BACKGROUND AND AIMS:Acute liver failure (ALF) is a life-threatening disease with a high mortality rate and limited treatment options. Neutrophils rapidly infiltrate the injured liver, yet their functional heterogeneity and regulatory mechanisms remain poorly understood. We aimed to identify pathogenic neutrophil subsets in ALF and identify potential therapeutic targets. APPROACH AND RESULTS:Single-cell RNA sequencing of liver tissues from murine ALF revealed the expansion of Ifit1 + neutrophil subset, which was conserved across diverse etiologies. This subset exacerbates liver injury by amplifying inflammatory responses and inducing hepatocyte apoptosis. FGL2 was identified as the principal effector secreted by this subset. Mechanistically, IRF7 acted as an upstream transcriptional regulator of Ifit1 + neutrophil differentiation. Neutrophil-specific Irf7 deficiency reduced Ifit1 + neutrophil expansion, diminished FGL2 production, mitigated liver injury, and improved survival. Liver neutrophil-targeted lipid nanoparticles delivering the IRF7 small-molecule inhibitor HS38 selectively inhibited hepatic neutrophil Irf7, mitigating liver damage. Importantly, the translational relevance of this pathway is underscored by the significant expansion of Ifit1 + neutrophils in ALF patients, where their abundance correlated with disease severity. CONCLUSIONS:These findings delineate an IRF7-Ifit1 + neutrophil-FGL2 axis driving ALF pathogenesis and establish its targeted inhibition as a viable therapeutic strategy.

Major depressive disorder (MDD) is a highly prevalent and disabling neuropsychiatric condition, its underlying molecular mechanisms remain incompletely understood. This study aimed to systematically characterize proteomic alterations in the prefrontal cortex associated with depression-like behaviors induced by chronic stress. Depression-like behaviors in mice were evaluated using standardized behavioral tests and confirmed by Digital Western blotting. Quantitative proteomic analysis of prefrontal cortex tissues was performed to compare chronic social defeat stress (CSDS) and control groups, identifying differentially expressed proteins (DEPs). These DEPs were subsequently subjected to bioinformatic analyses, including Gene Ontology (GO) enrichment and construction of protein-protein interaction (PPI) networks. Key DEPs were further validated by parallel reaction monitoring (PRM) and Western blotting. We found that CSDS mice displayed robust depression-like phenotypes, including decreased sucrose preference and increased immobility. Western blot analysis confirmed the dysregulation of ER stress markers, proinflammatory factors, and proteins related to synaptic plasticity. Proteomic analysis identified 95 differentially expressed proteins, with GO enrichment revealing predominant associations with gene regulation, mitochondrial, metabolic, and synaptic function. PPI network analysis highlighted hub proteins involved in mitochondrial, endoplasmic reticulum, and synaptic regulation. PRM and Western blot validation confirmed dysregulation in four functional modules: 1) Mitochondrial function (Mrpl17, Mrpl41)；2) Signal transduction (Rigi, Pbrm1, Plppr5, Glyr1)；3) Metabolic regulation(Pmvk, Rpl13a, Ubtd2, Tmem63b)；4) Synaptic plasticity (Kif21b, Klc4, Lama2, Col4a2). Our results demonstrate that chronic stress disrupts prefrontal cortical pathways that govern gene regulation, mitochondrial metabolism, and synaptic function, suggesting their concerted contribution to the pathophysiology of depression.

OBJECTIVE:To evaluate the impact of Jinlong capsule on the overall survival (OS) rates of patients with hepatocellular carcinoma (HCC) at various stages of the disease. METHODS:A total of 799 patients diagnosed with HCC between January 2016 and December 2019 were enrolled. The three-year OS rate of the Jinlong group (n = 144) was compared with that of the control group (n = 655). To minimize potential bias, propensity score matching (PSM) was applied. Kaplan-Meier survival analysis was used to assess the OS rates of different subgroups, with statistical significance determined by the log-rank test. RESULTS:The Cox regression model revealed that Jinlong treatment was independently associated with an improved three-year OS. The Jinlong group had a significantly higher OS rate than the control group, with an adjusted hazard ratio of 0.48 (95% confidence interval: 0.38-0.60; P <0.001). After applying PSM at a 1∶2 ratio, 140 patients were included in the Jinlong group and 280 in the control group. The OS rate for the Jinlong group was substantially longer than that for the control group (65.7% vs48.2%, P <0.0001). Additionally, the aHR for Jinlong use showed a dose-response effect: 0.36 for 3-12 months, 0.28 for 12-24 months, and 0.09 for > 24 months of use. Compared to the control treatment, Jinlong treatment consistently reduced the risk of death within three years, of most subgroups. CONCLUSIONS:Jinlong treatment significantly improved the three-year survival rate of patients with HCC. These findings provide a foundation for further studies into the effectiveness of Jinlong capsule in the treatment of HCC.

