPS were evaluated on the basis of imaging,histopathological changes,ultrastructure,and immunology.After ABZ-GPS and ABZ administration,clear liver lesion tissue necrosis and large numbers of infiltrating lymphocytes were observed.Significant differences in the average cyst wet weight(t=7.83,P＜0.05),were observed between the ABZ-GPS group and ABZ group.Imaging revealed that ABZ-GPs were targeted to liver tissue.Pa-thology and ultrastructure analyses demonstrated that the alveolar hydatid cells in the liver in the control group and GP group grew well,and the vesicles were large,filled with cystic fluid,and translucent or transparent;the cyst wall tension was high;no calcification was observed;the stratum corneum and germinal layer were clear;and more fertile capsules and different num-bers of protocephalospora were present in the liver.In the ABZ group,the capsular cavity collapsed,and showed partial necro-sis and lymphocyte infiltration.In the ABZ-GP group,the corneum and germinal layer of echinococcus vesicles were difficult to identify,and we observed bulbous necrosis,central calcification,fibrous tissue hyperplasia,inflammatory cell infiltration,coarser,shorter or absent microvilli of the germinal layer,nuclear shrinkage,dissolution or disappearance,clear expansion of cytoplasmic microtubules,and myelin-like or vacuole-like changes.Therefore,ABZ-GPs showed good targeting and killing ac-tivity in vivo in mice with secondary alveolar coccosis.

Objective:To explore the predictive value of neutrophil-to-lymphocyte ratio (NLR) and tumor necrosis factor -α (TNF-α) level on the therapeutic effect of transcatheter arterial chemoembolization (TACE) combined with microwave ablation in patients with massive liver cancer.Methods:The medical records of 106 patients with massive liver cancer who underwent TACE combined with microwave ablation treatment in the Affiliated Hospital of Weifang Medical University from February 2020 to February 2023 were retrospectively analyzed. The efficacy was evaluated 6 weeks after surgery, and the patients were divided into remission group and non-remission group according to the therapeutic effect. The levels of NLR and TNF-α in the two groups were detected before surgery, 3 days after surgery and 7 days after surgery. Point two column correlation was used to analyze the relationship between the levels of NLR and TNF-α in different time periods and the therapeutic effect of TACE combined with microwave ablation in patients with massive liver cancer. The receiver operator characteristic (ROC) curve was drawn to analyze the predictive value of NLR and TNF-α levels in different time periods for the therapeutic effect of TACE combined with microwave ablation in patients with massive liver cancer.Results:Six weeks after surgery, out of 106 patients with massive liver cancer, 13 achieved complete remission, 48 achieved partial remission, 20 experienced disease progression, and 25 remained stable. The overall remission rate was 57.55% (61/106). Before surgery, the levels of NLR [ (2.26±0.13) vs. (2.43±0.12), t=6.87, P<0.001] and TNF-α [ (36.20±4.38) pg/ml vs. (42.74±5.74) pg/ml, t=6.66, P<0.001] in the remission group ( n=61) were lower than those in the non-remission group ( n=45), with statistically significant differences. At 3 days after surgery, there were no statistically significant difference in the levels of NLR [ (6.16±3.22) vs. (6.22±3.30), t=0.09, P=0.925] or TNF-α [ (48.84±7.22) pg/ml vs. (49.13±7.34) pg/ml, t=0.20, P=0.840] between the remission group and the non-remission group. At 7 days after surgery, the levels of NLR [ (2.60±0.18) vs. (2.82±0.26), t=5.15, P<0.001] and TNF-α [ (38.20±6.30) pg/ml vs. (45.57±5.79) pg/ml, t=6.16, P<0.001] in the remission group were lower than those in the non-remission group, with statistically significant differences. There were statistically significant differences in NLR and TNF-α levels before surgery, 3 days and 7 days after surgery between the remission group and the non-remission group ( F=82.43, P<0.001; F=54.45, P<0.001; F=76.23, P<0.001; F=15.61, P<0.001). Further pair-to-pair comparison showed that the levels of NLR and TNF-α were higher in both groups 3 and 7 days after surgery than before surgery, but the levels of NLR and TNF-α were lower in both groups 7 days after surgery than 3 days after surgery, with statistically significant differences (all P<0.005). Point two column correlation analysis showed that NLR level, TNF-α level and the efficacy of TACE combined with microwave ablation in patients with massive liver cancer were significantly positively correlated before and 7 days after surgery ( r=0.42, P<0.001; r=0.49, P<0.001; r=0.43, P<0.001; r=0.46, P<0.001). ROC curve showed that the area under the curve (AUC) of NLR and TNF-α alone in predicting the efficacy of TACE combined with microwave ablation in patients with massive liver cancer before and 7 days after surgery was 0.750 (95% CI: 0.656-0.844), 0.788 (95% CI: 0.699-0.877), 0.751 (95% CI: 0.652-0.850), 0.788 (95% CI: 0.700-0.876), respectively. The AUC of combined prediction of NLR and TNF-α before and 7 days after surgery were 0.818 (95% CI: 0.736-0.900) and 0.813 (95% CI: 0.730-0.897), respectively. There were no statistically significant differences in the AUC values of NLR and TNF-α alone or in combination for predicting the therapeutic effect of TACE combined with microwave ablation in patients with massive liver cancer before and 7 days after surgery (all P>0.05) . Conclusions:The levels of NLR and TNF-α before and 7 days after surgery are related to the effect of TACE combined with microwave ablation in patients with massive liver cancer, and the combination of NLR and TNF-α levels before and 7 days after surgery has certain value in predicting the effect of TACE combined with microwave ablation in patients with massive liver cancer.

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

Objective:To evaluate the effectiveness and safety of zoledronic acid in patients with Paget′s disease of bone based on clinical data from a single medical center.Methods:This retrospective study included 24 patients diagnosed with Paget′s disease of bone and treated with zoledronic acid at Peking Union Medical College Hospital between January 2009 and June 2020. Demographic data, clinical symptoms, treatment efficacy, and safety outcomes were collected. The primary efficacy measure was serum alkaline phosphatase(ALP) levels. Treatment was considered effective if ALP levels returned to normal or decreased by more than 75% from baseline in the difference between the ALP level and its normal median value.Results:Among the 24 patients with Paget′s bone disease, the most commonly affected site was the skull(in 17 cases). All patients received a single 5 mg intravenous infusion of zoledronic acid. Serum ALP levels significantly decreased after treatment. Among the 15 patients who completed at least 3 months of follow-up, all achieved treatment success. The median time for serum ALP levels to reach the target was 13.1(9.4, 26.1) weeks. In 12 patients, ALP levels normalized within a medium of 16.9(11.5, 37.3) weeks, and remained stable over a medium follow-up of 4.56(2.42, 5.71) years. The most common side effects were hypocalcemia(21 cases, 87.5%) and flu-like symptoms(17 cases, 70.8%). Seven patients had severe hypocalcemia(serum calcium<1.75 mmol/L), and they had higher baseline levels of ALP, calcium, and phosphorus compared to those with mild hypocalcemia.Conclusions:Zoledronic acid 5 mg intravenous infusion effectively controlled disease activity in patients with Paget′s disease of bone. Generally, Most patients achieved treatment goals within 3-4 months, with sustained remission for a median of 4 years. Hypocalcemia was the most frequent side effect, underscoring the importance of timely calcium and vitamin D supplementation.