BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

In January 2025， the European Society for Medical Oncology （ESMO） released the ESMO clinical practice guideline interim update on the management of biliary tract cancer as a supplementary update to Biliary tract cancer： ESMO clinical practice guideline for diagnosis， treatment and follow-up published in November 2022. This interim update mainly revises the latest evidence-based medical recommendations in the key fields of molecular diagnostics and clinical management since the release of the original guidelines， and it is not a comprehensive update of the entire document. This article summarizes and makes an excerpt of the new recommendations from this interim update.

Objective To examine the current status and trends of colorectal cancer (CRC) burden among Chinese residents from 1990 to 2021. Methods Data on CRC burden in China, Asia, and the global population from 1990 to 2021 were retrieved from the Global Burden of Disease database for descriptive analysis. An age-period-cohort model was employed to estimate the effects of age, period, and cohort on CRC mortality and to forecast changes in disease burden. Results In 2021, China’s age-standardized mortality rate, prevalence rate, and DALY rate for CRC were higher than global and Asian averages. The estimated annual percentage changes (EAPC) from 1990 to 2021 were −0.49% (95%CI: −0.55% to −0.43%) for mortality, 3.17% (95%CI: 3.03%−3.31%) for prevalence, and −0.62% (95%CI: −0.71% to −0.54%) for DALYs. Areas with high and medium-high sociodemographic indexes (SDIs) showed significant decreases in standardized mortality and DALY rates, but these rates remained higher compared with other regions. CRC mortality increased with age in the Chinese population, more prominently in males than in females. Using the 2002–2006 period as a reference (RR=1), the period effect on CRC mortality risk for women was higher than that for men until 2004, after which it declined considerably. With the 1957 birth cohort as a reference (RR=1), CRC mortality risk generally decreased across subsequent birth cohorts. Predictions indicate that by 2035, the standardized prevalence rate will be 267.21 per 100 000, and the standardized mortality rate will be 12.29 per 100 000. Conclusion From 1990 to 2021, China’s age-standardized CRC mortality and DALY rates have decreased, while the standardized prevalence rate has increased. These findings suggest the government to establish a comprehensive multi-level CRC prevention network.

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

To investigate the effect of Xuebijing injection (XBJ) on cGAS/STING pathway in alleviating sepsis-induced acute lung injury (ALI), the mouse sepsis-induced ALI model was established by cecal ligation and puncture (CLP), and the cell inflammation model was constructed by LPS stimulating RAW264.7 cells. The effects of XBJ on lung tissue injury and cGAS/STING pathway-related protein expression in septic mice were investigated by HE staining, ELISA, and Western blot. The results showed that XBJ intervention could alleviate lung tissue injury, reduce serum IL-6, TNF-α, IFN-β, IL-1-β levels, and the expression of cGAS, STING, p-TBK1, and p-IRF3 proteins in lung tissue in vivo, and reduce the mRNA level of related inflammatory factors in RAW264.7 cells and the expression of cGAS/STING pathway proteins in vitro. The results showed that XBJ could play a role in the prevention and treatment of sepsis-induced ALI by inhibiting the inflammatory response via inhibition of the activation of cGAS/STING pathway. This study provides a new molecular mechanism for the clinical prevention and treatment of sepsis-induced acute lung injury with XBJ.

Objective To investigate the clinical manifestations and prognosis of patients with anti-leucine rich glioma inactivated 1（LGI1）antibody encephalitis. Methods A retrospective analysis was performed for the data of patients with anti-LGI1 antibody encephalitis who were hospitalized in Department of Neurology，Xuanwu Hospital，Capital Medical University，from September 2019 to December 2023，including clinical features，treatment，and prognosis. Results A total of 80 patients were enrolled，including 48 male patients and 32 female patients. Of all 80 patients，51（63.8%）had the initial symptom of epilepsy，13（16.3%）had the initial symptom of faciobrachial dystonic seizures，26（32.5%）had the initial symptom of cognitive impairment，and 12（15%）had the initial symptom of mental and behavioral disorders. As for comorbidities，there were 28 patients（35%）with hyponatremia，22（27.5%）with Hashimoto's thyroiditis，and 5（6.25%）with tumor. All 80 patients tested positive for serum LGI1 antibody，and 69（86.3%）tested positive for LGI1 antibody in cerebrospinal fluid. Among the 80 patients，37（46.25%）had abnormalities on magnetic resonance imaging，and 30 had abnormalities on 18F-FDG PET/CT. There were 50 patients with abnormalities on video electroencephalography. A total of 77 patients received first-line immunotherapy，and after follow-up for 1 year，19.4% of the patients had the sequela of seizure，59.7% of the patients had deterioration of the memory，and 48.6% of the patients had mental and behavioral disorders. Conclusion Epilepsy，cognitive impairment，and mental and behavior disorders are the most common manifestations of anti-LGI1 antibody encephalitis. There is generally a good prognosis after immunotherapy，with the sequelae of cognitive impairment and mental and behavioral disorders.

