The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Objective:To summarize the safety and efficacy of thoracoscopic minimally invasive " one-stop" ablation for the treatment of atrial fibrillation(AF).Methods:A retrospective study was conducted on all patients with isolated atrial fibrillation who underwent thoracoscopic radiofrequency ablation combined with left atrial appendage clipping(LAAC) at West China Hospital of Sichuan University from September 2019 to October 2023. Preoperative baseline data, perioperative complications, and 3-month, 6-month, and 12-month postoperative follow-up data were collected and analyzed.Results:A total of 87 patients were included, with a mean age of(60.5±9.0) years old. Among them, 47 were males and 40 were females. Of these patients, 12 had paroxysmal AF, and 75 had persistent AF. Fourteen patients had a prior history of catheter-based radiofrequency ablation, and 11 had a history of transient ischemic attack(TIA) or stroke. All procedures were successfully completed without conversion to open thoracotomy, perioperative mortality, or perioperative stroke events. During the follow-up period, one patient died, no strokes or left atrial appendage reconnection events were observed. The sinus rhythm maintenance rates at 3、6 and 12 months postoperatively were 89.6%(78/87)、82.8%(72/87) and 75.9%(66/87), respectively. Multivariate logistic regression analysis identified a preoperative left atrial anteroposterior diameter>40 mm as an independent risk factor for postoperative AF recurrence. Conclusion:Thoracoscopic minimally invasive ablation combined with left atrial appendage clipping as a " one-stop" procedure is a safe and effective method for the treatment of isolated atrial fibrillation, achieving satisfactory surgical ablation success rates while effectively preventing stroke.

Objective:To evaluate the characteristic manifestations of lumbar fusion following oblique lateral interbody fusion (OLIF), determine the specific incidence of these patterns, and the identify factors associated with fusion characteristics.Methods:This retrospective study analyzed 209 patients who underwent OLIF surgery at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, between July 2017 and September 2023. The cohort had a mean age of 64.2±9.8 years and included 125 males and 84 females. A total of 338 lumbar segments were assessed, comprising 159 segments treated with stand-alone OLIF (OLIF-SA) and 179 segments treated with OLIF combined with posterior pedicle screw fixation (OLIF-PSF). Inclusion criteria were: patients aged 18-80 years who underwent OLIF with complete radiographic records. Surgical parameters, including fixation method, number of fused segments, surgical approach, and cage dimensions (height and width), were obtained from operative records. Radiographic evaluation included preoperative osteophytes, Hounsfield unit (HU) values of endplates, and cage positioning. Fusion rate, fusion pattern (lateral vs. central), cage subsidence, and related influencing factors were assessed. Clinical outcomes were measured via the Oswestry disability index (ODI) and visual analog scale (VAS) preoperatively, immediately postoperatively, and at 1-year follow-up. Results:The overall fusion rate was 98.2% (332/338), with a non-union rate of 1.8% (6/338). The incidence of lateral fusion was 40.2% (136/338). In the OLIF-SA group, lateral and central fusion rates were 50.3% (80/159) and 49.7% (79/159), respectively, with no cases of non-union. In the OLIF-PSF group, lateral fusion occurred in 31.3% (56/179), central fusion in 65.4% (117/179), and non-union in 3.3% (6/179), with statistically significant differences between groups ( P<0.05). Preoperative osteophytes and higher endplate HU values were significantly associated with lateral fusion ( P<0.05). However, cage dimensions and cage position (anterior-posterior and lateral placement) were not significantly associated with fusion pattern ( P>0.05). Overall, 61.5% (208/338) of segments showed no cage subsidence; 24.5% (83/338) had settling, and 14.0% (47/338) had grade 1 or higher subsidence. Among lateral fusion cases, the rates of no subsidence, anchoring, grade 1, grade 2, and grade 3 subsidence were 67.6%, 21.3%, 7.4%, 3.9%, and 0.7%, respectively. In the central fusion group, these rates were 59.2%, 27.6%, 9.2%, 2.5%, and 1.3%, respectively. In the non-union group, grade 2 and 3 subsidence occurred in 50% (3/6) each, significantly higher than in the other fusion groups ( P<0.05). Post hoc analysis confirmed that grade 2 and 3 subsidence rates were significantly elevated in the non-union group compared to the lateral and central fusion groups, while other subsidence categories showed no significant differences across groups. Clinically, patients showed significant improvements in ODI and VAS scores following surgery ( P<0.05). Conclusions:Lateral fusion occurred in 40.2% of OLIF cases. The OLIF-SA technique, preoperative osteophytes, and elevated preoperative HU values were significantly associated with lateral fusion. In contrast, surgical approach, number of fused segments, cage height, width, and cage positioning did not significantly influence the occurrence of lateral fusion.

