Shaoqi Tian

DNA virus-associated tumours represent an important component of the global burden of infection-associated cancer. Studies of classical DNA tumour viruses have defined major oncogenic routes, including persistent viral oncoprotein expression, chronic inflammation and tissue regeneration, viral integration and immune evasion. This work has also facilitated clinical applications of vaccines, antiviral therapies and viral biomarker testing. Recent advances in cancer genomics and molecular pathology have identified several biologically distinctive virus–tumour associations. These include TTMV::RARA fusion-driven APL-like acute myeloid leukaemia, HPV42-associated digital papillary adenocarcinoma, AAV2 insertions in a subset of hepatocellular carcinomas and transplant-associated BKPyV-positive urothelial carcinoma. The significance of these associations lies not in expanding the catalogue of tumour viruses, but in revealing distinct molecular events. These encompass virus–host fusion, tissue-specific viral oncogene expression, insertion-mediated cis activation and persistent T-antigen expression under immunosuppression. Here, we outline the principal mechanisms of classical DNA tumour viruses and compare the molecular basis, modes of tumour maintenance and potential clinical value of these recently recognised associations. We also discuss detection strategies, evidentiary boundaries and priorities for future research. Current evidence indicates that event-matched assays may support specialist ancillary diagnosis or molecular classification in selected settings, particularly for APL-like leukaemia and DPA. However, none of the four emerging associations currently supports population screening or a virus-directed standard therapy, and research-stage applications require prospective validation.

Purpose: This study aimed to evaluate the therapeutic efficacy of chelidonic acid (CA) in Aspergillus fumigatus ( AF )-induced keratitis and to elucidate the underlying molecular mechanisms. Methods: The safety of CA was assessed using a Cell Counting Kit-8 (CCK-8) assay, live-dead cell staining, cell scratch assay, corneal fluorescein sodium staining, and hematoxylin-eosin (HE) staining. The antifungal activity of CA was determined using minimum inhibitory concentration (MIC) assays, calcofluor white staining, propidium iodide (PI) staining, quantification of corneal fungal burden, periodic acid-Schiff (PAS) staining and quantitative real-time polymerase chain reaction (qRT-PCR). The therapeutic efficacy of CA was evaluated by slit-lamp biomicroscopy, corneal clinical scoring, HE staining, immunofluorescence staining, myeloperoxidase (MPO) measurement, and Transwell migration assay. The anti-inflammatory activity of CA was determined by qRT-PCR, western blotting, and immunofluorescence staining. The therapeutic efficacy of combined CA and natamycin treatment was assessed by slit-lamp examination, corneal clinical scoring, PAS staining, and HE staining. Results: 5 mM CA exhibited no detectable cytotoxicity in RAW264.7 cells, human corneal epithelial cells (HCECs) or mouse corneas. CA exerted antifungal effects in AF keratitis. CA significantly ameliorated AF keratitis by suppressing neutrophil and macrophage infiltration. CA markedly downregulated the expression of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), and upregulated the expression of anti-inflammatory cytokine IL-10, through inhibition of the myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway. Combined treatment with CA and natamycin further reduced clinical scores, fungal load, and inflammatory cell infiltration compared with monotherapy. Conclusions: CA exhibits both antifungal and anti-inflammatory activities in AF keratitis and represents a promising candidate for the treatment of fungal keratitis.

Objective: To investigate the associations of the preoperative D-dimer-to-albumin ratio (DAR) and prognostic nutritional index (PNI) with aseptic wound complications (AWC) and periprosthetic joint infection (PJI) after primary total knee arthroplasty (TKA), and to evaluate their within-sample discrimination for distinct postoperative adverse outcomes. Methods: This single-center retrospective cohort study included patients who underwent primary unilateral TKA at the Affiliated Hospital of Qingdao University between April 2019 and January 2024. Patients with both AWC and PJI were classified in the PJI group only. Deep venous thrombosis was excluded preoperatively using lower-extremity color Doppler ultrasonography. DAR and PNI were calculated from laboratory tests obtained within 48 h before surgery. AWC was assessed within 30 days after surgery, and PJI was assessed within 2 years according to the 2018 International Consensus Meeting criteria. Multivariable logistic regression, receiver operating characteristic (ROC) analysis with 95% confidence intervals (CIs), DeLong tests, bootstrap internal validation, calibration assessment, and sensitivity analyses were performed. Results: A total of 1,197 patients were included, including 45 isolated AWC events and 35 PJI events. After adjustment for age, sex, body mass index, diabetes mellitus, and Charlson Comorbidity Index, preoperative PNI was independently associated with isolated AWC (odds ratio [OR], 0.613; 95% CI, 0.543–0.693; P < 0.001), whereas preoperative DAR was not associated with isolated AWC (OR, 0.952; 95% CI, 0.852–1.064; P = 0.388). In contrast, DAR was independently associated with PJI (OR, 1.454; 95% CI, 1.328–1.592; P < 0.001), whereas PNI was not significantly associated with PJI (OR, 0.915; 95% CI, 0.825–1.015; P = 0.094). PNI showed an AUC of 0.873 (95% CI, 0.792–0.955) for isolated AWC, and DAR showed an AUC of 0.920 (95% CI, 0.865–0.975) for PJI. Bootstrap optimism-corrected AUCs were 0.862 for the adjusted PNI-AWC model and 0.900 for the adjusted DAR-PJI model. Conclusions: In this exploratory single-center retrospective cohort, preoperative PNI was more strongly associated with isolated AWC, whereas preoperative DAR was more strongly associated with PJI. Although both markers showed good apparent discrimination and high negative predictive values, the low event numbers, limited positive predictive values, imperfect calibration, and absence of external validation require cautious interpretation. Larger multicenter prospective studies are needed before these cutoffs can be applied as clinical decision thresholds.

