In recent years， hyperuricemia （HUA） has shown a rapidly increasing incidence and tends to occur in increasingly young people， with a wide range of cardiac， renal， joint， and cancerous hazards and all-cause mortality associations. Western medicine treatment has limitations such as large liver and kidney damage， medication restriction， and easy recurrence. The intestine is the major extra-renal excretion pathway for uric acid （UA）， and the intestinal microecology can be regulated to promote UA degradation. It offers great potential to develop UA-lowering strategies that target the intestinal microecology， which are promising to provide safer and more effective therapeutic approaches. Traditional Chinese medicine （TCM） can treat HUA via multiple targets and multiple pathways from a holistic view， with low toxicity and side effects. Studies have shown that intestinal microecology is a crucial target for TCM in the treatment of HUA. However， its specific mechanism of action has not been fully elucidated. Focusing on the key role of intestinal microecology in HUA， this review explores the relationship between intestinal microecology and HUA in terms of intestinal flora， intestinal metabolites， intestinal UA transporters， and intestinal barriers. Furthermore， we summarize the research progress in TCM treatment of HUA by targeting the intestinal microecology， with the aim of providing references for the development of TCM intervention strategies for HUA and the direction of future research.

Metabolic diseases have seen a steady increase in incidence in recent years, becoming one of the main causes of sub-health status globally. Neutrophil extracellular traps(NETs) are reticular complexes containing DNA, which trap foreign microorganisms or induce an immune response. Current research indicates that NETs are widely active in various metabolic diseases and can cause severe damage to the body through multiple mechanisms, including promoting blood glucose elevation, damaging vascular endothelial cells, forming vascular embolisms, triggering intense inflammation, and promoting lipid accumulation. Therefore, intervening in NETs is an important approach to treating metabolic diseases. Research has shown a close relationship between the theory of spleen heat-turbid toxin theory and metabolic diseases-NETs mechanism. The basic pathogenesis include the internal accumulation of phlegm-dampness, qi stagnation and blood stasis, internal accumulation of dampness-heat, phlegm and blood stasis, and flourishing toxic heat. Various Chinese herbal medicines with the functions of dispelling dampness, resolving phlegm, promoting blood circulation to remove blood stasis, and clearing heat and toxins, along with their extracts and compound prescriptions, can treat metabolic diseases by regulating NETs and delaying disease progression. This paper systematically outlined the formation mechanisms of NETs, their connection to metabolic diseases, the theoretical basis in TCM, their roles in numerous metabolic diseases, and the current research status of TCM in regulating NETs to prevent and control metabolic diseases, aiming to provide effective reference ideas for developing therapeutic strategies for metabolic diseases.
Humans ; Extracellular Traps/metabolism* ; Metabolic Diseases/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Neutrophils/metabolism* ; Medicine, Chinese Traditional

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

The global outbreak of monkeypox in 2022 has aroused widespread concern in public health. To date, the prevention and treatment of monkeypox has mainly relied on smallpox vaccines and drugs. This study aims to screen and obtain therapeutic antibodies with high affinity, neutralizing activity, and protective effects, and provide candidate molecules for the development of specific therapeutic antibodies against monkeypox. Therefore, humanized mice were immunized to screen for antibodies against the envelope protein of the mpox virus. Two M1R-specific antibodies, 12G5 and 12H6, were obtained, with the affinity of 0.095 nmol/L and 0.089 nmol/L, respectively. The 50% reduction of the plaque counts (PRNT₅₀) of 12G5 and 12H6 was (1.821±1.766) μg/mL and (17.605±2.383) μg/mL, respectively. The two antibodies targeted two binding epitopes of M1R. Moreover, 12H6 could protect 60% of mice from death following the vaccinia virus challenge. This study provides research materials for subsequent in-depth studies on the immunoprotection of mpox virus and potential therapeutic strategies.
Animals ; Mice ; Antibodies, Viral/immunology* ; Monkeypox virus/immunology* ; Mpox, Monkeypox/immunology* ; Antibodies, Neutralizing/immunology* ; Viral Envelope Proteins/immunology* ; Humans ; Antibodies, Monoclonal/biosynthesis* ; Female

Flow cytometry (FCM) is an interdisciplinary cell analysis technology that integrates optics, fluid dynamics, electronics, and computer science. While FCM is widely utilized in diagnosing and monitoring hematologic malignancies, its application in nonhematopoietic neoplasms (NHN) remains in its nascent stages. However, recent advancements in science and technology have led to the emergence of innovative FCM technologies, such as mass spectrometry flow cytometry (CyTOF) and spectral flow cytometry (SFC), offering promising avenues for their clinical application aiming to assist the clinical diagnosis of NHN patients. This review summarizes the features of fundamentals of traditional FCM, CyTOF, and SFC technologies, along with their applications and future prospective in NHN diagnosis and treatment, aiming to offer updated insights for the continued expansion and utilization of FCM technology in clinical laboratory settings.