Objective:To evaluate the characteristic manifestations of lumbar fusion following oblique lateral interbody fusion (OLIF), determine the specific incidence of these patterns, and the identify factors associated with fusion characteristics.Methods:This retrospective study analyzed 209 patients who underwent OLIF surgery at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, between July 2017 and September 2023. The cohort had a mean age of 64.2±9.8 years and included 125 males and 84 females. A total of 338 lumbar segments were assessed, comprising 159 segments treated with stand-alone OLIF (OLIF-SA) and 179 segments treated with OLIF combined with posterior pedicle screw fixation (OLIF-PSF). Inclusion criteria were: patients aged 18-80 years who underwent OLIF with complete radiographic records. Surgical parameters, including fixation method, number of fused segments, surgical approach, and cage dimensions (height and width), were obtained from operative records. Radiographic evaluation included preoperative osteophytes, Hounsfield unit (HU) values of endplates, and cage positioning. Fusion rate, fusion pattern (lateral vs. central), cage subsidence, and related influencing factors were assessed. Clinical outcomes were measured via the Oswestry disability index (ODI) and visual analog scale (VAS) preoperatively, immediately postoperatively, and at 1-year follow-up. Results:The overall fusion rate was 98.2% (332/338), with a non-union rate of 1.8% (6/338). The incidence of lateral fusion was 40.2% (136/338). In the OLIF-SA group, lateral and central fusion rates were 50.3% (80/159) and 49.7% (79/159), respectively, with no cases of non-union. In the OLIF-PSF group, lateral fusion occurred in 31.3% (56/179), central fusion in 65.4% (117/179), and non-union in 3.3% (6/179), with statistically significant differences between groups ( P<0.05). Preoperative osteophytes and higher endplate HU values were significantly associated with lateral fusion ( P<0.05). However, cage dimensions and cage position (anterior-posterior and lateral placement) were not significantly associated with fusion pattern ( P>0.05). Overall, 61.5% (208/338) of segments showed no cage subsidence; 24.5% (83/338) had settling, and 14.0% (47/338) had grade 1 or higher subsidence. Among lateral fusion cases, the rates of no subsidence, anchoring, grade 1, grade 2, and grade 3 subsidence were 67.6%, 21.3%, 7.4%, 3.9%, and 0.7%, respectively. In the central fusion group, these rates were 59.2%, 27.6%, 9.2%, 2.5%, and 1.3%, respectively. In the non-union group, grade 2 and 3 subsidence occurred in 50% (3/6) each, significantly higher than in the other fusion groups ( P<0.05). Post hoc analysis confirmed that grade 2 and 3 subsidence rates were significantly elevated in the non-union group compared to the lateral and central fusion groups, while other subsidence categories showed no significant differences across groups. Clinically, patients showed significant improvements in ODI and VAS scores following surgery ( P<0.05). Conclusions:Lateral fusion occurred in 40.2% of OLIF cases. The OLIF-SA technique, preoperative osteophytes, and elevated preoperative HU values were significantly associated with lateral fusion. In contrast, surgical approach, number of fused segments, cage height, width, and cage positioning did not significantly influence the occurrence of lateral fusion.

Objective:To summarize the safety and efficacy of thoracoscopic minimally invasive " one-stop" ablation for the treatment of atrial fibrillation(AF).Methods:A retrospective study was conducted on all patients with isolated atrial fibrillation who underwent thoracoscopic radiofrequency ablation combined with left atrial appendage clipping(LAAC) at West China Hospital of Sichuan University from September 2019 to October 2023. Preoperative baseline data, perioperative complications, and 3-month, 6-month, and 12-month postoperative follow-up data were collected and analyzed.Results:A total of 87 patients were included, with a mean age of(60.5±9.0) years old. Among them, 47 were males and 40 were females. Of these patients, 12 had paroxysmal AF, and 75 had persistent AF. Fourteen patients had a prior history of catheter-based radiofrequency ablation, and 11 had a history of transient ischemic attack(TIA) or stroke. All procedures were successfully completed without conversion to open thoracotomy, perioperative mortality, or perioperative stroke events. During the follow-up period, one patient died, no strokes or left atrial appendage reconnection events were observed. The sinus rhythm maintenance rates at 3、6 and 12 months postoperatively were 89.6%(78/87)、82.8%(72/87) and 75.9%(66/87), respectively. Multivariate logistic regression analysis identified a preoperative left atrial anteroposterior diameter>40 mm as an independent risk factor for postoperative AF recurrence. Conclusion:Thoracoscopic minimally invasive ablation combined with left atrial appendage clipping as a " one-stop" procedure is a safe and effective method for the treatment of isolated atrial fibrillation, achieving satisfactory surgical ablation success rates while effectively preventing stroke.

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Humans ; Perinatology ; Delivery of Health Care

Objective     To recognize the different phases of Korotkoff sounds through deep learning technology, so as to improve the accuracy of blood pressure measurement in different populations. Methods     A classification model of the Korotkoff sounds phases was designed, which fused attention mechanism (Attention), residual network (ResNet) and bidirectional long short-term memory (BiLSTM). First, a single Korotkoff sound signal was extracted from the whole Korotkoff sounds signals beat by beat, and each Korotkoff sound signal was converted into a Mel spectrogram. Then, the local feature extraction of Mel spectrogram was processed by using the Attention mechanism and ResNet network, and BiLSTM network was used to deal with the temporal relations between features, and full-connection layer network was applied in reducing the dimension of features. Finally, the classification was completed by SoftMax function. The dataset used in this study was collected from 44 volunteers (24 females, 20 males with an average age of 36 years), and the model performance was verified using 10-fold cross-validation. Results     The classification accuracy of the established model for the 5 types of Korotkoff sounds phases was 93.4%, which was higher than that of other models. Conclusion     This study proves that the deep learning method can accurately classify Korotkoff sounds phases, which lays a strong technical foundation for the subsequent design of automatic blood pressure measurement methods based on the classification of the Korotkoff sounds phases.