OBJECTIVE To analyze chemical components of Yao ethnic medicine Pittosporum pauciflorum， establish its fingerprint and investigate the spectrum-effect relationship of its anti-inflammatory effect. METHODS UHPLC-Q-Orbitrap-MS technology was used to analyze the chemical components of P. pauciflorum （batch S6）. The fingerprints for 10 batches of P. pauciflorum from different producing areas in Guangxi Province （batches S1-S10） were established by HPLC， and similarity assessment and chemometric pattern recognition analysis were conducted. RAW264.7 inflammatory cell model was induced by lipopolysaccharide， and the anti-inflammatory activity of P. pauciflorum was investigated. Using inhibition rates of nitric oxide （NO）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β as efficacy indicators， grey relational analysis and partial least squares regression analysis were adopted to evaluate the spectrum-effect relationship of the anti-inflammatory effect of P. pauciflorum. RESULTS There were 60 chemical components， including flavonoids， phenolic acids， lipids， etc.， identified in P. pauciflorum. The fingerprints for 10 batches of P. pauciflorum showed 14 common peaks，with similarity values ranging from 0.883 to 0.991. Three common peaks were assigned neochlorogenic acid （peak 5）， chlorogenic acid （peak 7）， and syringaldehyde （peak 10）. The classification results of the systematic clustering analysis and the principal component analysis were basically consistent. Batches S1 to S10 of P. pauciflorum significantly reduced the levels of NO， TNF-α， IL-6 （except for batch S5） and IL-1β in the cell supernatant （P＜0.05 or P＜0.01）. Inhibition rates of above inflammatory indexes were 10.26%-39.96%， 14.96%-31.36%， 1.38%-21.27%， 18.54%-28.00%， respectively. The contents of neochlorogenic acid， syringaldehyde， as well as the components corresponding to peaks 1， 3， 9， 12 and 14，exhibited a strong correlation with the anti-inflammatory effects of P. pauciflorum. CONCLUSIONS The present study has analyzed the chemical components of P. pauciflorum and established HPLC fingerprints for 10 batches of P. pauciflorum. Each batch of medicinal herbs demonstrates certain anti- inflammatory activities， among which neochlorogenic acid， syringaldehyde， and the components corresponding to peaks 1， 3， 9， 12 and 14 are likely to be the active anti-inflammatory components.

Objective: To compare the biological characteristics of human induced pluripotent stem cell-derived platelet exosomes (hiPSC-Plt-Exos) with those of conventional apheresis platelet exosomes (Plt-Exos), specifically focusing on their differential abilities to enhance the proliferation and migration of human umbilical cord mesenchymal stem cells (hUC-MSCs). Methods: Exosomes were isolated from hiPSC-derived Plt and apheresis Plt concentrate using size exclusion chromatography. These exosomes were then characterized through nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. Co-culture experiments into hUC-MSCs were conducted with hiPSC-Plt-Exos and apheresis Plt-Exos, respectively. Their effects on the proliferation and migration of hUC-MSCs were assessed via cell proliferation assays and scratch tests. Results: hiPSC-Plt-Exos and apheresis Plt-Exos exhibited comparable particle sizes, morphological features (such as the characteristic cup-shaped structure), and surface markers (including CD9 and HSP70). Notably, hiPSC-Plt-Exos demonstrated a significantly greater ability to enhance the proliferation and migration of hUC-MSCs compared to apheresis Plt-Exos (P<0.05). These differences provide critical comparative data for their application in various clinical contexts. Conclusion: This study establishes a theoretical foundation for developing precise therapeutic strategies based on hiPSC-Plt-Exos. Furthermore, it underscores the necessity of selecting the appropriate type of exosomes according to the specific disease microenvironment to achieve optimal therapeutic outcomes.

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult