Synergistic Potential of Nanomedicine in Prostate Cancer Immunotherapy: Breakthroughs and Prospects.

Given the global prevalence of prostate cancer in men, it is crucial to explore more effective treatment strategies. Recently, immunotherapy has emerged as a promising cancer treatment due to its unique mechanism of action and potential long-term effectiveness. However, its limited efficacy in prostate cancer has prompted renewed interest in developing strategies to improve immunotherapy outcomes. Nanomedicine offers a novel perspective on cancer treatment with its unique size effects and surface properties. By employing targeted delivery, controlled release, and enhanced immunogenicity, nanoparticles can be synergized with nanomedicine platforms to amplify the effectiveness of immunotherapy in treating prostate cancer. Simultaneously, nanotechnology can address the limitations of immunotherapy and the challenges of immune escape and tumor microenvironment regulation. Additionally, the synergistic effects of combining nanomedicine with other therapies offer promising clinical outcomes. Innovative applications of nanomedicine include smart nanocarriers, stimulus-responsive systems, and precision medicine approaches to overcome translational obstacles in prostate cancer immunotherapy. This review highlights the transformative potential of nanomedicine in enhancing prostate cancer immunotherapy and emphasizes the need for interdisciplinary collaboration to drive research and clinical applications forward.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for initially unresectable locally advanced colon cancer: short-term outcomes of an open-label, single-centre, randomised, controlled, phase 3 trial.

Background: Neoadjuvant chemotherapy (NACT) is commonly used to downstage the tumor in locally advanced colon cancer (LACC) and improve the R0 resection rate. Neoadjuvant chemoradiotherapy (NACRT) is the standard treatment for locally advanced rectal and esophageal cancers, but its benefits in LACC remain poorly understood. This study aimed to compare the effects and safety of NACRT and NACT on R0 resection and survival rates in initially unresectable LACC. Methods: This was an open-label, single-center, randomized, controlled trial conducted between May 11, 2019 and May 30, 2022. Forty-five patients with initially unresectable LACC were randomly allocated to the NACT (control, n = 20) or NACRT (research, n = 25) group. The NACT group received XELOX (oxaliplatin 100-130 mg/m2, qd, d1, every 3 weeks; and capecitabine 1000 mg/m2, bid, d1-d14, every 3 weeks) for 4 cycles. The NACRT group, in addition to chemotherapy, received daily irradiation (GTV 45-50 Gy/25 F; CTV 42.5-45 Gy/25 F). Surgery was scheduled 6-12 weeks after neoadjuvant treatment and adjuvant chemotherapy was administered if the patient developed resectable LACC. The primary endpoint was the 5-year overall survival (OS) rate. The secondary outcomes included the 3-year progression-free survival (PFS) and R0 resection rates. This study was registered with ClinicalTrials.gov (NCT03970694). Findings: In short-term outcome analysis, NACRT significantly improved the R0 resection rate (80% for NACRT vs. 20% for NACT, P < 0.001). The NACRT and NACT groups had a 3-year OS of 87.6% and 75% (P = 0.037) and a 3-year PFS of 76% and 45% (P = 0.049), respectively. The 5-year OS was not reached. In the NACRT group, no local or regional recurrence was observed in patients who underwent surgery during the follow-up period, compared to two patients in the NACT group. Both NACT and NACRT were well tolerated, with no significant differences in severe adverse events. The most commonly observed grade 3-4 AE was myelosuppression (39% for NACRT and 47% for NACT, P = 0.609). No grade 5 AEs were observed between the two groups. Interpretation: Adding radiation to NACT increased the R0 resection rate, prolonged the PFS, and potentially improved OS in selected patients with initially unresectable LACC. The trial findings indicate that this approach is safe, feasible, and may confer a survival benefit. Funding: This study was supported by grants from the National Natural Science Foundation of China (82373213 to Dr Gao, 82202952 to Dr Wang); and the Natural Science Foundation of Guangdong Province (2023A1515010290 to Dr Chang). Funding sources were not involved in the study design, data collection, analysis and interpretation, writing of the report, or decision to submit the article for publication.

A comparative study of the effect of facet tropism on the index-level kinematics and biomechanics after artificial cervical disc replacement (ACDR) with Prestige LP, Prodisc-C vivo, and Mobi-C: a finite element study.

INTRODUCTION: Artificial cervical disc replacement (ACDR) is a widely accepted surgical procedure in the treatment of cervical radiculopathy and myelopathy. However, some research suggests that ACDR may redistribute more load onto the facet joints, potentially leading to postoperative axial pain in certain patients. Earlier studies have indicated that facet tropism is prevalent in the lower cervical spine and can significantly increase facet joint pressure. The present study aims to investigate the changes in the biomechanical environment of the cervical spine after ACDR using different prosthese when facet tropism is present. METHODS: A C2-C7 cervical spine finite element model was created. Symmetrical, moderate asymmetrical (7 degrees tropism), and severe asymmetrical (14 degrees tropism) models were created at the C5/C6 level by adjusting the left-side facet. C5/C6 ACDR with Prestige LP, Prodisc-C vivo, and Mobi-C were simulated in all models. A 75 N follower load and 1 N⋅m moment was applied to initiate flexion, extension, lateral bending, and axial rotation, and the range of motions (ROMs), facet contact forces(FCFs), and facet capsule stress were recorded. RESULTS: In the presence of facet tropism, all ACDR models exhibited significantly higher FCFs and facet capsule stress compared to the intact model. In the asymmetric model, FCFs on the right side were significantly increased in neutral position, extension, left bending and right rotation, and on both sides in right bending and left rotation compared to the symmetric model. All ACDR model in the presence of facet tropism, exhibited significantly higher facet capsule stresses at all positions compared to the symmetric model. The stress distribution on the facet surface and the capsule ligament in the asymmetrical models was different from that in the symmetrical model. CONCLUSIONS: The existence of facet tropism could considerably increase FCFs and facet capsule stress after ACDR with Prestige-LP, Prodisc-C Vivo, and Mobi-C. None of the three different designs of implants were able to effectively protect the facet joints in the presence of facet tropism. Research into designing new implants may be needed to improve this situation. Clinical trials are needed to validate the impact of facet tropism.

Application of three-dimensional (3D) magnetic resonance (MR) Multi-Echo iN Steady-state Acquisition sequences in preoperative evaluation of lumbar disc herniation: a prospective study.

Background: Conventional spinal magnetic resonance imaging (MRI) cannot provide accurate diagnosis and surgical planning; thin-layer scanning can enhance the diagnostic efficacy. This study aimed to investigate the value of 3-dimensional (3D) magnetic resonance (MR) in preoperative evaluation of lumbar disc herniation, with a focus on the application of Multi-Echo iN Steady-state Acquisition (MENSA) sequence. Methods: A total of 51 patients who underwent lumbar disc herniation surgery in West China Hospital of Sichuan University from June 2021 to December 2021 were prospectively enrolled. A cross-sectional study was conducted on those patients. The Cube group was scanned using 3D-FSE-Cube sequence, the Cube stir group was scanned using 3D-FSE-Cube Short Tau Inversion Recovery (STIR) sequence, and the MENSA group was scanned using MENSA sequence. Signal and noise values of nerve, herniated disc, ligamentum flavum (LF), and soft tissue were measured on the 3 groups. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Objective scores were calculated by analysis of variance (ANOVA). Image quality was scored by a 5-point method. Friedman test was used to compare subjective scores, and Kappa test was used to evaluate the consistency of 2 readers' scores. Results: The nerve root SNRs in the MENSA and Cube stir groups were higher than that in the Cube group (P<0.01), but there was no substantial statistical difference between the 2 groups. The herniated disc and LF SNRs of the MENSA group were greater than those of the Cube stir and Cube groups (P<0.01). Soft tissue SNR was greater in the MENSA group compared with the Cube stir group (P<0.01), which was greater than the SNR in the Cube group (P<0.01). The nerve root CNR of the Cube group (102.88±73.19) was greater than that of the MENSA group (55.98±25.26, P<0.01), which was higher than the CNR in the Cube Stir group (29.42±16.22, P<0.01). The herniated disc CNR was higher in the MENSA and Cube groups than that in the Cube Stir group. The CNR of LF was greater in the MENSA group (37.71±16.87) compared to the Cube group (29.76±25.73, P=0.03), which was greater than that in the Cube stir group (10.50±7.75, P<0.01). Among the subjective ratings of 2 reviewers, MENSA sequence scored highest in the qualitative measures of image quality. In the consistency test, the Kappa values of 2 readers for 3 groups of images were all greater than 0.73, indicating good consistency. The differences of subjective scores among all groups were statistically significant (P<0.05). Overall, it was indicated that the consistency test results of the 2 readers were statistically significant and consistent. The MENSA group had the highest accuracy in diagnosing nerve compression. In addition, MENSA sequence ranked highest among the 3 sequences with 94.1% diagnostic accuracy. Conclusions: The preoperative 3D MRI MENSA sequence can clearly depict the nerve roots and offer desirable contrast between the nerve roots, LF, bone, and intervertebral discs (IVDs). Patients with lumbar degeneration can effectively benefit from MENSA sequence since it provides useful imaging information to help understand disc herniation and compression of adjacent tissues when developing preoperative surgical strategies.

