Individuals with type 1 diabetes or advanced type 2 diabetes suffer insufficient insulin secretion, leading to symptoms of hyperglycemia. To maintain the normal blood glucose levels, those people with diabetes must administer insulin multiple times a day. However, insulin requirements are influenced by several factors such as diet, exercise, and illness, combined with the narrow therapeutic index, making accurate insulin dosage challenging. Excessive insulin administration can even pose life-threatening risks. In addition, frequent daily insulin injections place considerable physiological and psychological burdens on patients. To tackle these challenges, researchers have embarked on the development of closed-loop insulin delivery systems. These systems adjust insulin dosages in real-time changes based on the patient’s blood glucose levels, therefore enhancing both the safety and effectiveness of insulin therapy. This review categorizes closed-loop insulin delivery systems into two types: electronic-based and material-based systems, based on their compositional attributes. The exploration of both types covers their components, developmental history, clinical applications, current pros and cons, and future directions. The relative strengths and limitations of these two categories of closed-loop insulin delivery systems are also compared and discussed.

Objective To investigate T cell subtypes and their functions in liver immune microenvironments among patients with alveolar echinococcosis (AE) using single-cell RNA sequencing (scRNA-seq). Methods Four AE patients that were admitted to Qinghai Provincial People’s Hospital in 2023 for hepatic surgery for the first time were enrolled, and liver specimens were sampled 1 cm (peri-lesion, PL group) and > 5 cm from AE lesions (distal lesion, DL group) among each patient. Finally, a total of eight liver specimens were sampled from four AE patients for scRNA-seq analysis. Genome and transcriptome data of liver specimens were processed using the software Cell Ranger and R package. Differentially expressed genes (DEGs) and their biological functions were analyzed using gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the primary intercellular communication patterns and interaction mechanisms were identified among T cell subtypes in liver specimens using the CellChat package. In addition, the developmental stages of T cells were subjected to trajectory analysis with the monocle package to investigate the expression of genes associated with cell growth and tumor transformation, and to predict the developmental trajectories of T cells. Results All four AE patients were female, with a mean age of (25.00 ± 9.06) years, and there were three cases from Jiuzhi County, Golog Tibetan Autonomous Prefecture and one case from Chengduo County, Yushu Tibetan Autonomous Prefecture, Qinghai Province. The viability of single-cell samples from eight liver specimens was 90.41% to 96.33%, and a total of 81 763 cells were analyzed, with 19 cell types annotated. Of these cell types, 13 were immune cells (87.60%), and T cells (33.13%), neutrophils (15.40%), and natural killer cells (11.92%) were the three most common cell types. Re-clustering of 27 752 T cells and proliferative T cells identified 10 distinct T cell subtypes, with CD8⁺ cytotoxic T cells (23.43%), CD8⁺ naive T cells (12.80%), and CD4⁺ effector memory T cells (17.73%) as dominant cell types. The proportions of T helper 2 (Th2) cells (5.19% vs. 3.63%; χ² = 38.35, P < 0.01) and CD4⁺ effector memory T cells (21.59% vs. 13.67%; χ² = 244.70, P < 0.01) were significantly higher in liver specimens in the PL group than in the DL group, and the proportion of CD4⁺ helper T cells was significantly lower in the PL group than in the DL group (7.50% vs. 14.75%; χ² = 330.52, P < 0.01). KEGG pathway analysis revealed that Th2 cells were significantly enriched in cell apoptosis and multiple cancer-associated pathways, and CD4⁺ effector memory T cells were significantly enriched in the regulation of cytokines and chronic inflammation, while CD4⁺ helper T cells were significantly enriched in immune responses regulation. Trajectory analysis of T cells showed that CD4⁺ helper T cells were at an earlier developmental stage relative to Th2 cells and CD4⁺ effector memory T cells, and the expression of inhibitor of DNA binding 3 (ID3), thioredoxin interacting protein (TXNIP), Bcl2-associated athanogene 3 (BAG3) and heat shock protein family B (small) member 1 (HSPB1) genes appeared a tendency towards a decline over time. Conclusions CD4⁺ effector memory T cells and CD8⁺ cytotoxic T cells are primary interacting cells in the liver specimens of AE patients. Reduced expression of Th2 cells and CD4⁺ helper T cells contributes to an inhibitory immune microenvironment, which promotes immune evasion by Echinococcus multilocularis, and Th2 cells are significantly enriched in multiple cancer-associated pathways, which may be linked to the invasive growth of E. multilocularis.

