Tang Du Hospital

BackgroundOptimizing the length of hospital stay (LOHS) after total knee arthroplasty (TKA) is essential for improving healthcare efficiency. The effect of anesthesia method on LOHS remains controversial and challenging to accurately assess using conventional statistics. This study leverages robust machine learning with dedicated feature selection to clarify its impact within a limited but well-characterized patient cohort.MethodsWe analyzed data from 157 patients undergoing primary unilateral TKA. The Boruta algorithm—a robust feature selection method based on Random Forest—was employed to identify the most predictive variables for LOHS from perioperative parameters. Four machine learning models (Linear Model, Random Forest, XGBoost, and K-Nearest Neighbors) were built using Boruta-confirmed features and evaluated via 10-fold cross-validation.ResultsGeneral anesthesia (GA) was associated with significantly longer LOHS (15.93 ± 4.04 days) compared to intrathecal anesthesia (IA) (14.31 ± 4.09 days, p = 0.012). The Boruta algorithm confirmed anesthesia method as an important predictor, along with age and preoperative hospitalization duration. While the Linear Model offered the best interpretability (mean R2 = 0.475), XGBoost showed a strong ability to model nonlinear patterns. Subgroup analyses revealed that GA was linked to prolonged anesthesia time, higher blood loss, and increased transfusion requirements, factors that are collectively associated with extended hospitalization.ConclusionDespite the limited sample size, the use of Boruta feature selection ensured model focus on clinically meaningful predictors. We identify anesthesia method as a key modifiable factor associated with LOHS after TKA. These data-driven insights support the preferential consideration of IA for eligible patients in similar clinical contexts to potentially shorten hospital stays and optimize resource use, demonstrating the value of explainable machine learning in small-sample clinical studies.

ABSTRACT Aims The tolerance of patients with compensated hepatitis B cirrhosis to interferon (IFN) therapy remains controversial. Therefore, this study aimed to evaluate the safety of pegylated interferon‐alpha in chronic hepatitis B (CHB) patients with compensatory cirrhosis. Methods Data from two prospective cohorts (the OASIS Project and CHESS 2306) from January 2018 to January 2024 were synthesized and analyzed. Patients with Child‐Pugh Class A hepatitis B cirrhosis who received IFN‐based therapy ( n = 920) were included. The control groups included patients with compensated hepatitis B receiving nucleos(t)ide analog (Nuc) monotherapy ( n = 714) and patients without cirrhosis receiving IFN‐based therapy ( n = 4111), respectively. Propensity score matching was used to control for confounding factors; 566 versus 566 cases were analyzed among patients with cirrhosis treated with IFN‐based therapy or Nuc monotherapy, and 785 versus 785 cases were analyzed among patients with and without cirrhosis treated with IFN‐based therapy. Primary outcomes included decompensation events, and secondary outcomes included severe adverse events, overall adverse events, and treatment‐related hospitalizations or deaths. Results In patients with hepatitis B virus‐related cirrhosis, the incidence of decompensation events was similar between IFN‐based therapy and Nuc monotherapy (6/566 [1.1%] vs. 3/566 [0.5%], p = 0.506). No hospitalizations or deaths were associated with adverse events during the observation period (48 weeks). The incidences of severe adverse events were similar in patients with cirrhosis under IFN‐based therapy or Nuc monotherapy (severe neutropenia: 1/450 [0.2%] vs. 0/378 [0], p = 0.999; severe thrombocytopenia: 4/435 [0.9%] vs. 0/296 [0], p = 0.153; severe alanine aminotransferase level elevation: 1/523 [0.2%] vs. 1/458 [0.2%], p = 0.999; and severe total bilirubin [TBIL] level elevation: 5/419 [1.2%] vs. 3/385 [0.8%], p = 0.727). The incidences of severe adverse events were similar between patients with and without cirrhosis receiving IFN‐based therapy, except that severe TBIL level elevation was more frequent in patients with cirrhosis who already had mildly to moderately elevated TBIL levels at baseline than in those without (6/153 [3.9%] vs. 0/118 [0], p = 0.040). Conclusion IFN‐based therapy demonstrates favorable safety in Child‐Pugh A compensated cirrhosis. It did not increase decompensation events or severe adverse events compared to Nuc monotherapy, and adverse event profiles were largely similar between cirrhotic and non‐cirrhotic patients, except for a higher risk of severe hyperbilirubinemia in those with pre‐existing TBIL elevation. ClinicalTrials.gov identifier: NCT04896255. Chinese Clinical Trial Registry number: ChiCTR2500107592.