Combined effect of artificial cervical disc replacement and facet tropism on the index-level facet joints: a finite element study.

BACKGROUND: Artificial Cervical Disc Replacement (ACDR) is an effective treatment for cervical degenerative disc diseases. However, clinical information regarding the facet joint alterations after ACDR was limited. Facet tropism is common in the sub-axial cervical spine. Our previous research indicated that facet tropism could lead to increased pressure on the cervical facet joints. This study aimed to assess the impact of facet tropism on the facet contact force and facet capsule stress after ACDR. METHODS: A C2-T1 cervical finite element model was constructed from computed tomography (CT) scans of a 28-year-old male volunteer. Symmetrical, moderate asymmetrical (7 degrees tropism), and severe asymmetrical (14 degrees tropism) models were created at the C5/C6 level by altering the facet orientation at the C5-C6 level. The C5/C6 ACDR was simulated in the intact, moderate asymmetrical and severe asymmetrical models. A 75-N follower load with 1.0-Nm moments was applied to the top of C2 vertebra in the models to simulate flexion, extension, lateral bending, and axial rotation with the T1 vertebra fixed. The range of motions (ROMs) under all moments, facet contact forces (FCFs) and facet capsule strains were tested. RESULTS: In the asymmetrical model, the right FCFs considerably increased under flexion, extension, right bending, left rotation, especially under right bending the right sided FCF of the severe asymmetrical model was about 5.44 times of the neutral position, and 3.14 times of the symmetrical model. and concentrated on the cephalad part of the facets. The facet capsule stresses on both sides remarkably increased under extension, lateral bending and right rotation. In the moderate and severe asymmetrical models, the capsule strain was greater on both sides of each position than in the symmetric model. CONCLUSIONS: The face tropism increased facet contact force and facet capsule strain after ACDR, especially under extension, lateral bending, and rotation, and also could result in abnormal stress distribution on the facet joint surface and facet joint capsule. The results suggest that face tropism might be a risk factor for post-operative facet joint degeneration progression after ACDR. Facet tropism may be noteworthy when ACDR is considered as a surgical option.

Excessive hydrogen sulfide-induced activation of NMDA receptors in the colon participates in anxiety- and compulsive-like behaviors in a rodent model of hemorrhagic shock and resuscitation.

OBJECTIVE: Hemorrhagic shock and resuscitation (HSR) cause inflammatory responses in the gastrointestinal tract and is associated with substantial morbidity and mortality rates. Hydrogen sulfide (H2S), a gasotransmitter with pleiotropic activity, exhibits anti-inflammatory benefits at physiological levels. However, deleterious effects are observed when its concentration increases. In this investigation, we employed a mouse model of HSR to examine the effects of an H2S scavenger on the gastrointestinal tract and brain, with emphasis on N-Methyl-d-Aspartate (NMDA) receptor function. METHODS: Mice were immediately administered dl-propargylglycine (PAG) intragastrically as an H2S scavenger after HSR exposure. The O-maze and buried beads tests were used to assess compulsive- and anxiety-like behaviors. Pathological changes in the intestine were evaluated at 24 and 30 days after HSR. Subsequently, at 30 days after HSR, we examined electrophysiological and pathological changes in the amygdala. RESULTS: Within 24 h of HSR exposure, animals treated with PAG showed significantly lower colonic injury. Additionally, compared to the HSR-treated mice 30 days after HSR, the PAG-treated mice displayed reduced buried beads, increased open-arm time, lower blood levels of Diamine Oxidase (DAO) and considerably improved ZO-1 intensity, a stronger association between the delta rhythm phase and beta activity amplitude, and lower neuroinflammatory response in the amygdala. MK-801, an NMDA receptor inhibitor, significantly reversed H2S-induced intestinal and cerebral injury. CONCLUSION: This experimental data suggests that H2S-induced excessive activation of NMDA receptors contributes to anxiety- and compulsive-like behaviors caused by HSR.