Objective:To develop the real-time radiotherapy monitoring system of three-dimensional (3D) point cloud by using depth camera and verify its feasibility.Methods:Taking the depth camera coordinate system as the world coordinate system, the conversion relationship between the simulation CT coordinate system and the world coordinate system was obtained from the calibration module. The patient's simulation CT point cloud was transformed into the world coordinate system through the above relationship, and registered with the patient's surface point cloud obtained in real-time manner by the depth camera to calculate the six-dimensional (6D) error, and complete the positioning verification and fractional internal position error monitoring in radiotherapy. Mean and standard deviation of 6D calculation error, Hausdorff distance of point cloud after registration and the running time of each part of the program were calculated to verify the feasibility of the system. Fifteen real patients were selected to calculate the 6D error between the system and cone beam CT (CBCT).Results:In the phantom experiment, the errors of the system in the x, y and z axes were (1.292±0.880)mm, (1.963±1.115)mm, (1.496±1.045)mm, respectively, and the errors in the rotation, pitch and roll directions were 0.201°±0.181°, 0.286°±0.326°, 0.181°±0.192°, respectively. For real patients, the translational error of the system was within 2.6 mm, the rotational error was approximately 1°, and the program run at 1-2 frames/s. The precision and speed met the radiotherapy requirement. Conclusion:The 3D point cloud radiotherapy real-time monitoring system based on depth camera can automatically complete the positioning verification before radiotherapy, real-time monitoring of body position during radiotherapy, and provide error visual feedback, which has potential clinical application value.

Objective:To investigate the clinical features of diagnosis and treatment of renal parenchymal invasive urothelial carcinoma.Methods:The clinical data of 23 patients with renal parenchymal invasive urothelial carcinoma admitted to Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2014 to December 2020 were retrospectively analyzed. There were 12 males and 11 females. The mean age was (67.3±10.1) years old. Among them, 7 cases complained of painless hematuria and 9 cases were asymptomatic. Three cases underwent preoperative MRI examination, 19 patients underwent preoperative enhanced CT examination, and 1 patient underwent both MRI and enhanced CT examination. MRI examination showed renal lobulated and other T1 mixed with T2 signals, the boundary was not clear, and DWI showed obvious restricted diffusion. The tumor was located on the left side in 15 cases and on the right side in 8 cases. Preoperative diagnosis was made by fine needle aspiration biopsy in 1 patient, and specimens were obtained by flexible ureteroscope in 2 patients. No tumor was reported. The preoperative diagnosis of 22 patients was unclear and the nature of the tumor could not be determined. One patient was considered to have urothelial carcinoma by fine needle aspiration. All patients were treated by surgery, including 20 cases of laparoscopic radical nephrectomy and 3 cases of nephroureterectomy with bladder sleeve resection.Results:Postoperative pathological specimens showed yellow-white mass, high-grade invasive urothelial carcinoma invading renal parenchyma. Nine cases were T 3a stage, 14 cases were T 3b stage, and 5 cases were lymph node metastasis. The average postoperative follow-up time was (18.6±6.72)months, 2 patients were lost to follow-up, 8 patients died, and the overall mortality rate was 38.1%. Seven patients died of recurrence or metastasis. There were 3 cases of bladder recurrence and 5 cases of metastasis after operation. Conclusions:Renal parenchymal infiltrating urothelial carcinoma is difficult to diagnose in the early stage, with poor clinical biological behavior and poor overall prognosis. For patients diagnosed with renal parenchymal invasive urothelial carcinoma preoperatively, laparoscopic nephroureterectomy + bladder sleeve resection is recommended.