Background: The effects of depression on liver function remain unclear. This study aims to assess the impact of depression on liver function based on the NHANES 2017-2020 data analysis and two-sample Mendelian randomization analysis. And employ mediation analysis to evaluate the mediating roles of BMI, alcohol consumption and prescription drug use. Methods: Using the NHANES 2017-2020 data, linear regression and logistic regression were employed to identify the association between depression and liver function based on different variable types. Then, restricted cubic spline analysis (RCS) was used to determine whether there was a non-linear association. Subsequently, mediation analysis was conducted to clarify the mediating roles of BMI, alcohol consumption, and the application of prescription drugs in this association. Finally, Mendelian randomization (MR) analysis was used to evaluate the causal relationship of this association. Results: Depression was associated with increased ALP and GGT levels, and decreased TBIL levels, with a significant non-linear relationship. Further, body mass index (BMI), alcohol consumption, and prescription drug use mediated the relationship between depression and liver function. Lastly, two-sample MR analysis provides preliminary support for a potential causal effect of depression on liver indicators: it suggests depression may contribute to increase ALP (odds ratio [OR] = 1.044, 95% confidence interval [CI]: 1.001-1.088, p = 0.047) and GGT (OR = 1.074, 95%CI: 1.030-1.120, p < 0.001), and reduce TBIL (OR = 0.930, 95%CI: 0.902-0.958, p < 0.001). Limitations: Cross-sectional NHANES may introduce reverse causality bias; Participant exclusion and unmeasured confounders could distort association estimates; The definition of some mixed factors is not detailed enough; MR's European ancestry data limits generalizability. Conclusion: Depression was positively correlated with ALP and GGT levels, and negatively correlated with TBIL levels, with a causal link. Factors such as BMI, alcohol consumption, and prescription drug use serve as mediators of this relationship. These findings highlighted the significant effects of depression on liver function. Future studies should validate our findings in multi-ethnic cohorts and explore the direct mechanism of depression-induced TBIL reduction.

BACKGROUND:Hepatitis B virus-induced acute-on-chronic liver failure (HBV-ACLF) has extremely high mortality rates and is closely linked to inflammatory responses. Early interventions in high-risk patients can significantly improve survival rates. METHODS:In this prospective cohort study, we used the Olink proximity extension assay to compare 96 inflammation-related proteins in survivors and non-survivors of ACLF. Functional enrichment analysis of differentially expressed proteins (DEPs) was performed using KEGG to analyse their biological characteristics and correlation with disease severity. The key proteins identified in the discovery cohort (n = 32) were quantified by enzyme-linked immunosorbent assay in the modelling cohort (n = 100) to develop a machine-learning model, which was then validated in an independent cohort (n = 52). RESULT:The analysis revealed that the expression of 26 proteins was significantly elevated in non-survivors, mainly enriched in the cytokine-cytokine receptor interaction pathway. Three key proteins were highly correlated with mortality: IL-6, MMP10, and CX3CL1. The machine learning model based on these proteins accurately predicted the 90-day mortality (AUC = 0.98). Modelling and validation in both cohorts confirmed that these three indicators effectively identified high-risk patients with ACLF. CONCLUSION:IL-6, MMP10, and CX3CL1 can be used as effective biomarkers for predicting the 90-day mortality in patients with HBV-ACLF. The progression of liver failure seems to be closely related to the abnormal activation of the cytokine-cytokine receptor interaction pathway. These findings provide new directions for the study of ACLF pathogenesis and identifying potential drug targets, which are conducive to early clinical decision-making.