Detection Method of Stator Coating Quality of Flat Wire Motor Based on Improved YOLOv8s.

The stator of a flat wire motor is the core component of new energy vehicles. However, detecting quality defects in the coating process in real-time is a challenge. Moreover, the number of defects is large, and the pixels of a single defect are very few, which make it difficult to distinguish the defect features and make accurate detection more difficult. To solve this problem, this article proposes the YOLOv8s-DFJA network. The network is based on YOLOv8s, which uses DSFI-HEAD to replace the original detection head, realizing task alignment. It enhances joint features between the classification task and localization task and improves the ability of network detection. The LEFG module replaces the C2f module in the backbone of the YOLOv8s network that reduces the redundant parameters brought by the traditional BottleNeck structure. It also enhances the feature extraction and gradient flow ability to achieve the lightweight of the network. For this research, we produced our own dataset of stator coating quality regarding flat wire motors. Data augmentation technology (Gaussian noise, adjusting brightness, etc.) enriches the dataset, to a certain extent, which improves the robustness and generalization ability of YOLOv8s-DFJA. The experimental results show that in the performance of YOLOv8s-DFJA compared with YOLOv8s, the mAP@.5 index increased by 6.4%, the precision index increased by 1.1%, the recall index increased by 8.1%, the FPS index increased by 9.8FPS/s, and the parameters decreased by 3 Mb. Therefore, YOLOv8s-DFJA can be better realize the fast and accurate detection of the stator coating quality of flat wire motors.

Delivery of miRNAs Using Nanoparticles for the Treatment of Osteosarcoma.

Osteosarcoma is the predominant primary malignant bone tumor that poses a significant global health challenge. MicroRNAs (miRNAs) that regulate gene expression are associated with osteosarcoma pathogenesis. Thus, miRNAs are potential therapeutic targets for osteosarcoma. Nanoparticles, widely used for targeted drug delivery, facilitate miRNA-based osteosarcoma treatment. Numerous studies have focused on miRNA delivery using nanoparticles to inhibit the progress of osteosarcoma. Polymer-based, lipid-based, inorganic-based nanoparticles and extracellular vesicles were used to deliver miRNAs for the treatment of osteosarcoma. They can be modified to enhance drug loading and delivery capabilities. Also, miRNA delivery was combined with traditional therapies, for example chemotherapy, to treat osteosarcoma. Consequently, miRNA delivery offers promising therapeutic avenues for osteosarcoma, providing renewed hope for patients. This review emphasizes the studies utilizing nanoparticles for miRNA delivery in osteosarcoma treatment, then introduced and summarized the nanoparticles in detail. And it also discusses the prospects for clinical applications.

An Oxidative Stress-Related Prognostic Signature Predicts Treatment Response and Outcomes for Hepatocellular Carcinoma After Transarterial Chemoembolization.

Purpose: Oxidative stress plays a critical role in promoting tumor resistance to hypoxia and chemotherapeutic drugs. However, the prognostic role of oxidative stress-related genes (OSRGs) in hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) has not been fully explored. Methods: We used transcriptome data from the GSE104580 cohort containing patients marked as responders or nonresponders to TACE therapy to identify differentially expressed OSRGs associated with TACE response (TR-OSRGs). We created a TR-OSRG prognostic signature based on TR-OSRGs using least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses in a training cohort of patients with HCC (TCGA-LIHC). We verified this prognostic signature in two external cohorts of patients who received TACE for HCC (GSE14520-TACE and ZS-TACE-37). Finally, we constructed a prognostic nomogram model for predicting survival probability of patients with HCC based on Cox regression analysis. Results: The TR-OSRG prognostic signature was created and shown to be a robust independent prognostic factor for treatment response and outcomes for HCC after TACE therapy. Risk scores based on this signature correlated with tumor stage and grade. Tumor samples from patients with higher risk scores exhibited more infiltration of immune cells and significantly increased expression of immune checkpoint genes. We also developed a nomogram for patients with HCC based on the TR-OSRG prognostic signature and clinical parameters; this nomogram was a useful quantitative analysis tool for predicting patient survival. Conclusion: The TR-OSRGs signature exhibited good performance in predicting treatment response and outcomes in patients with HCC treated with TACE.

