First Affiliated Hospital of Guangzhou University of Chinese Medicine

Asthma-associated airway mesenchymal reprogramming refers to a dynamic pathological process characterized by persistent pathological alterations in phenotype, function, and intercellular interactions of airway mesenchymal cells under asthmatic conditions, which actively drive airway structural changes, airway narrowing, and impaired lung function. It is considered one of the key pathological mechanisms driving the chronic progression of asthma and contributing to persistent airflow limitation. Oxidative stress, as a central pathogenic factor, drives asthma-associated airway mesenchymal reprogramming through multiple mechanisms, including promoting inflammation, inducing epithelial-to-mesenchymal transition (EMT), exacerbating airway smooth muscle dysfunction, and impairing endogenous antioxidant defense systems. Increasing evidence suggests that this reprogramming may initiate at early stages of asthma, highlighting its potential relevance as an early pathogenic indicator. Although standard therapies such as inhaled corticosteroids and β2-agonists are effective in controlling acute inflammation, they show limited efficacy in effectively modulating or substantially improving established mesenchymal reprogramming. Traditional Chinese Medicine (TCM), with its long history of use in asthma, offers a complementary therapeutic approach due to its multi-component, multi-target actions, low adverse effect profile, and anti-inflammatory, antioxidant, and modulatory effects on airway mesenchymal reprogramming. This review focuses on the potential of metabolites originating from botanical drugs used in TCM and botanical drug formulations in modulating oxidative stress to intervene in asthma-associated airway mesenchymal reprogramming, providing comprehensive evidence to support mechanistic investigation and translational research in managing this key pathological process.

The neoadjuvant chemoradiotherapy (nCRT) might accentuate surgical complications and toxicity in the treatment of locally advanced rectal cancer (LARC) while neoadjuvant chemotherapy (nCT) alone shows promise as an alternative treatment. However, which patients deserve most from the nCT need further clarify. This trial aimed to assess the non-inferiority of nCT with capecitabine plus oxaliplatin (CAPOX) versus nCRT with capecitabine in LARC with uninvolved mesorectal fascia (MRF). Patients with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to receive 4 cycles of CAPOX chemotherapy alone (nCT group) or CRT with concurrent Capecitabine (nCRT group). The primary end point is 3-year locoregional recurrence-free survival (LRRFS). Secondary end points, such as 3-year disease-free survival (DFS), 3-year overall survival (OS), and adverse events (AEs), were also reported. A total of 663 patients were enrolled and 589 patients received the allocated treatment (nCT, n = 300; nCRT, n = 289). LRRFS was analyzed with a median follow-up of 48 months. 3-year LRRFS was 97.4% (95% CI, 95.5 to 99.3) in the nCRT group and 96.3% (95% CI, 94.0 to 98.6) in the nCT group, resulting in a hazard ratio (HR) of 1.40 (95% CI, 0.53 to 3.68). The nCT and nCRT achieved similar 3-year DFS (89.2% v 87.9%; HR, 0.88 [95% CI, 0.54 to 1.44]) and 3-year OS (95.0% v 94.1%; HR, 0.86 [95% CI, 0.42 to 1.76]). The nCT group showed a lower incidence of grade 2 to 4 long-term AEs (16.0% v 26.3%, P = 0.002) and proctitis (33.6% v 41.7%, P = 0.049) compared with nCRT group. The non-inferiority of nCT was not confirmed with a very low incidence of local recurrence in both group. But nCT offers comparable DFS and OS while mitigating the burden of toxicity as compared to nCRT. These insights shed light on a potential paradigm shift in the treatment for LARC with uninvolved MRF.

Subthreshold depression (StD) confers a high risk for major depression and is characterized by substantial individual clinical heterogeneity. However, the neurobiological substrates underlying this heterogeneity remain largely unknown. Using a large multisite resting-state functional MRI dataset including 1203 healthy participants and 197 individuals with StD, we constructed connectome-based normative models to identify individual brain deviations and biotypes in StD. We highlighted remarkable individual variability in the connectome deviations in StD, leading to the identification of two distinct biotypes. Subtype 1 exhibits severe positive deviations primarily in the default mode regions and negative deviations in the sensorimotor and ventral attention areas, while subtype 2 shows a moderate but opposite deviation pattern. The two subtypes differ significantly in depressive symptoms, gene expression profiles, and treatment responses to bright light therapy. These findings highlight the neurobiological underpinnings of the clinical diversity in StD, emphasizing the necessity for developing personalized interventions for this condition.

Frailty is a multidimensional state related to multidomain risk factors, including demographic, physical, and psychological variables. The risk factors affecting frailty in postoperative older patients and the interactions between these factors remain unclear. Network analysis provides a novel method for conceptualizing interconnections among complex multidimensional data. This study aimed to explore the relationships between demographic, physical, psychological, surgery-related factors and frailty in postoperative older adults. The Early-Warning model of Perioperative Adverse Events for older adults (EPAE) is an prospective, multicenter, observational study. Participants were assessed for demographic variables, clinical and physical variables, psychological and cognitive variables, surgery-related variables, and frailty assessment during the period of hospitalization. A perioperative network was constructed to identify key risk factors associated with postoperative frailty and specific paths within the network. 2678 older adults were enrolled in the study. Postoperative frailty in older adults was strongly associated with postoperative activities of daily living (ADL) (average edge Weight=-0.26), Morse Fall Scale (MFS)(average edge Weight = 0.19), Hemoglobin(Hb) (average edge Weight=-0.16), Patient Health Questionnaire-9(PHQ-9)(average edge Weight = 0.14), and Mini-Cog(average edge Weight=-0.1). PHQ-9 played mediating roles between Feeling nauseated, Emesis, physical Exam, and Duration of symptoms score (I-FEED) and frailty, Athens Insomnia Scale(AIS) and frailty. Postoperative frailty, Social supporting rating scale(SSRS), PHQ-9, and Mini-Cog were the strongest bridge symptoms in the network. Postoperative frailty was the most prominent bridge symptom in the perioperative network, which was strongly associated with postoperative physical(ADL, Hb, MFS) and psychological factors(PHQ-9 and Mini-Cog). Depression may mediate the associations between postoperative clinical symptoms(gastrointestinal dysfunction and insomnia) and postoperative frailty. Our findings support a clarion call for dynamic assessments for postoperative frailty, and intervention programs targeting specific frailty-related factors, especially depression, to prevent or reverse frailty for older adults after surgery. This study was registered in the Chinese Clinical Registry Center (registration no. ChiCTR2300071535). Date: 17-5-2023.