Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

BACKGROUND:Traditional surgery for lumbar disc herniation involves extensive excision of tissue surrounding the nerve for decompression and removal of protruding lumbar intervertebral discs,which poses various risks and complications such as nerve damage causing paralysis,lumbar instability,herniation recurrence,intervertebral space infection,and adjacent vertebral diseases. OBJECTIVE:To propose the symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous technique for lumbar spine symmetrically decompression,showing the induced resorption of herniated nucleus pulpous phenomenon and early clinical efficacy,and then analyze its decompression mechanism. METHODS:214 patients with lumbar disc herniation at Department of Orthopedics,First Affiliated Hospital of Zhengzhou University from March 2021 to May 2023 were enrolled in this study.Among them,81 patients received conservative treatment as the control group,and 133 patients received symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous treatment as the trial group.Before surgery,immediately after surgery(7-14 days),and early after surgery(over 1 year),MRI images were used to measure the volume changes of lumbar disc herniation.CT images were used to measure the posterior displacement distance of the lumbar spinous process ligament complex,as well as the width and height of the lateral recess.Japanese Orthopaedic Association scores were used to evaluate the patient's neurological function recovery. RESULTS AND CONCLUSION:(1)Control group:81 patients with lumbar disc herniation were treated conservatively,with a total of 171 herniated lumbar discs.The average follow-up time was(22.7±23.1)months.The first and second MRI measurements of 171 herniated lumbar discs showed herniated lumbar disc volumes of(551.6±257.9)mm3 and(792.2±330.4)mm3,respectively,with an average volume increase rate of(53.2±44.4)%,showing statistically significant differences(P<0.001).Out of 171 herniated lumbar discs,4 experienced natural shrinkage,with an absorption ratio of 2.3%(4/171)and an absorption rate of(24.5±9.9)%.(2)Trial group:133 patients with lumbar disc herniation had a total of 285 herniated lumbar discs.(1)Immediately after surgery:All patients were followed up immediately after surgery.229 out of 285 herniated lumbar discs experienced retraction,with an absorption ratio of 80.3%(229/285)and an average absorption rate of(21.5±20.9)%,with significant and complete absorption accounting for 6.5%.There were a total of 70 herniated lumbar discs in the upper lumbar spine,with an absorption ratio of 85.7%(60/70),an average absorption rate of(23.1±19.5)%,and a maximum absorption rate of 86.6%.There were 215 herniated lumbar discs in the lower lumbar spine,with an absorption ratio of 78.6%(169/215),an average absorption rate of(21.0±21.3)%,and a maximum absorption rate of 83.2%.Significant and complete absorption of the upper and lower lumbar vertebrae accounted for 5.7%and 6.5%,respectively,with no statistically significant difference(P>0.05).The average distance of posterior displacement of the spinous process ligament complex immediately after surgery was(5.2±2.8)mm.There were no significant differences in the width and height of the left and right lateral recess before and immediately after surgery(P>0.05).The Japanese Orthopaedic Association score immediately after surgery increased from(10.1±3.4)before surgery to(17.0±4.8),and the immediate effective rate after surgery reached 95.6%.(2)Early postoperative period:Among them,46 patients completed the early postoperative follow-up.There were 101 herniated lumbar discs,with an absorption ratio of 94%(95/101)and an average absorption rate of(36.9±23.7)%.Significant and complete absorption accounted for 30.6%,with a maximum absorption rate of 100%.Out of 101 herniated lumbar discs,3 remained unchanged in volume,with a volume invariance rate of 2.97%(3/101).Out of 101 herniated lumbar discs,3 had an increased volume of herniated lumbar discs,with an increase ratio of 2.97%(3/101)and an increase rate of(18.5±18.4)%.The Japanese Orthopaedic Association score increased from preoperative(9.3±5.1)to(23.5±4.0),with an excellent and good rate of 93.4%.(3)The early postoperative lumbar disc herniation absorption ratios of the control group and trial group were 2.3%and 85.9%,respectively,with statistically significant differences(P<0.001).(4)Complications:There were two cases of incision exudation and delayed healing in the trial group.After conservative treatment such as dressing change,no nerve injury or death occurred in the incision healing,and no cases underwent a second surgery.(5)It is concluded that symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous is a new method for treating lumbar disc herniation that can avoid extensive excision of the"ring"nerve and achieve satisfactory early clinical efficacy.It does not damage the lumbar facet joints or alter the basic anatomical structure of the lateral recess,fully preserves the herniated lumbar discs,and can induce significant or even complete induced resorption of herniated nucleus pulpous.Symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous provides a new basis and method for the clinical treatment of lumbar disc herniation.