ObjectiveInflammatory reactions and dyslipidemia are associated with the pathogenesis and prognosis of hepatitis B virus-related cirrhosis. We aimed to assess the predictive ability of these parameters in patients with hepatitis B virus-related cirrhosis and overt hepatic encephalopathy (HBV-related OHE).DesignWe conducted an analysis of 1,404 participants diagnosed with HBV-related OHE between January 2008 and July 2023. The prognostic significance of the neutrophil-to-high-density lipoprotein cholesterol (HDL-C) ratio (NHR), lymphocyte-to-HDL-C ratio (LHR), and monocyte-to-HDL-C ratio (MHR) was evaluated using the area under the receiver operating characteristic curve (AUC). Restrictive cubic splines (RCS) were employed to explore the relationship between NHR and 12-month transplant-free (TF) mortality. This study included a prospective test cohort of 328 patients.ResultsNHR was identified as an independent risk factor for 12-month TF mortality. The AUC for NHR (0.776) was similar to that of the model end-stage liver disease (MELD) score (AUC: 0.777). In the test cohort, NHR demonstrated AUC values comparable to MELD, with significantly higher AUCs than LHR and MHR (both p < 0.05). Based on cutoff values for NHR and MELD, patients were classified into four risk subgroups: very-low (NHR < 10 and MELD <18), low (NHR ≥ 10 and MELD <18), moderate (NHR < 10 and MELD ≥18), and high (NHR ≥ 10 and MELD ≥18). The 12-month TF mortality rates in the training cohort were 7.2, 23.5, 30.8, and 51.4%, respectively, for these subgroups, while in the test cohort, the rates were 8.7, 20.5, 30.7, and 46.0%.ConclusionNHR is a valuable and accessible prognostic indicator for 12-month TF mortality in patients with HBV-related OHE. Patients with both NHR ≥ 10 and MELD ≥18 are at the highest risk of mortality.

PURPOSE:The rapid spread of the coronavirus-2019 (COVID-19) Omicron EG.5 variant poses challenges to existing treatment strategies, and comparative real-world evidence between simnotrelvir-ritonavir and nirmatrelvir-ritonavir remains limited. METHODS:We conducted a single-center retrospective study from July 01 to December 31, 2023, involving outpatient-diagnosed COVID-19 patients. We performed a descriptive analysis of epidemiologic characteristics, followed by regression analysis to identify key factors. Efficacy and safety differences between simnotrelvir-ritonavir and nirmatrelvir-ritonavir were then compared. FINDINGS:A total of 545 patients were included, with 93.21% presenting with general symptoms, 88.81% with respiratory symptoms, 10.28% with gastrointestinal symptoms, and 9.36% with cardiovascular symptoms. Factors associated with delayed recovery included a BMI over 25 kg/m2 (P = 0.004), and symptoms lasting more than 3 days at presentation (P = 0.004). The efficacy of simnotrelvir-ritonavir and nirmatrelvir-ritonavir was comparable, with mean days to symptom recovery of 5.11 and 4.22 days, respectively. However, simnotrelvir-ritonavir had a higher incidence of adverse events (20.59%) compared to nirmatrelvir-ritonavir (6.69%), primarily gastrointestinal disorders. IMPLICATIONS:During the Omicron EG.5 epidemic, general and respiratory symptoms predominated, with delayed recovery associated with being overweight, late treatment initiation, and multiple comorbidities. Simnotrelvir-ritonavir and nirmatrelvir-ritonavir demonstrated comparable efficacy, while simnotrelvir-ritonavir had a poorer safety profile.

Depression is a heterogeneous psychiatric disorder with limited treatment efficacy, as 30-50% of patients exhibit inadequate responses to conventional monoaminergic antidepressants. Rhein, a bioactive anthraquinone derived from Rheum palmatum, exhibits rapid and sustained antidepressant effects in both acute and chronic social defeat stress (CSDS) mouse models. Using quantitative proteomics on prefrontal cortex (PFC) samples from control, CSDS, Rhein-treated, and imipramine-treated cohorts, we identified differentially expressed proteins that revealed Rhein's multi-target regulatory profile. Functional enrichment and clustering analyses indicated that Rhein predominantly restores dysregulated pathways related to lipid metabolism, ribosomal translation, mitochondrial and endoplasmic reticulum (ER) function, and synaptic plasticity, forming a coherent mechanistic axis underlying its therapeutic effects. Comparative analysis with imipramine-treated mice further highlighted Rhein's distinct capacity to modulate organelle homeostasis and synaptic remodeling with greater breadth. Parallel reaction monitoring (PRM) and Western Blotting validated key proteins involved in mitochondrial functions (BNIP1, PISD, MRPL42, MRPS30, LRBA, IGHM), ER homeostasis (ACBD5, APOA4, RPL14), and synaptic plasticity (HDAC1, FAM3C, SSU72). These molecular findings suggest that Rhein exerts its antidepressant effects by restoring the functional integrity of mitochondria and the ER, thereby reprogramming synaptic plasticity. We inferred that this organelle-centered regulation further reinforces its potent modulation through multiple mechanisms and signaling pathways of synaptic plasticity, enabling Rhein to exert antidepressant effects through a coordinated, multi-layered mechanism. Collectively, our findings provide a systems-level mechanistic framework for Rhein's antidepressant efficacy and support its potential as a multi-pathway natural therapeutic, particularly for metabolic subtypes of depression.