Comparison of Titanium Mesh Cage, Nano-Hydroxyapatite/Polyamide Cage, and 3D-Printed Vertebral Body for Anterior Cervical Corpectomy and Fusion.

STUDY DESIGN: A prospective non-randomized controlled study. OBJECTIVE: To compare the clinical and radiographic outcomes of anterior cervical corpectomy and fusion (ACCF) using titanium mesh cages (TMC), nanohydroxyapatite/polyamide66 (n-HA/PA66) cages, and 3D-printed vertebral bodies (3d-VBs). SUMMARY OF BACKGROUND DATA: Postoperative subsidence of TMCs in ACCF had been widely reported. Newer implants such as n-HA/PA66 cages and 3d-VBs using biocompatible titanium alloy powder (Ti6Al4V) had been introduced to address this issue, but their outcomes remain controversial. METHODS: We enrolled 60 patients undergoing ACCF using TMCs, n-HA/PA66 cages, or 3d-VBs from January 2020 to November 2021. For each group, there were 20 patients. Follow-up was conducted for minimum two years. Clinical outcomes, including Japanese Orthopaedic Associationscores (JOA), Neck Disability Index (NDI) and Visual Analogue Scale (VAS) scores and radiographic outcomes, including FSU height, fusion rate, and cervical alignment were collected pre-operatively and at each follow-up. A loss of FSU height equal or greater than 3 mm was deemed implant subsidence. One-way analysis of variance was used for comparisons of mean values at different time points within the same group, with pairwise comparisons performed using the LSD method. The Mann-Whitney test was used for comparisons between groups. Categorical data such as gender, smoking status, implant subsidence and pathology level were analyzed using the chi-square test. RESULTS: Postoperative function of spinal unit (FSU) height loss at 2 years differed significantly among the TMC, n-HA/PA66, and 3d-VB groups, measuring 3.07±1.25 mm, 2.11±0.73 mm, and 1.46±0.71 mm, respectively (P<0.001). The rates of implant subsidence were 45%, 20%, and 10%, respectively (P=0.031). All patients obtained solid fusion at 2-year follow-up. We observed statistically significant differences in VAS and JOA scores at 3 months postoperatively, and JOA scores at 2 years postoperatively among the three groups. At two-year follow-up, the n-HA/PA66 and the 3d-VBs groups exhibited less FSU height loss, lower subsidence rates and demonstrated better cervical lordosis than the TMC group. No severe postoperative complications were observed in any of the patients, and no patient required reoperation. CONCLUSION: At two-year follow-up after ACCF, the n-HA/PA66 and the 3d-VBs groups exhibited less FSU height loss, lower subsidence rates and demonstrated better cervical lordosis than the TMC group. Longer term observation of implant subsidence in ACCF using TMC, n-HA/PA66, and 3d-VB, is necessary. LEVEL OF EVIDENCE: Therapeutic Level III.

Research on a Train Safety Driving Method Based on Fusion of an Incremental Clustering Algorithm and Lightweight Shared Convolution.

This paper addresses the challenge of detecting unknown or unforeseen obstacles in railway track transportation, proposing an innovative detection strategy that integrates an incremental clustering algorithm with lightweight segmentation techniques. In the detection phase, the paper innovatively employs the incremental clustering algorithm as a core method, combined with dilation and erosion theories, to expand the boundaries of point cloud clusters, merging adjacent point cloud elements into unified clusters. This method effectively identifies and connects spatially adjacent point cloud clusters while efficiently eliminating noise from target object point clouds, thereby achieving more precise recognition of unknown obstacles on the track. Furthermore, the effective integration of this algorithm with lightweight shared convolutional semantic segmentation algorithms enables accurate localization of obstacles. Experimental results using two combined public datasets demonstrate that the obstacle detection average recall rate of the proposed method reaches 90.3%, significantly enhancing system reliability. These findings indicate that the proposed detection strategy effectively improves the accuracy and real-time performance of obstacle recognition, thereby presenting important practical application value for ensuring the safe operation of railway tracks.