The global tuberculosis (TB) epidemic imposes a substantial burden. As a high-burden country, China faces a significant gap from the World Health Organization (WHO)'s 2025-2030TB prevention and control targets. This study analyzed the temporal trends of TB epidemiology in mainland China to provide an evidence base for the early achievement of TB control goals. We integrated TB surveillance data (2004-2024) from the National Health Commission of the People's Republic of China and population data from the National Bureau of Statistics. Joinpoint regression was used to identify trend changes, with the average annual percent change (AAPC) quantifying trend magnitudes. Interrupted time series model was applied to assess intervention effects, and seasonal autoregressive integrated moving average models were employed to predict future incidence and mortality trends. A total of 19.4854 million cumulative TB cases and 508,000 cumulative deaths were reported during 2004-2024. The incidence rate decreased from 74.644 to 49.888 per 100,000 population (AAPC = -2.83%, P < 0.001), showing a "winter peak and summer trough" pattern-with a 32.7% higher incidence in winter than in summer. The mortality rate first decreased and then increased: it declined immediately after the full coverage of Directly Observed Treatment, Short-course in 2010 but rose to 0.283 per 100,000 population after 2021. Projections indicate that the achievement rate of the WHO incidence target will be only 43.24% by 2025 (target: 31.708 per 100,000 population) and 39.48% by 2030 (target: 12.683 per 100,000 population). The mortality rate is projected to reach 0.333 per 100,000 population by 2030, compared with the target of 0.013 per 100,000 population. Despite notable achievements in TB control in China, significant gaps remain from the WHO's targets. It is imperative to strengthen precision stratification-based prevention and control, establish a TB diagnosis and treatment guarantee mechanism, and implement remote supervision relying on informatization.

Pancreatic ductal adenocarcinoma (PDAC) is characterised by a dismal prognosis and insensitivity to immune checkpoint blockers (ICBs); however, the underlying mechanism remains elusive. This study aimed to identify tumour cell-intrinsic regulators that promote immune evasion and ICB resistance in PDAC. Multi-omics analysis and clinical cohort studies identified protein disulfide isomerase family A member 6 (PDIA6) as a regulator of the immune microenvironment. Flow cytometry, multiplex immunohistochemistry, electron microscopy and Glutathione S-Transferase (GST) pulldown assays confirmed that PDIA6 repressed PRKR-like endoplasmic reticulum kinase (PERK) activation and immunogenic cell death (ICD). Chromatin immunoprecipitation confirmed that KRASG12D and YY1 modulated PDIA6 transcription. LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre (KPC) mouse models showed that PDIA6 inhibition improved ICB response. Multi-omics screening identified PDIA6 as a biomarker of CD8+ T-cell paucity and poor prognosis in patients with PDAC. High PDIA6 levels predicted poor ICB response in the PDAC cohorts. PDIA6 inhibition reprogrammed the immunosuppressive tumour microenvironment and hindered mouse PDAC growth in the presence of CD8+ T-cell, which is attributed to enhanced ICD. PDIA6 interacted with cysteine 453 of PERK, abrogating the disulphide bond-mediated dimerisation and activation of PERK, an ICD inducer. Oncogenic KRASG12D potently upregulated PDIA6 via YY1-mediated transcriptional activation. We identified a small-molecule inhibitor of PDIA6, PACMA31, and demonstrated that targeting PDIA6 with PACMA31 improved ICB efficacy in a PDAC mouse model with KRAS mutations. PDIA6, driven by KRASG12D, alleviates ICD and promotes immune evasion, functioning as a predictive biomarker to screen ICB-sensitive patients and a therapeutic target to improve ICB efficacy in PDAC with KRAS mutations.

Inflammatory dermatoses like psoriasis and atopic dermatitis are prevalent autoimmune disorders whose management is challenged not only by inflammatory lesions but, more significantly, by persistent pruritus and frequent relapse following treatment discontinuation. The pathogenic progression of these dermatoses is critically influenced by an imbalance between pro-inflammatory adenosine triphosphate (ATP) and anti-inflammatory cyclic adenosine monophosphate (cAMP), alongside reactive oxygen species (ROS) accumulation. To address this imbalance and effectively scavenge ROS, we have developed AC@Mg/Ce-UiO, integrating adenylate cyclase (AC) with a defect-engineered Mg/Ce-UiO nanozyme, for inflammatory dermatosis treatment and recurrence prevention. Mg/Ce-UiO nanozyme, synthesized through a metal-substitution strategy, demonstrates enhanced superoxide dismutase-like and catalase-like activities, facilitating efficient ROS scavenging. Concurrently, the encapsulated AC enzyme catalyzes the conversion of ATP into cAMP. Both in vitro and in vivo studies demonstrate that AC@Mg/Ce-UiO markedly downregulates the expression of inflammatory cytokines and pruritogens, inhibits keratinocyte hyperproliferation, and diminishes the infiltration of immune memory T cells. Consequently, this nanozyme not only alleviates psoriatic symptoms (e.g., lesions and pruritus), but also decreases the likelihood of recurrence. This study introduces a safe and potent dual-catalytic therapy that targets the fundamental pathogenesis of inflammatory dermatoses, providing a promising strategy for achieving long-term remission and preventing recurrence.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s12951-026-04130-w.