Depressive disorders exhibit significant comorbidity with lipid dysregulation. Clinical observations indicate that poor lifestyle factors contribute to lipid dysregulation in depressed patients. This dysregulation disrupts gut microbiota homeostasis and endocrine balance. Mitochondria and endoplasmic reticulum, critical organelles for lipid metabolism, also show impaired homeostasis in depression, further contributing to lipid dysregulation. Such alterations activate peripheral and central immune-inflammatory responses, compromise blood-brain barrier integrity, and disrupt neuroimmune cytokine signaling. This process induces and aggravates neuroinflammation, thereby contributing to the onset and progression of depressive disorders. These disruptions in homeostasis further exacerbate lipid dysregulation. This review delineates the molecular mechanisms by which dysregulation of lipid metabolism exacerbates depressive disorders via neuroinflammatory pathways, offering critical insights into pathogenesis and therapeutic strategies.

BACKGROUND:Although gut microbiota has been implicated in various liver disorders, its relationship with cirrhotic portal hypertension (CPH) remains unclear. AIMS:To investigate the structural and functional alterations of gut microbiota in patients with CPH and the potential role of these alterations in the progression of CPH. METHODS:We collected faecal samples from 35 patients with CPH and 71 patients without CPH (controls) to conduct microbiome and metabolomic analyses. Gut microbes, faecal metabolites and their functional pathways associated with CPH were identified using multiple bioinformatics approaches. To understand the role of gut microbiota in the pathogenesis of CPH, we carried out faecal microbiota transplantation, CPH-characteristic bacterial transplantation and antibacterial experiments in mice. RESULTS:Microbial diversity was diminished, and gut microbial structures were altered in patients with CPH compared to the controls, primarily manifested as increased abundance of lipopolysaccharide-producing bacteria and decreased abundance of anti-inflammatory bacteria. This dysbiosis of gut microbiota was accompanied by changes in the faecal metabolome, particularly in arginine biosynthesis and nitric oxide production. Transplantation of gut microbiota from CPH patients, as well as the transplantation of CPH-associated bacteria Veillonella nakazawae, was found to exacerbate CPH progression in mice. Antibiotic treatment significantly alleviated the CPH progression induced by N-dimethylnitrosamine in mice. CONCLUSIONS:Our study reveals that gut microbiota dysbiosis is implicated in CPH progression, potentially providing new avenues for microbiome-based treatment for CPH.

BackgroundHepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is linked to dyslipidemia and inflammatory responses. This study aimed to investigate the correlation between high-density lipoprotein cholesterol (HDL-C) levels and 90-day transplant-free (TF) mortality in patients with HBV-ACLF.MethodsA prospective cohort of 287 patients with HBV-ACLF from Beijing Ditan Hospital was enrolled between January 2016 and December 2019. The prognostic accuracy of lipid profile parameters was evaluated by the area under the receiver operating characteristic curve (AUC), and the association between HDL-C levels and mortality was assessed using a restricted cubic spline analysis. Correlations between lipid profile parameters and inflammatory factors were analyzed. Kaplan–Meier curves were used to assess 90-day TF mortality, and log-rank tests were used for comparison analysis. These results were internally validated between January 2020 and December 2023 (n=125).ResultsPatients with lower HDL-C levels exhibited higher mortality rates (adjusted hazard ratio for HDL-C < 0.13 mmol/L: 4.04, 95% confidence interval: 1.35–11.85) compared with those in the reference group (with HDL-C levels above 0.36 mmol/L). An “L-shaped” association was observed between HDL-C levels and TF mortality. The prognostic value of HDL-C (AUC at day 90: 0.732) was comparable to the model for end-stage liver disease score of 0.729. Additionally, HDL-C levels were inversely correlated with interleukin (IL)-4, IL-6, and tumor necrosis factor-α (all P<0.05). In the training cohort, the 90-day TF mortality rates were 8.3%, 15.2%, 24.0%, and 43.2% for the extremely low, low, medium, and high-risk subgroups, respectively, while in the validation cohort, they were 4.5%, 18.5%, 31.2%, and 44.7%, respectively.ConclusionsHDL-C levels < 0.13 mmol/L were associated with increased 90-day transplant-free mortality in patients with HBV-ACLF. An inverse correlation was found between HDL-C levels and inflammatory markers.