Tunable multicolor supramolecular assemblies based on phosphorescence cascade energy transfer for photocatalytic organic conversion and anti-counterfeiting.

Making full use of the captured energy by phosphorescence light-harvesting systems (PLHSs) and the tunable photoluminescence in energy transfer process to realize the multiple applications is still the challenge of PLHSs research. In this study, we have successfully constructed a highly effective PLHS with tunable multicolor luminescence and efficient conversion of photosensitizer types, which can further be used in photocatalytic organic conversion, information anti-counterfeiting and storage. The supramolecular polymer of BDBP-CB[8], which is generated by cucurbit[8]uril (CB[8]) and 4-(4-bromophenyl)-pyridine derivative (BDBP), realizes a phosphorescence emission and a change in luminescence color. Notably, white light emission was achieved and the logic gate systems were constructed utilizing the application of adjustable luminescence color. More interestingly, PLHS can be constructed by employing BDBP-CB[8] as energy donors, Sulforhodamine 101 (SR101) and Cyanine5 (Cy5) as energy acceptors, which results in a remarkably tunable multicolor photoluminescence to achieve the information storage. Furthermore, we have also found that BDBP-CB[8] can serve as type II photosensitizer for the effective production of singlet oxygen (1O2) during the photooxidation process of styrene in aqueous environments, attaining a remarkable output rate reaching as high as 89 %. Particularly, compared with 1O2 produced by type II photosensitizer BDBP-CB[8], the construction of PLHS can effectively convert type II photosensitizer to type I photosensitizer and efficiently generate superoxide anion radical (O2•-), which can be used for photocatalytic cross-dehydrogenative coupling (CDC) reaction in the aqueous solution with a yield of 90 %. Thus, we have created a PLHS that not only achieves tunable multicolor emission for information anti-counterfeiting and storage, but also realizes the conversion of reactive oxygen species (ROS) for different types photocatalytic oxidation reactions.

ECM-Mimicking Strontium-Doped Nanofibrous Microspheres for Periodontal Tissue Regeneration in Osteoporosis.

Regenerating periodontal defects in osteoporosis patients presents a significant clinical challenge. Unlike the relatively straightforward regeneration of homogeneous bone tissue, periodontal regeneration requires the intricate reconstruction of the cementum-periodontal ligament-alveolar bone interface. Strontium (Sr)-doped biomaterials have been extensively utilized in bone tissue engineering due to their remarkable pro-osteogenic attributes. However, their application in periodontal tissue regeneration has been scarcely explored. In this study, we synthesized an innovative injectable Sr-BGN/GNM scaffold by integrating Sr-doped bioactive glass nanospheres (Sr-BGNs) into the nanofiber architecture of gelatin nanofiber microspheres (GNMs). This design, mimicking the natural bone extracellular matrix (ECM), enhanced the scaffold's mechanical properties and effectively controlled the sustained release of Sr ions (Sr2+), thereby promoting the proliferation, osteogenic differentiation, and ECM secretion of PDLSCs and BMSCs, as well as enhancing vascularization in endothelial cells. In vivo experiments further indicated that the Sr-BGNs/GNMs significantly promoted osteogenesis and angiogenesis. Moreover, the scaffold's tunable degradation kinetics optimized the prolonged release and pro-regenerative effects of Sr2+ in vivo, matching the pace of periodontal regeneration and thereby facilitating the regeneration of functional periodontal tissues under osteoporotic conditions. Therefore, Sr-BGNs/GNMs emerge as a promising candidate for advancing periodontal regeneration strategies.

A near-resonant excitation strategy to achieve ultra-low threshold GaN polariton lasing.

A near-resonant excitation strategy is proposed and implemented in a 4-µm-thick GaN microcavity to realize an exciton-polariton condensate/lasing with low threshold. Strong exciton-photon coupling is demonstrated, and polariton lasing is realized with an ultra-low threshold excitation power density of about 13.3 W/cm2 at room temperature. Such an ultra-low threshold is ascribed to the implementation of the near-resonant optical excitation strategy, which enables acceleration of the exciton and polariton relaxation and suppression of the heat generation in the cavity, thereby reducing the energy loss and enhance the cavity excitation efficiency.

Evaluating the effectiveness of early urethral catheter removal combined with intermittent catheterization for promoting early recovery of bladder function after laparoscopic radical hysterectomy: a study protocol for a randomized controlled trial.