Diabetic cardiomyopathy （DCM） is one of the complications of diabetes. It refers to a specific type of idiopathic cardiomyopathy that occurs in individuals with diabetes， distinct from other cardiovascular diseases such as coronary heart disease， valvular heart disease， or congenital heart disease. It has also been identified as one of the leading causes of death in diabetic patients for many years. Research has shown that the pathogenesis of DCM is closely associated with insulin resistance， activation of various inflammatory responses， increased oxidative stress， impaired coronary microcirculation， and accumulation of advanced glycation end products （AGEs）. Among various inflammatory responses， the activation of the NOD-like receptor protein 3 （NLRP3） inflammasome can induce the secretion of a large amount of pro-inflammatory cytokines through the cascade reaction of inflammation， subsequently mediating cellular pyroptosis and promoting myocardial damage. Currently， extensive experimental studies on traditional Chinese medicine （TCM） have been conducted in China and abroad based on the significant role of the NLRP3 inflammasome in the prevention and treatment of DCM. These studies have demonstrated that Chinese medicinal extracts， such as Astragalus polysaccharide and ginsenoside Rb₁， single drugs like Coriolus and Cordyceps， and Chinese medicinal formulas like Didangtang and modified Taohe Chengqitang， as well as acupuncture and TCM exercise therapy， can regulate the relevant pathways of the NLRP3 inflammasome to inhibit its assembly or activation， reduce inflammatory responses， inhibit myocardial remodeling in DCM， and improve cardiac function. This article reviewed the relationship between the NLRP3 inflammasome and DCM， as well as the research progress on TCM in exerting anti-inflammatory effects in this field， aiming to provide new insights for the development of therapeutic approaches for DCM.

Objective:To construct a cycle dual-task network based on cycleGAN to implement 3D CT synthesis from single-view projection for adaptive radiotherapy of thoracic tumor and then evaluate image quality and dose accuracy.Methods:A total of 45 thoracic tumor patients admitted to the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University were collected, and 991 cases were also selected from public dataset as pretrained dataset. Multi-view projections were acquired by ASTRA algorithm. The public dataset was divided into a training set of 800 cases, a validation set of 160 cases and a test set of 31 cases. The dataset obtained from patients in our hospital was divided into a training set of 40 cases and a test set of 5 cases. The network included synthetic CT model and multi-view projection prediction model and achieved the dual-task training. The final test only used the synthetic CT model to acquire the predicted CT images and deliver image quality [mean absolute error (MAE), peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM)] and dose evaluation.Results:Image quality evaluation metrics for synthetic CT showed high image synthesis accuracy with MAE of 0.05±0.01, PSNR of 19.08±1.69, SSIM of 0.75±0.04, respectively. The dose distribution calculated on synthetic CT was also close to the actual dose distribution. The mean 3%/3 mm γ pass rate for synthetic CT was 93.1%.Conclusions:A dual-task cycle network modified on cycleGAN has been implemented to rapidly and accurately predict 3D CT from single-view projection, which can be applied to the workflow of adaptive radiotherapy for thoracic cancer. Both image generation quality and dosimetric evaluation demonstrate that synthetic CT can meet the clinical requirements for radiotherapy.

Objective To investigate the dosimetric effect of truncated regions in computed tomography (CT) images on the targets and organs at risk in volumetric modulated arc therapy (VMAT) for middle thoracic esophageal cancer. Methods CT images of 15 patients with middle thoracic esophageal cancer were selected. Circle masks were used to make the volume of the truncated region account for 10%, 20%, 30%, and 40% of the arm volume, and the corresponding truncated CT images were obtained. The real CT was denoted as CT0. Two radiotherapy plans were made on CT0. One plan was VMAT_1F with full arcs, and the other one was VMAT_3F with arm avoidance. The plans were transplanted to four truncated CT, respectively, and the dosimetric differences between different plans were compared using Wilcoxon signed-rank test. Results Compared with VMAT_1F in CT0, D_mean and V₅ of the lung decreased in VMAT_3F, but D_max of the spinal cord, D_mean of the heart, and V₂₀ of the lung increased. In VMAT_3F, there was no statistically significant difference between the dosimetric parameters in the four truncated CT and those in CT0 (all P > 0.05). In VMAT_1F, except for homogeneity index and D_max of the spinal cord, the dosimetric parameters in four truncated CT were significantly different from those in CT0 (P < 0.05). The dosimetric difference increased with the increase in truncated region-to-volume ratio. Conclusion Complete CT data should be collected in clinical practice, and the radiation field avoiding the truncated regionshould be set if necessary to reduce the influence of the truncated region on dosimetry.