Bladder cancer is the most common malignant tumor in the urinary system.Currently,the clinical treatment options for bladder cancer mainly include surgery,chemotherapy,radiotherapy,immunotherapy,targeted therapy,photodynamic therapy,combination therapy,etc.The conventional treatment and administration strategies for bladder cancer primarily depend on the tumor stage and the extent of metastasis.However,in the process of non-surgical treatment,drugs lack specificity and targeting.Once the dosage is improperly controlled,drugs will damage normal cells when attacking cancer cells,which will lead to poor efficacy and multiple side effects.Nanomedicine is an emerging interdisciplinary field that utilizes nanomaterials and technologies in nanomedicine to provide disruptive technologies for traditional treatments,with advantages such as targeted delivery and high efficiency with low toxicity.Many nanotechnologies have become hot topics in clinical research in the field of medicine.Functionalized nanoparticles can actively or passively target specific cells within target organs,such as bladder cancer cells,by altering their surface properties,thereby enhancing drug delivery precision,reducing damage to normal cells,and improving treatment efficacy.This article provides an overview of the progress in classical and novel treatment approaches to bladder cancer,with a particular focus on the potential applications and future development directions of nanotechnology in the treatment of bladder cancer,providing important reference for personalized therapy and clinical translation in bladder cancer.

Objective To investigate the cell composition and the transcriptional characteristics in microenvironments of hepatic tissues in mice at late stage of Echinococcus multilocularis infection at a single-cell level. Methods Peri-lesion and paired distal hepatic specimens were collected from two BALB/c mice (6 to 8 weeks old) infected with E. multilocularis for single-cell RNA sequencing. The Seurat package in the R software was employed for quality control of data, multi-sample integration and correction of batch effects, and uniform manifold approximation and projection (UMAP) algorithm was used for cell clustering. Cell types were annotated using classical marker genes. Differentially expressed genes were screened in each cell type through differential gene expression analysis, and the biological roles of cells were predicted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results A total of 43 710 cells from peri-lesion and distal hepatic tissues of E. multilocularis-infected mice were analyzed, and were classified into 11 cell types, including neutrophils, T cells, macrophages, granulocyte-monocyte progenitor cells, B cells, plasma cells, basophils, hepatic stellate cells, endothelial cells, hepatocytes, and platelets. T cells were the largest population of immune cells in the microenvironment of hepatic tissues, including five CD4⁺ T cell subsets, two CD8⁺ T cell subsets and phosphoantigen-reactive γδT cells. The proportions of CD4⁺ helper T cells and cytotoxic CD4⁺ T cells decreased and the proportion of T helper 2 (Th2) cells increased in peri-lesion tissues relative to distal hepatic tissues. In addition, the differentially expressed genes in Th2 cells were associated with negative regulation of the immune system, and the highly expressed genes in cytotoxic CD4⁺ T cells correlated with activation of the immune system. Conclusions Single-cell RNA sequencing deciphers the cell composition and distribution in microenvironments of hepatic tissues from mice infected with E. multilocularis, and the increased proportion of Th2 cells in peri-lesion hepatic tissues may be associated with formation of immunosuppressive microenvironments.