BACKGROUND: Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to nerve damage, severely impacting their postoperative quality of life. The challenges to recovery include insufficient pelvic floor muscle training and the negative effects of prolonged postoperative indwelling urinary catheters. Intermittent catheterization represents the gold standard for neurogenic bladder management, facilitating bladder training, which is an important behavioral therapy aiming to enhance bladder function through the training of the external urethral sphincter and promoting the recovery of the micturition reflex. Nevertheless, gaps remain in current research regarding optimal timing for intermittent catheterization and the evaluation of subjective symptoms of bladder dysfunction. METHODS: Cervical cancer patients undergoing laparoscopic radical hysterectomy will be recruited to this randomized controlled trial. Participants will be randomly assigned to either early postoperative catheter removal combined with intermittent catheterization group or a control group receiving standard care with indwelling urinary catheters. All these patients will be followed for 3 months after surgery. The study's primary endpoint is the comparison of bladder function recovery rates (defined as achieving a Bladder Function Recovery Grade of II or higher) 2 weeks post-surgery. Secondary endpoints include the incidence of urinary tract infections, and changes in urodynamic parameters, and Mesure Du Handicap Urinaire scores within 1 month postoperatively. All analysis will adhere to the intention-to-treat principle. DISCUSSION: The findings from this trial are expected to refine clinical management strategies for enhancing postoperative recovery among cervical cancer patients undergoing radical hysterectomy. By providing robust evidence, this study aims to support patients and their families in informed decision-making regarding postoperative bladder management, potentially reducing the incidence of urinary complications and improving overall quality of life post-surgery. TRIAL REGISTRATION: ChiCTR2200064041, registered on 24th September, 2022.

Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study.

BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Accuracy of 12 Intraocular Lens Power Formulas After Corneal Myopic Refractive Surgery.

PURPOSE: To assess the predictive accuracy of new-generation online intraocular lens (IOL) power formulas in eyes with previous myopic laser refractive surgery (LRS) and to evaluate the influence of corneal asphericity on the predictive accuracy. METHODS: The authors retrospectively evaluated 52 patients (78 eyes) with a history of laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) who subsequently underwent cataract surgery. Refractive prediction errors were calculated for 12 no-history new online formulas: 8 formulas with post-LRS versions (Barrett True-K, EVO 2.0, Hoffer QST, and Pearl DGS) using keratometry and posterior/total keratometry measured by IOLMaster 700 and 4 formulas without post-LRS versions (Cooke K6 and Kane) using keratometry and total keratometry. The refractive prediction error, mean absolute error (MAE), and percentages of eyes with prediction errors of ±0.25, ±0.50, ±0.75, ±1.00, and ±1.50 diopters (D) were compared. RESULTS: The MAEs of the 12 formulas were significantly different (F = 83.66, P < .001). The MAEs ranged from 0.62 to 0.94 D and from 1.07 to 1.84 D in the formulas with and without post-LRS versions, respectively. The EVO formula produced the lowest MAE (0.60) and MedAE (0.47), followed by the Barrett True-K (0.69 and 0.50, respectively). Each percentage of eyes with refractive prediction error was also significantly different among the 12 formulas (P < .001). CONCLUSIONS: The EVO and Barrett True-K formulas demonstrate comparable performance to the other existing formulas in eyes with a history of myopic LASIK/PRK. Surgeons should use these formulas with post-LRS versions and input keratometric values whenever possible. [J Refract Surg. 2024;40(6):e354-e361.].

Biomechanical Effects on the Prostheses and Vertebrae of Three-Level Hybrid Surgery: A Finite Element Study.

