Nanfang Hospital

The role of ultrasound in small bowel stricturing Crohn's disease (CD) is unclear. We aimed to investigate whether intestinal ultrasound can be used to monitor treatment response, guide treatment strategy, and predict outcomes in small bowel stricturing CD. We performed a multicenter retrospective study of 121 consecutive patients with small bowel stricturing CD who received biological therapy for at least 3 months. Two kinds of ultrasonographic response were evaluated: inflammation response (improvement in bowel wall thickness and vascular intensity) and stricture response (inflammation response with no luminal narrowing). Treatment was optimized when no inflammation response or loss of inflammation response was detected. Cox regression analysis was performed to investigate the predictors of CD-related hospitalization. The rate of inflammation response increased from 57.0% at the end of induction therapy (date 1) to 67.8% 1 year later (date 2) (p = .031). No significant difference was observed for the rate of stricture response between date 1 and date 2 (28.1% versus 27.3%, p = 1.000). Ultrasound led to 91 treatment optimizations, after which 29 patients achieved inflammation response and 9 achieved stricture response. Multivariate analysis showed that stricture response at the end of induction therapy was independently associated with a decreased risk for CD-related hospitalization (hazard ratio 0.29, 95% CI 0.09-0.96; p = .043). Intestinal ultrasound can be used to monitor treatment response and guide treatment strategy in small bowel stricturing CD. Early stricture response on intestinal ultrasound is associated with improved outcomes.

Renal osteodystrophy (ROD), a skeletal complication of chronic kidney disease (CKD)-mineral and bone disorder, may influence perioperative outcomes after total knee arthroplasty (TKA), but its impact remains unclear. This study examined patient characteristics, hospital resource utilization, and postoperative complications in ROD patients undergoing primary TKA. We performed a retrospective cohort analysis of the National Inpatient Sample (2010-2019). Adults undergoing primary TKA were identified and stratified by ROD status. Propensity score matching (PSM; 1:20) was used to balance age, sex, race, comorbidities, and CKD stage. Outcomes included length of stay (LOS), hospital charges, and medical and surgical complications. Among 1,196,522 TKA patients, 283 (0.02%) had ROD. After matching (n = 5,337 controls), ROD patients had a longer median LOS (3 vs. 3 days; p < 0.001) and markedly higher median hospital charges ($58,550 vs. $18,004; p < 0.001). ROD was associated with increased odds of medical complications, including thrombocytopenia (OR: 3.2; 95% CI: 1.9-5.2), convulsion (OR: 6.9; 2.5-19.6), heart failure (OR: 2.3; 1.5-3.4), chest pain (OR: 3.4; 1.2-10.0), acute cerebrovascular disease (OR: 3.0; 1.4-6.4), stroke (OR: 3.3; 1.6-6.8), pneumonia (OR: 3.9; 1.7-9.0), and acute renal failure (OR: 2.3; 1.6-3.5). Surgical risks were also elevated, notably periprosthetic fracture (OR: 7.1; 2.2-22.9), joint dislocation (OR: 4.6; 1.7-12.3), and lower limb peripheral nerve injury (OR: 2.5; 1.4-4.7). ROD patients undergoing primary TKA incur greater hospital resource use and substantially higher rates of diverse medical and surgical complications. These findings highlight ROD as an independent risk factor warranting targeted preoperative risk stratification, multidisciplinary perioperative planning, and bone health optimization to improve outcomes and resource efficiency in this high-risk population. The level of evidence is 3. Trial registration is not applicable.