Objectives:To analyze the clinical features and prognosis of patients with medullary thyroid carcinoma combined with papillary thyroid carcinoma (combined carcinoma).Methods:The clinical data of 24 patients admitted to Tianjin Medical University Cancer Hospital from Nov 2012 to Dec 2019 were retrospectively analyzed. The treatment methods, pathological results, and prognosis of all patients were examined.Results:The results showed that combined carcinoma accounted for 10.0% (24/241) of all medullary thyroid carcinoma cases. In the combined cancer group, 45.8% (11/24) patients had lymph node metastasis, and the type of metastasis matched the largest lesion. There were no significant differences in gendex ratio ( χ2=0.164, P>0.05), age at onset ( t=1.381, P>0.05), maximum diameter of lesion ( Z=-1.733, P>0.05), multifocality ( χ2=2.695, P>0.05), and lymph node metastasis in the central ( χ2=1.625, P>0.05) and lateral neck regions ( χ2=1.537, P>0.05) between combined cancer patients and those with MTC alone. The median follow-up time for the 24 patients was 77.6 months. Local recurrence was observed in 2 cases, while no distant metastasis was found. There were no significant differences in disease-free survival, disease-specific survival, and overall survival between combined cancer and pure MTC groups (all P>0.05). Conclusion:The pathological characteristics and prognosis of medullary thyroid carcinoma combined with papillary thyroid carcinoma are similar to those of pure MTC. Therefore, clinical treatment decisions can be similar to pure MTC.

Objective:This study aimed to investigate the risk features of postoperative tumor recurrence of medullary thyroid carcinoma.Methods:One hundred and seventy two patients with medullary thyroid carcinoma diagnosed at Tianjin Cancer Hospital between Jan 2010 and Jan 2018 were enrolled in this study. Based on the follow-up results, patients were divided into tumor recurrence and non-tumor recurrence group. US features,clinicopathological characteristics and somatic RET mutations were evaluated between the two groups. The cut-off values of pre-and post-operative serum calcitonin were calculated by ROC curve.Univariate and multivariate analysis were adopted between the two groups to determine independent risk factors for tumor recurrence of MTC.Tumor-free survival was determined by Kaplan-Meier analysis.Results:Univariate analysis showed that preoperative serum calcitonin≥1 367 pg/ml ( χ2=18.909, P=0.000), postoperative serum calcitonin ≥61 pg/ml ( χ2=72.278, P=0.000), mulifocality ( χ2=11.787, P=0.001),lesions in both lobes ( χ2=10.452, P=0.003), extrathyroidal invasion ( χ2=14.511, P=0.000), T3+T4-staging ( χ2=11.920, P=0.001)、TNMⅢ+Ⅳ-staging ( χ2=18.915, P=0.000), ACR TI-RADS 5 ( χ2=7.162, P=0.006) and RET mutation ( χ2=10.937, P=0.001) were significantly related to tumor recurrence of medullary thyroid carcinoma. Multivariate analysis demonstrated that postoperative serum calcitonin≥61 pg/ml ( OR=22.323, 95%CI: 6.370-78.236) and RET mutation ( OR=4.054, 95%CI: 1.354-12.139) were the independent factors related to tumor recurrence of medullary thyroid carcinoma.The survival curves of MTC patients showed a significantly lower percentage of surviving patients in the group with postoperative serum calcitonin ≥61 pg/ml ( P=0.000) or RET mutations ( P=0.001). Conclusions:Postoperative serum calcitonin ≥61 pg/ml and oncogenic RET mutation were the independent risk factors for tumor recurrence of MTC.Patients with postoperative serum calcitonin ≥61 pg/ml or a RET mutation tended to have a shorter tumor-free survival.