Introduction: Postoperative delirium (POD) is a common and serious postoperative complication, with an incidence of approximately 30% among older adults undergoing gastrointestinal surgery. Serotonin has been implicated in a variety of neuropsychiatric disorders. Gastrointestinal surgery has been shown to increase serotonin synthesis and release from enterochromaffin cells; however, the causal relationship between serotonin and POD remains unclear. This study aims to investigate the causal relationship between peripheral serotonin levels and POD in older adults undergoing gastrointestinal surgery. Methods and analysis: This single-centre prospective cohort study will enrol 314 patients aged ≥60 years who are undergoing elective gastrointestinal surgery at the Affiliated Hospital of Qingdao University between December 2025 and December 2026. Peripheral serotonin levels will be measured prior to anaesthesia induction and prior to discharge from the post-anaesthesia care unit. The primary outcome will be the incidence of POD within 3 days. Secondary outcomes will include emergence agitation, number of POD episodes, POD onset time and duration, POD severity and subtype, pain scores, quality of recovery, gastrointestinal function and postoperative complications. A predefined directed acyclic graph will be used to guide covariate adjustment. Statistical analyses will include multivariate logistic regression, linear trend analysis, restricted cubic spline modelling, subgroup analyses, sensitivity analyses and Bayesian mediation analysis. Delirium assessors will undergo standardised training conducted by psychiatrists to ensure diagnostic reliability. Ethics and dissemination: The study protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University (Approval No. QYFYEC2025-199) and was registered with the Chinese Clinical Trial Registry (Registration ChiCTR2500112152). Written informed consent will be obtained from all participants prior to enrolment. Data will be anonymised, securely stored on encrypted servers for a minimum of 10 years, and shared only with approval from the ethics committee. Results will be disseminated through publication in peer-reviewed journals and presentation at scientific conferences. Trial registration number: ChiCTR2500112152.

Osteoarthritis (OA) is a progressive joint disorder that predominantly affects elderly and postmenopausal individuals. Current therapies offer only transient symptom relief and are associated with significant adverse effects. Mesenchymal stem cell (MSC) therapy holds promise for OA treatment, but challenges such as poor in vivo persistence and migration away from target sites hinder its clinical application. Here, we develop a bioactive, thermosensitive hydroxypropyl chitin (HPCT) hydrogel as an injectable platform to enhance MSC-based therapy. In both papain-induced early-stage and surgically induced late-stage OA models, intra-articular injections of MSCs combined with HPCT hydrogel significantly enhance therapeutic efficacy within the osteoarthritic joint environment. This bioactive, thermosensitive hydrogel is associated with attenuation of mechanical-stress-related ferroptotic signatures in chondrocytes through the establishment of a protective biomechanical microenvironment. MSCs embedded within the hydrogel adopt a spheroidal configuration, which improves their viability, enhances their anti-inflammatory properties, and prolongs their retention at the site of injury. These combined effects promote cartilage repair, regeneration, and sustained joint homeostasis. Mechanistically, these effects are accompanied by modulation of mechanotransduction-related pathways, including reduced Piezo1 expression and restoration of GPX4-associated antioxidant capacity. Our findings highlight HPCT-based tissue engineering as a promising therapeutic strategy for addressing OA pathophysiology and improving long-term clinical outcomes.