Over 50% of patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) are diagnosed at an advanced stage, which is characterized by immune imbalance between CD8+ T cells and regulatory T (Treg) cells that accelerates disease progression. However, there is no imbalance indicator to predict clinical outcomes. Here, we show that the proportion of CD8+ T cells decreases and Treg cells increases in advanced HBV-HCC patients. During this stage, CD8+ T cells and Treg cells expressed the coinhibitory molecule PD-1 and the costimulatory molecule ICOS, respectively. Additionally, the ratio between PD-1+CD8 and ICOS+Tregs showed significant changes. Patients were further divided into high- and low-ratio groups: PD-1+CD8 and ICOS+Tregs high- (PD-1/ICOShi) and low-ratio (PD-1/ICOSlo) groups according to ratio median. Compared with PD-1/ICOSlo patients, the PD-1/ICOShi group had better clinical prognosis and weaker CD8+ T cells exhaustion, and the T cell-killing and proliferation functions were more conservative. Surprisingly, the small sample analysis found that PD-1/ICOShi patients exhibited a higher proportion of tissue-resident memory T (TRM) cells and had more stable killing capacity and lower apoptosis capacity than PD-1/ICOSlo advanced HBV-HCC patients treated with immune checkpoint inhibitors (ICIs). In conclusion, the ratio between PD-1+CD8 and ICOS+Tregs was associated with extreme immune imbalance and poor prognosis in advanced HBV-HCC. These findings provide significant clinical implications for the prognosis of advanced HBV-HCC and may serve as a theoretical basis for identifying new targets in immunotherapy.

Background Postoperative pulmonary complications (PPCs) extend the length of stay of patients and increase the perioperative mortality rate after video-assisted thoracoscopic (VATS) pulmonary surgery. Thoracic paravertebral block (TPVB) provides effective analgesia after VATS surgery; however, little is known about the effect of TPVB on the incidence of PPCs. The aim of this study is to determine whether TPVB combined with GA causes fewer PPCs and provides better perioperative lung protection in patients undergoing VATS pulmonary surgery than simple general anaesthesia. Methods A total of 302 patients undergoing VATS pulmonary surgery will be randomly divided into two groups: the paravertebral block group (PV group) and the control group (C group). Patients in the PV group will receive TPVB: 15 ml of 0.5% ropivacaine will be administered to the T4 and T7 thoracic paravertebral spaces before general anaesthesia induction. Patients in the C group will not undergo the intervention. Both groups of patients will be subjected to a protective ventilation strategy during the operation. Perioperative protective mechanical ventilation and standard fluid management will be applied in both groups. Patient-controlled intravenous analgesia is used for postoperative analgesia. The primary endpoint is a composite outcome of PPCs within 7 days after surgery. Secondary endpoints include blood gas analysis, postoperative lung ultrasound score, NRS score, QoR-15 score, hospitalization-related indicators and long-term prognosis indicators. Discussion This study will better evaluate the impact of TPVB on the incidence of PPCs and the long-term prognosis in patients undergoing VATS lobectomy/segmentectomy. The results may provide clinical evidence for optimizing perioperative lung protection strategies. Trial registration ClinicalTrials.gov NCT05922449 . Registered on June 25, 2023.