PURPOSE: Three-level hybrid surgery (HS) consisting of cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) has been partly used for the treatment of multi-level cervical degenerative disc disease (CDDD). The complications related to the implants and the collapse of the surgical vertebral bodies had been reported in multi-level anterior cervical spine surgery. Thus, this study aimed to explore the biomechanical effects on the prostheses and vertebrae in three-level HS. METHODS: A FE model of cervical spine (C0-T1) was constructed. Five surgical models were developed. They were FAF model (ACDF-CDA-ACDF), AFA model (CDA-ACDF-CDA), FFF model (three-level ACDF), SF model (single-level ACDF), and SA model (single-level CDA). A 75-N follower load and 1.0-N·m moment was applied to produce flexion, extension, lateral bending, and axial rotation. RESULTS: Compared with the intact model, the range of motion (ROM) of total cervical spine in FAF model decreased by 34.54%, 54.48%, 31.76%, and 27.14%, respectively, in flexion, extension, lateral bending, and axial rotation, which were lower than those in FFF model and higher than those in AFA model. The ROMs of CDA segments in FAF and AFA models were similar to the intact model and SA model. Compared with the intact model, the ROMs at C3/4 segment in FFF model increased from 5.71% to 7.85%, and increased from 5.31% to 6.81% at C7/T1 segment, following by FAF model, then the FAF model. The maximum interface pressures of the Prestige-LP in FAF model were similar to SA model, however the corresponding values were increased in AFA model. The maximum interface pressures of the Zero-P were increased in FAF and AFA model compared with those in SF and FFF models. The stress was mainly distributed on the screws. In AFA model, the maximum pressures of the ball and trough articulation in superior and inferior Prestige-LP were all increased compared with those in SA and FAF model. In FFF model, the maximum pressures of the vertebrae were higher than those in other models. The stress was mainly distributed on the anterior area of the vertebral bodies. CONCLUSIONS: HS seemed to be more suitable than ACDF for the surgical treatment of three-level CDDD in consideration of the biomechanical effects, especially for the two-level CDA and one-level ACDF construct. But a more appropriate CDA prosthesis should be explored in the future.

Application of artificial intelligence in the diagnosis and treatment of cardiac arrhythmia.

The rapid growth in computational power, sensor technology, and wearable devices has provided a solid foundation for all aspects of cardiac arrhythmia care. Artificial intelligence (AI) has been instrumental in bringing about significant changes in the prevention, risk assessment, diagnosis, and treatment of arrhythmia. This review examines the current state of AI in the diagnosis and treatment of atrial fibrillation, supraventricular arrhythmia, ventricular arrhythmia, hereditary channelopathies, and cardiac pacing. Furthermore, ChatGPT, which has gained attention recently, is addressed in this paper along with its potential applications in the field of arrhythmia. Additionally, the accuracy of arrhythmia diagnosis can be improved by identifying electrode misplacement or erroneous swapping of electrode position using AI. Remote monitoring has expanded greatly due to the emergence of contactless monitoring technology as wearable devices continue to develop and flourish. Parallel advances in AI computing power, ChatGPT, availability of large data sets, and more have greatly expanded applications in arrhythmia diagnosis, risk assessment, and treatment. More precise algorithms based on big data, personalized risk assessment, telemedicine and mobile health, smart hardware and wearables, and the exploration of rare or complex types of arrhythmia are the future direction.

Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in patients with type 2 diabetes at different stages of diabetic retinopathy.

AIM: To investigate systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) levels in patients with type 2 diabetes at different stages of diabetic retinopathy (DR). METHODS: This retrospective study included 141 patients with type 2 diabetes mellitus (DM): 45 without diabetic retinopathy (NDR), 47 with non-proliferative diabetic retinopathy (NPDR), and 49 with proliferative diabetic retinopathy (PDR). Complete blood counts were obtained, and NLR, PLR, and SII were calculated. The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic (ROC) curves. The relationships between DR stages and SII, PLR, and NLP were assessed using multivariate logistic regression. RESULTS: The average NLR, PLR, and SII were higher in the PDR group than in the NPDR group (P=0.011, 0.043, 0.009, respectively); higher in the NPDR group than in the NDR group (P<0.001 for all); and higher in the PDR group than in the NDR group (P<0.001 for all). In the ROC curve analysis, the NLR, PLR, and SII were significant predictors of DR (P<0.001 for all). The highest area under the curve (AUC) was for the PLR (0.929 for PLR, 0.925 for SII, and 0.821 for NLR). Multivariate regression analysis indicated that NLR, PLR, and SII were statistically significantly positive and independent predictors for the DR stages in patients with DM [odds ratio (OR)=1.122, 95% confidence interval (CI): 0.200-2.043, P<0.05; OR=0.038, 95%CI: 0.018-0.058, P<0.05; OR=0.007, 95%CI: 0.001-0.01, P<0.05, respectively). CONCLUSION: The NLR, PLR, and SII may be used as predictors of DR.