Background: General anesthesia may counteract the neuroprotective effects of S-ketamine, so previous trials may have underestimated the efficacy of S-ketamine to reduce postoperative delirium (POD). The authors hypothesized that administration of S-ketamine in a non–general anesthesia setting would reduce the risk of POD. Methods: This study was conducted at a high-volume arthroplasty referral center where standardized, evidence-based perioperative protocols are implemented with high fidelity. This study included 372 elderly patients undergoing total hip or knee arthroplasty under neuraxial anesthesia. Patients were enrolled from November 2023 to October 2024, and in-person follow-up assessments were conducted from admission to 3 days after surgery. Patients were randomized to receive either S-ketamine (n = 186) or normal saline placebo (n = 186). The primary outcome was risk of POD within 3 days after surgery. Secondary outcomes were number of POD episodes, POD onset time and duration, POD severity, POD subtype, pain score (numeric rating scale), opioid consumption, number of patients requiring rescue analgesia, sleep quality, clinical outcomes, and harms. Results: Within 3 days after surgery, 15 patients in the S-ketamine group (8.06%) developed POD, compared to 38 patients (20.43%) in the placebo group (adjusted odds ratio, 0.29; 95% CI, 0.14 to 0.63; P = 0.002). On postoperative day 1, patients in the S-ketamine group experienced significantly less pain during exercise and physical therapy and had a lower incidence of rescue analgesia use compared to the placebo group. The incidence of hallucinations, dizziness, and nightmares was higher in the S-ketamine group than in the placebo group. The incidence of other complications was low in both groups, with no statistically significant differences. Conclusions: S-ketamine can reduce risk of POD in elderly patients undergoing total hip or knee arthroplasty under neuraxial anesthesia. However, generalizability of these findings may be limited due to the study’s setting.

The primary reasons for postoperative joint prosthesis revision after total knee arthroplasty (TKA) are periprosthetic aseptic prosthesis loosening and joint infection (PJI). The objective of this study is to analyze the predominant microbial species responsible for PJI while also discussing was related. A retrospective analysis was conducted on patients who underwent TKA revision surgery for the treatment of PJI and aseptic loosening of joint prostheses at our institution. Patients with aseptic loosening of the prosthesis are group A (n = 68), and patients with PJI are group B (n = 72). The fluid obtained after ultrasonic treatment was then subjected to microbial culture. Droplet Digital PCR (ddPCR) analysis was employed for DNA detection. In our study, we included a total of 140 patients divided into groups A (patients with aseptic loosening of the prosthesis) and B (patients with PJI). The microbial culture results showed that 30 patients (45.45%) had Staphylococcus aureus infections, and 24 patients (36.36%) had methicillin-resistant Staphylococcus aureus (MRSA) infections in group B. The DNA testing results revealed that 54.41% (n = 37) of Group A patients still had microbial infections, including both Gram-positive and Gram-negative species. Notably, these patients showed negative microbial cultures but positive DNA detection. Among them, 83.78% (n = 31) had Gram-negative infections, while 16.22% (n = 6) had Gram-positive infections. In Group B, 66 patients (91.67%) had predominantly Gram-positive infections. This study innovatively employed ddPCR for DNA detection and microbiologic analysis in 140 patients undergoing revision total knee arthroplasty due to periprosthetic joint infection and aseptic loosening, showed that most patients with PJI mainly affected by infections caused by high-virulence Gram-positive microbe, especially Staphylococcus aureus and MRSA. On the other hand, patients with aseptic loosening of the prosthesis may be associated with a history of multiple low-virulence microbial infections, primarily involving Gram-negative bacteria.

Purpose To investigate the incidence of periprosthetic joint infection (PJI) in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) after primary joint arthroplasty; to analyze the optimal cut-off values of clinical serum markers C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer for the diagnosis of PJI in RA patients; and to explore their diagnostic efficacy and clinical significance. Methods Clinical data of 15,702 patients with RA (578) or OA (15,124) who underwent total joint arthroplasty from 2013 to 2021 were retrospectively analyzed. Serum CRP, ESR, and D-dimer were recorded for each patient, and subject characteristic curves were used to determine the optimal threshold values of CRP, ESR, and D-dimer for RA-PJI and OA-PJI and to compare the areas under the curves to assess the diagnostic efficacy of the optimal threshold values of serologic indices for RA-PJI. Results The five year incidence of PJI was 6.92% in RA patients and 0.67% in OA patients. The optimal thresholds of CRP, ESR, and D-dimer for the diagnosis of RA-PJI were respectively 13.85 mg/L, 33.02 mm/h, and 796.50 ng/mL. The sensitivities of the optimal thresholds were respectively 67.6%, 62.2%, and 56.8%, and the specificities were 74.7%, 60.4%, and 74.4%. Conclusion RA patients have a higher incidence of PJI than OA patients. The optimal thresholds for CRP, ESR, and d-dimer for the diagnosis of PJI were higher in RA patients than in OA patients, but the sensitivity and specificity of the diagnosis were not as good as in OA patients.