Background Remission is proposed as a multicomponent outcome for patients with severe asthma. Objective This post hoc analysis of QUEST (NCT02414854) and TRAVERSE (NCT02134028) evaluated whether dupilumab treatment leads to clinical asthma remission (≥12 months with no severe exacerbations, zero oral corticosteroid use, stabilized or improved lung function, patient-reported asthma control <1.5) and assessed its durability in patients with uncontrolled, moderate to severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb at parent-study baseline) who are not receiving maintenance oral corticosteroids. Methods In QUEST, patients (aged ≥12 years) were randomized to dupilumab 200/300 mg or placebo every 2 weeks for 52 weeks. In TRAVERSE, all patients received dupilumab 300 mg every 2 weeks for up to 96 weeks. We assessed the proportion of patients meeting criteria for on-treatment clinical remission up to 48 weeks of TRAVERSE. Results At QUEST baseline, 1,040 patients receiving dupilumab and 544 taking placebo had type 2 asthma; of those, 842 (dupilumab/dupilumab) and 437 (placebo/dupilumab) enrolled in TRAVERSE. At QUEST week 52 (year 1), 37.2% of patients receiving dupilumab met clinical remission criteria, compared with 22.2% taking placebo (all P < .001). At week 48 of TRAVERSE (year 2 overall), 42.8% (dupilumab/dupilumab) and 33.4% (placebo/dupilumab) of patients met clinical remission criteria. Overall, 29.5% of patients in the dupilumab/dupilumab group met the criteria at both years 1 and 2. Conclusions Dupilumab treatment enabled approximately one third of patients with type 2 asthma to meet the multicomponent end point for on-treatment clinical asthma remission for up to 2 years.

Major depressive disorder (MDD) is a common disease affecting 300 million people worldwide. The existing drugs are ineffective for approximately 30% of patients, so it is urgent to develop new antidepressant drugs with novel mechanisms. Here, we found that norisoboldine (NOR) showed an antidepressant efficacy in the chronic social defeat stress (CSDS) depression model in the tail suspension, forced swimming, and sucrose consumption tests. We then utilized the drug-treated CSDS mice paradigm to segregate and gain differential protein groups of CSDS versus CON (CSDSCON), imipramine (IMI)-treated versus CSDS (IMICSDS), and NOR-treated versus CSDS (NORCSDS) from the prefrontal cortex. These protein expression alterations were first analyzed by ANOVA with p < 0.05. The protein cluster 1 and cluster 3, in which the pattern of protein levels similar to the mood pattern, showed enrichment in functions and localizations related to mitochondrion, ribosome and synapses. Further GO analysis of the common proteins for NORCSDS groups and NORIMI groups supported the findings from ANOVA analysis. We employed Protein-Protein interaction (PPI) analysis to examine the proteins of NORCSDS and NORIMI, revealing an enrichment of the proteins associated with the mitochondrial ribosomal and synaptic functions. Further independent analysis using parallel reaction monitoring (PRM) revealed that Cox7c, Mrp142, Naa30, Ighm, Apoa4, Ssu72, Mrps30, Apoh, Acbd5, and Cdv3, exhibited regulation in the NOR-treated group to support the homeostasis of mitochondrial functions. Additionally, Dcx, Arid1b, Rnf112, and Fam3c, were also observed to undergo modulation in the NOR-treated groups to support the synaptic formation and functions. These findings suggest that the proteins involved in depression treatment exert effects in strengthen the mitochondrial and synaptic functions in the mice PFC. Western blot analysis supported the data that the levels of Mrpl42, Cox7c, Naa30, Rnf112, Dcx Apoa4, Apoh and Fam3c were altered in the CSDS mice, and rescued by NOR treatment, supporting the PRM data. NOR treatment also rescued the NLRP3 inflammasome activation in CSDS mice. In summary, the current proteomic research conducted on the prefrontal cortex has provided valuable insights into the specific and shared molecular mechanisms underlying pathophysiology and treatment to CSDS-induced depression, shedding light on the therapeutic effects of Norisoboldine.

Major depressive disorder (MDD) is a common disease affecting 300 million people worldwide. Current drugs are ineffective for at least 30% of the patients. Novel and personalized medication is needed urgently. Cumulative studies suggest that the neuroinflammation of the glial cells, particularly NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation and subsequent regulation of synaptic functions may be the key for the pathophysiology and treatment of MDD. In this review, we delve to compare the modern mechanism of MDD treatment with the theories of differential symptoms for personalized treatment of the ancient decoctions from traditional Chinese Medicine (TCM). Interestingly, the mechanisms of MDD treatment from Western and TCM theories overlap to a nexus on regulating neuro-immune signaling pathways, including NLRP 3 inflammasome, cytokine expressions and synaptic functions. In this review, we have summarized 8 differential syndromes and 10 decoctions for the TCM treatment of MDD in modulation of immune system and synaptic functions. The neuroimmune modulation of the 10 decoctions for the treatment MDD from TCM are amazingly similar towards the anti-inflammatory effects and enhancing synaptic functions. The comparison of theories and therapies from Western medicine and TCM may contribute to the development of more effective and safer medication for MDD.