Heterotopic ossification (HO) within tendons leads to debilitating tissue dysfunction, primarily arising from the abnormal osteogenic differentiation of tendon-derived stem cells (TDSCs). Despite its clinical prevalence, effective pharmacological treatments remain elusive. Farnesol, a natural isoprenoid with potent anti-inflammatory properties, represents a novel but unexplored candidate for musculoskeletal repair. This study aimed to evaluate the therapeutic efficacy of Farnesol in attenuating tendon HO and to elucidate the specific molecular mechanisms driving its effects. The anti-osteogenic effects of Farnesol were assessed using invitro TDSC differentiation assays and an invivo tendon injury model. Integrated RNA sequencing and network pharmacology analysis were employed to identify potential molecular targets. The mechanism was rigorously validated through rescue experiments using a specific GSTP1 inhibitor. Farnesol treatment significantly inhibited osteogenic differentiation invitro and attenuated ectopic bone formation invivo. Mechanistic screening identified the GSTP1/MAPK signaling axis as a critical regulatory pathway. Crucially, the administration of a GSTP1 inhibitor reversed the suppressive effects of Farnesol on osteogenesis, confirming GSTP1 as the primary mediator. Farnesol effectively inhibits the progression of post-traumatic tendon HO by targeting the GSTP1/MAPK pathway. These findings provide the first evidence of Farnesol's therapeutic potential in preventing pathological ossification.

ABSTRACTChimeric antigen receptor T (CAR‐T) cells have been used to treat patients with glioblastoma (GBM) in clinical trial settings by targeting GBM‐associated antigens. However, the efficacy of these CAR‐T cells remains limited mainly due to the heterogeneous expression of tumor antigen and their anergy in the tumor microenvironment (TME). Cytokine‐inducible SH2‐containing protein (CIS, encoded by the gene CISH) is a potent intracellular checkpoint inducing T‐cell anergy. Here, we identified fibroblast activation protein alpha (FAPα) as a highly attractive target for CAR‐T cell therapy against GBM based on its dual expression pattern (on tumor cells and perivascular cells) in GBM. A panel of nanobodies specific for FAPα was isolated, and FAPα‐targeting CAR‐T cells were developed using the isolated nanobody to verify their specific cytotoxicity to GBM cells. Furthermore, a non‐viral circular single‐stranded DNA (cssDNA)‐based CRISPR/Cas9‐targeted genome‐editing (cssDNA/CRISPR/Cas9) technology was used to integrate CAR cassettes at the CISH locus to generate CISH‐knockout (CISH‐KO) CAR‐T cells. The resulting CISH‐KO‐CAR‐T cells exhibited robust proliferation and potent anti‐GBM activity in vitro and in vivo. Thus, our results provide novel engineered CAR‐T cells with enhanced efficacy against GBM.

Enterococcus faecalis is strongly associated with persistent inflammation of the periapical tissue. 4-Octyl itaconate (4-OI), a derivative of itaconate that can permeate the cell membrane, has potent immunomodulatory effects on macrophage polarisation. However, the effect of 4-OI on apical periodontitis induced by the gram-positive bacterium E. faecalis has not yet been reported. This study explored whether 4-OI could alleviate E. faecalis-induced apical periodontitis by regulating macrophage polarisation. A model of apical periodontitis was established in mice by pulp exposure and intra-radicular infection with E. faecalis. 4-OI was then administered intraperitoneally. Periapical bone destruction, periapical inflammation, and macrophage polarisation were assessed. Additionally, RAW264.7 cells were pretreated with 4-OI and exposed to heat-killed E. faecalis (HKEF) invitro. The expression of polarisation-related markers was examined. The potential role of nuclear factor E2-related factor 2 (Nrf2) signalling was also explored by detecting the expression and nuclear translocation of Nrf2. Finally, genetic and pharmacological interventions targeting Nrf2 were performed to better understand its role in the 4-OI-mediated polarisation of HKEF-stimulated RAW264.7 cells. 4-OI treatment reduced periapical bone destruction and periapical inflammation in the mouse model of E. faecalis-induced apical periodontitis. Moreover, 4-OI inhibited macrophage M1 polarisation in the periapical region and inhibited the expression of M1 polarisation-related genes in E. faecalis-infected macrophages. Mechanistically, 4-OI treatment significantly enhanced the expression and nuclear localisation of Nrf2 and its downstream target heme oxygenase-1 in E. faecalis-infected macrophages invitro. However, suppression of M1 macrophage polarisation by 4-OI was reduced following Nrf2 inhibition. 4-OI inhibits E. faecalis-induced macrophage M1 polarisation probably by activating the Nrf2 antioxidant system, thereby suppressing experimental apical periodontitis in mice. These findings suggest that 4-OI possesses great potential as a valuable adjunct to conventional root canal therapy in the management of E. faecalis-related refractory apical periodontitis.