Objective:To explore the feasibility and clinical efficacy of oblique lateral interbody fusion (OLIF) in the treatment of adjacent segment disease (ASDis).Methods:Retrospective analysis was conducted on the data of 31 patients with ASDis treated by OLIF in four medical centers from June 2015 to December 2018. There were 17 males and 14 females. The average age was (65.7±3.4) years (range, 59 to 75 years). 19 cases received single-segment fixed fusion, 11 cases received double-segment fixed fusion and 1 case received three-segment fixed fusion. Original fixed fusion site: 1 case of L 1, 2, 3 cases of L 3, 4, 11 cases of L 4, 5, 4 cases of L 5S 1, 6 cases of L 3-L 5, 5 cases of L 4-S 1, and 1 case of L 3-S 1. The time from the initial fixation and fusion to this admission was 82.5±45.5 months (rang, 24 to 180 months). ASDis occurred at the proximal end of the fixed fusion segment in 28 cases and at the distal end in 3 cases. The types of ASDis: degenerative disc disease in 11 cases, lumbar spinal stenosis in 15 cases, degenerative spondylolisthesis in 2 cases, and degenerative scoliosis in 3 cases. The location of ASDis: 6 cases of L 2, 3, 12 cases of L 3, 4, 6 cases of L 4, 5, 3 cases of L 1-L 3, 1 case of L 2-L 4, and 3 cases of L 1-L 4. At admission, 3 cases of lumbar internal fixation had been removed and 28 cases of internal fixation remained. Stand-alone OLIF was performed in 19 cases, OLIF combined with pedicle screw fixation in 8 cases, and OLIF combined with cortical screw fixation in 4 cases. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate the low back pain and lumbar function before operation and at the last follow-up, and the imaging results and complications were observed. Results:All patients were followed up. The follow-up time was 23.6±9.6 months (range, 12 to 60 months). The operation time was 73.8±25.3 mins (range, 40 to 180 min), and the intraoperative blood loss was 86.2±67.4 ml (range, 20 to 310 ml). The average blood loss in each segment was 24.8 ml. During the operation, there were 1 case of segmental vein injury, 7 cases of endplate injury, 2 cases of transient iliopsoas muscle weakness, 1 case of thigh pain and numbness, and 1 case of incomplete intestinal obstruction. There was no incision necrosis and infection. The VAS score of low back pain decreased from 5.9±1.9 before operation to 1.4±0.6 at the last follow-up, with a statistically significant difference ( t=8.47, P<0.001). The ODI index recovered from 45.2%±5.7% before operation to 13.8%±4.7% at the last follow-up, with a statistically significant difference ( t=7.92, P<0.001). The height of intervertebral space increased from 8.7±1.6 mm before operation to 11.4±1.9 mm after operation and 9.9±1.8 mm at the last follow-up. There was a statistically significant difference between postoperative and preoperative height of intervertebral space ( F=4.15, P=0.007). There was a statistically significant difference between the last follow-up and postoperative height of intervertebral space ( P=0.011). During the follow-up, there were 13 cases of fusion cage subsidence, 1 case of fusion cage displacement, and no case of internal fixation loosening or fracture. The intervertebral fusion rate was 94%(29/31) and the complication rate was 42%(13/31). Conclusion:ASDis is a common complication after lumbar fixation and fusion, and requires surgical treatment. OLIF is a reliable method to treat ASDis as it has advantages of small trauma, high fusion rate and low complication rate.