Purpose:Despite the implementation of various insulation measures, the incidence of hypothermia during thyroid surgery remains high. This randomized controlled study aimed to evaluate the effects of aggressive thermal management combined with resistive heating mattresses to prevent perioperative hypothermia in patients undergoing thyroid surgery. Patients and Methods:142 consecutive patients scheduled for elective thyroid surgery were enrolled in the study. They were randomly and equally allocated to the aggressive warming or routine care groups (n = 71). The patients' body temperature was monitored before the induction of anesthesia until they returned to the ward. The primary outcome was the incidence of perioperative hypothermia. Secondary outcomes included postoperative complications, such as mortality, cardiovascular complications, wound infection, shivering, postoperative nausea and vomiting (PONV), visual analog scale (VAS) pain scores, fever, headache and hospital length of stay (LOS). Results:In our study, the results showed that a significantly higher rate of hypothermia was observed in the routine care group compared with the aggressive warming group. The incidence of perioperative hypothermia was 19.72% (14/71) in the aggressive warming group and 35.21% (25/71) in the routine care group (P < 0.05). The incidence of shivering in the aggressive warming group (1.41%) was significantly lower than that in the routine care group (11.27%) (P < 0.05), and a one-day reduction in hospital length of stay was observed in the aggressive warming group (P < 0.05). There was no significant difference in mortality or other postoperative complications, such as cardiovascular complications, wound infection, PONV, pain, fever or headache, between the two groups (P > 0.05). Conclusion:Our results suggest that aggressive thermal management combined with resistive heating mattresses provided improved perioperative body temperature and reduced the incidence of perioperative hypothermia and shivering compared to routine thermal management.

Purpose: Global prevalence of pediatric asthma and associated morbidity and mortality has continuously increased. Asthma is the most common chronic illness in children in the UK; however, recent epidemiology data are lacking. This analysis describes the overall prevalence and burden of illness of asthma in children. Methods: This was a retrospective, longitudinal, database analysis using the Clinical Practice Research Datalink database. Primary care records of 19,330 patients (6-11 years) between January 1 and December 31, 2017, were analyzed. Asthma prevalence was assessed by severity (as described by Global Initiative for Asthma 2017 guidelines), and symptoms, comorbidities, and treatments were compared between asthma patients and matched non-asthmatic controls. Results are presented descriptively; logistic regression analyses were performed for asthma symptoms. Results: The estimated prevalence of pediatric asthma was 6.5% (95% CI: 6.4-6.5) in the UK (mild: 74.2%; moderate: 15.0%; severe: 10.8%). All patients with moderate or severe asthma and 72.5% of patients with mild asthma were prescribed drug therapy. Most patients with moderate or severe asthma were prescribed a short-acting beta 2-agonist (94.9% and 96.0%, respectively), compared with 69.2% of mild asthma patients. Daytime symptoms were reported by 78.1% in those with severe asthma; 34.9% reported night-time symptoms and 30.8% reported an impact on usual activities. Asthma patients had a higher baseline prevalence of comorbidities compared with non-asthmatic controls, notably atopic dermatitis (47.8% in severe asthma versus 20.8% in controls) and allergic rhinitis (13.3% in severe asthma versus 2.0% in controls). Conclusion: This analysis confirmed that asthma remains a common morbidity among children in the UK. Increasing asthma severity was associated with worsening symptoms, and asthma patients had significantly more comorbidities compared with non-asthmatic controls.

Patients with uncontrolled, moderate-to-severe asthma have a higher risk for exacerbations, negatively impacting lung function and quality of life. Dupilumab, a fully human monoclonal antibody, blocks interleukins 4 and 13, key and central drivers of type 2 inflammation. Dupilumab has been effective in the treatment of certain types of moderate-to-severe asthma across several clinical trials. We describe the characteristics of patients enrolled in RAPID, a global prospective registry, who initiated dupilumab (primary indication: asthma) in a real-world clinical setting. A total of 205 patients (aged ≥ 12 years) were enrolled between March 2020 and October 2021 and are included in this analysis. Data are shown as mean (SD) unless stated otherwise. Patients were aged 50.1 (17.4) years and were mostly female (65.4