Objective: Adolescent depression is a highly prevalent and disabling mental disorder with unclear pathophysiology and unfavorable treatment outcomes. Recent efforts have been focusing on searching for biomarkers as specific indicators of adolescent depression. We performed a systematic literature review and meta-analysis, specifically including studies with healthy control groups as an inclusion criterion. This approach helps to avoid confounding factors and provides more accurate results regarding the inflammatory and immune biomarkers associated with adolescent depression. Methods: Three electronic databases were searched for studies comparing the means and changes in the biomarkers between depressed adolescent patients and healthy controls published in English until February 2024. Two authors independently performed the screening, quality assessment, and data extraction of the studies. A meta-analysis was conducted on outcomes reported by two or more studies using a random-effects model and presented Forrest plots and test statistics (I2) for heterogeneity analysis. Results: Nine studies were included in the review, including seven case-control studies and two cross-sectional studies. These studies included 24 target biomarkers, 13 of which were quantified in 2 or more studies. Compared to the healthy controls, the depressed adolescents had significantly higher values in ten indicators. Additionally, the depressed adolescents had lower procalcitonin levels than the healthy controls. The two groups showed no significant differences in the remaining 13 biomarkers. Conclusion Our findings offer fresh insights into the pathophysiology of inflammatory and immune aspects of adolescent depression and provide helpful guidance in developing targeted and effective intervention and prevention strategies to address adolescent depression.

Objective: Adolescent depression is a highly prevalent and disabling mental disorder with unclear pathophysiology and unfavorable treatment outcomes. Recent efforts have been focusing on searching for biomarkers as specific indicators of adolescent depression. We performed a systematic literature review and meta-analysis, specifically including studies with healthy control groups as an inclusion criterion. This approach helps to avoid confounding factors and provides more accurate results regarding the inflammatory and immune biomarkers associated with adolescent depression. Methods: Three electronic databases were searched for studies comparing the means and changes in the biomarkers between depressed adolescent patients and healthy controls published in English until February 2024. Two authors independently performed the screening, quality assessment, and data extraction of the studies. A meta-analysis was conducted on outcomes reported by two or more studies using a random-effects model and presented Forrest plots and test statistics (I2) for heterogeneity analysis. Results: Nine studies were included in the review, including seven case-control studies and two cross-sectional studies. These studies included 24 target biomarkers, 13 of which were quantified in 2 or more studies. Compared to the healthy controls, the depressed adolescents had significantly higher values in ten indicators. Additionally, the depressed adolescents had lower procalcitonin levels than the healthy controls. The two groups showed no significant differences in the remaining 13 biomarkers. Conclusion Our findings offer fresh insights into the pathophysiology of inflammatory and immune aspects of adolescent depression and provide helpful guidance in developing targeted and effective intervention and prevention strategies to address adolescent depression.

Objective: Adolescent depression is a highly prevalent and disabling mental disorder with unclear pathophysiology and unfavorable treatment outcomes. Recent efforts have been focusing on searching for biomarkers as specific indicators of adolescent depression. We performed a systematic literature review and meta-analysis, specifically including studies with healthy control groups as an inclusion criterion. This approach helps to avoid confounding factors and provides more accurate results regarding the inflammatory and immune biomarkers associated with adolescent depression. Methods: Three electronic databases were searched for studies comparing the means and changes in the biomarkers between depressed adolescent patients and healthy controls published in English until February 2024. Two authors independently performed the screening, quality assessment, and data extraction of the studies. A meta-analysis was conducted on outcomes reported by two or more studies using a random-effects model and presented Forrest plots and test statistics (I2) for heterogeneity analysis. Results: Nine studies were included in the review, including seven case-control studies and two cross-sectional studies. These studies included 24 target biomarkers, 13 of which were quantified in 2 or more studies. Compared to the healthy controls, the depressed adolescents had significantly higher values in ten indicators. Additionally, the depressed adolescents had lower procalcitonin levels than the healthy controls. The two groups showed no significant differences in the remaining 13 biomarkers. Conclusion Our findings offer fresh insights into the pathophysiology of inflammatory and immune aspects of adolescent depression and provide helpful guidance in developing targeted and effective intervention and prevention strategies to address adolescent depression.

Objective: Adolescent depression is a highly prevalent and disabling mental disorder with unclear pathophysiology and unfavorable treatment outcomes. Recent efforts have been focusing on searching for biomarkers as specific indicators of adolescent depression. We performed a systematic literature review and meta-analysis, specifically including studies with healthy control groups as an inclusion criterion. This approach helps to avoid confounding factors and provides more accurate results regarding the inflammatory and immune biomarkers associated with adolescent depression. Methods: Three electronic databases were searched for studies comparing the means and changes in the biomarkers between depressed adolescent patients and healthy controls published in English until February 2024. Two authors independently performed the screening, quality assessment, and data extraction of the studies. A meta-analysis was conducted on outcomes reported by two or more studies using a random-effects model and presented Forrest plots and test statistics (I2) for heterogeneity analysis. Results: Nine studies were included in the review, including seven case-control studies and two cross-sectional studies. These studies included 24 target biomarkers, 13 of which were quantified in 2 or more studies. Compared to the healthy controls, the depressed adolescents had significantly higher values in ten indicators. Additionally, the depressed adolescents had lower procalcitonin levels than the healthy controls. The two groups showed no significant differences in the remaining 13 biomarkers. Conclusion Our findings offer fresh insights into the pathophysiology of inflammatory and immune aspects of adolescent depression and provide helpful guidance in developing targeted and effective intervention and prevention strategies to address adolescent depression.