Objective:To analyze the correlations between serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) and clinicopathological features in children and adolescents with papillary thyroid carcinoma (PTC).Methods:A retrospective analysis was conduced on the clinicopathological data of children and adolescents (age≤21 years old) with PTC admitted to Tianjin Medical University Cancer Hospital from 2011 to 2019, and then, we used χ 2 test or Fisher′s exact probability test to compare the differences in clinicopathological characteristics between groups with different TgAb and TPOAb status and multivariate logistic regression model analysis to evaluate independent predictors of cervical lymph node metastasis. Results:A total of 304 patients, including 89 males and 215 females, aged 5-21 years (median age 19 years), were enrolled in this study. The comparison between groups with different TgAb and TPOAb status showed that there were significant differences in gender, preoperative thyroglobulin (Tg) level, primary tumor location, number of primary tumors and maximum tumor diameter (all P<0.05), which suggested that TgAb +group ( n=81) and TPOAb +group ( n=84) had relatively better primary tumor characteristics. Patitents with TgAb +and TPOAb +were more common in females and their preoperative Tg level was mostly within the normal range, and there were significant differences in primary tumor location, number of primary tumors and maximum tumor diameter between TgAb +and TgAb -(223 cases) groups (all P<0.05). There was significant difference in the maximum tumor diameter between TPOAb +and TPOAb -(220 cases) groups ( P<0.05). Analysis of risk factors for cervical lymph node metastasis showed that independent risk factors for central lymph node metastasis were maximum tumor diameter>2 cm ( OR=2.84, 95% CI: 1.59-5.07, P<0.001) and extra-thyroid extension ( OR=0.32, 95% CI: 0.17-0.60, P<0.001), and independent risk factors for lateral neck lymph node metastasis included age≤14 years old ( OR=0.34, 95% CI: 0.18-0.67, P=0.002), preoperative Tg +( OR=2.16, 95% CI: 1.10-4.24, P=0.026) and maximum tumor diameter>2 cm ( OR=3.99, 95% CI: 2.33-6.82, P<0.001). Conclusion:It is recommended to test routinely serum TgAb and TPOAb before surgery in children and adolescents with PTC. Preoperative Tg +, age≤14 years, maximum tumor diameter>2 cm, and extra-thyroid extension are risk factors for cervical lymph node metastasis.

Objective:To investigate the BRAF(V600E)gene mutation of pediatric papillary thyroid carcinoma (PTC) and refine their clinicopathological correlates. Methods:Tumor tissue samples of pediatric PTCs (≤18 years old) were collected from tumor tissue bank of Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2016.The medical records of 22 patients with pediatric PTC were reviewed retrospectively.The frequencies of BRAF(V600E) mutation were evaluated and the correlation between BRAF(V600E) mutation and clinical characteristics were analyzed. Results:BRAF(V600E) mutations were present in 45.5% of cases (10 cases). BRAF(V600E) mutation in pediatric PTC was obviously lower than that in adults PTC(77.7%) ( χ2=11.250, P=0.001). BRAF(V600E) mutation in>12-year-old group (66.7%) was remarkably higher than that in ≤12-year-old group (20.0%) ( P<0.05). BRAF(V600E) mutation in female (69.2%) was greatly higher than that in male (11.1%) ( P<0.05). There was no significant correlation with BRAF(V600E) mutation and multiple tumor, tumor size, highly invasive subtype, extrathyroidal extension, lymph node metastasis and radiological history of infants (all P>0.05). The median follow-up time was 45 months.No patients died and BRAF(V600E) mutation was not associated with the increase of recurrence rate ( P>0.05). Conclusions:BRAF(V600E)gene mutation in pediatric PTC is lower than that in adults. BRAF(V600E) mutation does not portend a more aggressive clinical biological behavior in pediatric PTC.

Objective:To investigate the difference of clinicopathological characteristics between mixed medullary and papillary carcinoma of thyroid and medullary carcinoma coexistent with papillary carcinoma.Method:The clinicopathological data of 3 MMPTC cases and 9 MTC-PTC cases treated at Tianjin Medical University Cancer Institute & Hospital during the past ten years were retrospectively analyzed. The differences in clinical characteristics, pathological characteristics, immunohistochemistry results, treatment and prognosis of the two groups were compared.Results:In the MMPTC group, the median onset-age was 59 years old. 3 patients were all medullary carcinoma colliding with micropapillary carcinoma. The immunohistochemistry results showed that medullary carcinoma and papillary carcinoma showed their distinctive immunohistochemical characteristics. The lymph node metastasis rate was 66.7% (2/3). In MTC-PTC group, the median onset-age was 55; 8 out of 9 patients had an increased preoperative calcitonin level. Medullary carcinoma and papillary carcinoma showed their distinctive immunohistochemical characteristics. Four out of the 9 cases had lymph node metastasis.Conclusion:Compared with MTC-PTC, MMPTC is more common in middle-aged and elder patients, with higher lymph node metastasis rate. The pathogenesis of MTC-PTC is similar to papillary thyroid carcinoma, and the treatment should be individualized. The prognosis of these two groups of patients is fair.