The relationship between gut microbiota and depressive disorder has become a research focus in recent years. Within the microbiota-gut-brain axis, the gut microbiota influences the onset and progression of depressive disorder primarily through the tryptophan metabolic pathway. Tryptophan, an essential amino acid in humans, is subject to dual regulation by intestinal microorganisms, which modulate its metabolic balance via inflammatory stimulation and microbial metabolite production. In depression, excessive activation of the kynurenine branch of tryptophan metabolism leads to the accumulation of proinflammatory and neurotoxic metabolites, thereby exacerbating neuroinflammation in the brain. Intervention studies indicate that the antidepressant-like effects of probiotics and traditional Chinese medicine are associated with remodeling of the gut microbiota, restoration of tryptophan metabolic balance, and alleviation of neuroinflammation. Furthermore, targeted inhibition of kynurenine 3-monooxygenase can mitigate neuroinflammation by regulating microglial activity, thus improving depressive-like behaviors. In summary, the metabolite-inflammation axis represents a central node in the interaction regulation between tryptophan metabolism and the microbiota-gut-brain axis. This provides a theoretical foundation for developing novel therapeutic strategies targeting depression through modulation of gut microbiota-mediated tryptophan metabolism.
Tryptophan/metabolism* ; Gastrointestinal Microbiome/physiology* ; Humans ; Depressive Disorder/microbiology* ; Probiotics/therapeutic use* ; Brain/metabolism* ; Kynurenine/metabolism* ; Metabolic Networks and Pathways ; Animals ; Medicine, Chinese Traditional

Objective:To analyze the efficacy, influencing factors, and risk warning of multi-plane low-temperature plasma radiofrequency ablation（MLT-RFA） in the treatment of obstructive sleep apnea hypopnea syndrome（OSAHS）. Methods:A total of 118 OSAHS patients admitted from October 2022 to June 2024 were selected as the research subjects. They were divided into mild group（n=46）, moderate group（n=52）, and severe group（n=20） according to the severity of their condition. MLT-RFA treatment was used for all patients. After surgery, the results of polysomnography（PSG） and the changes in the Calier Sleep Apnea Quality of Life Index（SAQLI） were observed before and after treatment. The incidence of complications after treatment was recorded, and the clinical efficacy of the patients was evaluated. At the same time, they were divided into a treatment effective group（n=106） and an ineffective group（n=12） according to their effects. The general clinical data of the two groups were compared, and binary logistics regression analysis was conducted to identify independent factors that affect treatment efficacy and construct a model. ROC curve analysis was used to evaluate the diagnostic efficacy of the model. Results:The treatment effectiveness rate of the mild group was 93.48%, the moderate group was 90.38%, and the severe group was 80.00%. There was no statistically significant difference in the treatment effectiveness rate among the three groups（P>0.05）. The AHI of the mild group, moderate group, and severe group increased sequentially, while the LSaO2and SAQLI scores decreased sequentially. After treatment, the AHI of all three groups decreased compared to before treatment, while the LSaO2and SAQLI scores increased compared to before treatment, and the differences were statistically significant（P<0.05）. The pre-treatment AHI of the effective group was lower than that of the ineffective group, and the pre-treatment LSaO2and SAQLI were higher than those of the ineffective group, with statistically significant differences（P<0.05）. Pre-treatment LSaO2and pre-treatment SAQLI are independent factors affecting the efficacy of MLT-RFA（P<0.05）. The AUC of pre-treatment LSaO2, pre-treatment SAQLI, and combined prediction were 0.907, 0.763, and 0.947, respectively, with sensitivities of 0.896, 0.840, and 0.917, and specificities of 0.833, 0.667, and 0.887, respectively. Conclusion:MLT-RFA has a significant effect on the treatment of OSAHS, and the AHI, LSaO2, and SAQLI of patients before treatment can predict the treatment effect, with LSaO2 and SAQLI being independent influencing factors. The combinerd prediction model exhibits high diagnostic efficiency, sensitivity, and specificity.
Radiofrequency Ablation/methods* ; Plasma Gases ; Sleep Apnea, Obstructive/surgery* ; Polysomnography ; Postoperative Complications/epidemiology* ; Quality of Life ; Severity of Illness Index ; Treatment Outcome ; Humans

Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.