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 evaluate the effect of mesenchymal stem cell (MSC) coated-islets on instant blood-mediated inflammatory reaction (IBMIR) after islet transplantation. Methods MSC labeled with tracer and human islets were placed into an ultra-low adsorption cell culture dish, shaken and mixed twice at an interval of 0.5 h, and then incubated at 37 ℃ and 5% CO₂ for 24 h to obtain MSC-coated islets. The coating effect of MSC and in vitro function of the islets were assessed. A blood circulation tube-shaped model was established in vitro. In the blank control group, 0.2 mL of islet culture solution was added. In the islet group, 800 islet equivalent quantity (IEQ) of uncoated islets were supplemented. In the MSC-coated islets group, 800 IEQ of MSC-coated islets were added, and circulated for 60 min at 37 ℃. A portion of 0.5 mL blood sample was taken for routine blood test at 0, 30 and 60 min, respectively. After 60 min circulation, the blood sample was filtered with a 70 μm filter to collect plasma, blood clots and islets. Blood clots and islets were subject to hematoxylin-eosin (HE) staining and immunohistochemical staining. Morphological changes and the aggregation of CD11b-positive cells surrounding the islets were observed. The contents of plasma thrombin-antithrombin complex (TAT), tissue factor (TF), C3a, C5b-9, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1 and IL-8 were determined by enzyme-linked immune absorbent assay. Results After 24 h co-incubation, the islets were coated by MSC, with a coating degree of approximately 80%. In the islet and MSC-coated islet group, a large quantity of neutrophils and monocytes were observed surrounding the blood clots and islets, and the quantity of CD11b-positive cells in the MSC-coated islet group was less compared with that in the islet group. After co-incubation with the whole blood for 0, 30 and 60 min, the quantity of platelets, neutrophils and monocytes was declined in the MSC-coated and islet groups, and gradually decreased over time. Compared with the blank control group, the quantity of platelets, monocytes and neutrophils was lower, whereas the TF content was higher in the MSC-coated islet group. Compared with the islet group, the quantity of platelets, monocytes and neutrophils was higher, whereas the TAT and TF contents were less in the MSC-coated islet group, the differences were statistically significant (all P < 0.05). Compared with the blank control group, the expression levels of C3a, C5b-9, IL-6, TNF-α and IL-8 were up-regulated in the MSC-coated islet group. Compared with the islet group, the expression levels of C3a, C5b-9, IL-1β, IL-6, TNF-α, IL-8 and MCP-1 were down-regulated in the MSC-coated islet group, and the differences were statistically significant (all P < 0.05). Conclusions MSC-coated islets may reduce the exposure of islet TF in the blood and prevent the incidence of IBMIR during the coagulation response stage, thereby mitigating the injury and loss of islet allograft in the early stage of islet transplantation.

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Objective:To systematically evaluate the relationship between sedentary behavior (SB) and the risk of developing gestational diabetes mellitus (GDM).Methods:PubMed, Medline, EMBASE, CINAHL, the Cochrane Library, the Rehabilitation & Sports Medicine Source, the Sedentary Behavior Research Database (SBRD), Wanfang Database, the China Journal full-text database, and the China Biomedical Literature Database were searched for cohort studies, case-control studies, and cross-sectional studies concerning the risk of SB and GDM from the establishment of the database to January 2021. Two researchers screened the literature, extracted data, evaluated the quality of the data according to the inclusion and exclusion criteria, and, finally, produced a descriptive analysis of the results.Results:A total of 11 studies were included, including eight cohort studies, two cross-sectional studies, and one case-control study. The overall quality of the studies was moderate. The prevalence of GDM was 5.04%-26.81%, and the prevalence of SB before and during pregnancy was 39.47%-40.21% and 28.86%-93.50%, respectively. In terms of the prevalence of SB before pregnancy, four moderate-quality studies reported no association with GDM risk. In terms of SB during pregnancy, four moderate-quality studies reported no association with GDM risks, and four studies (one of high quality and three of moderate quality) reported an association with GDM risks, two of which focused on the second trimester. There was considerable heterogeneity between studies on the diagnosis of GDM and SB.Conclusion:SB before pregnancy is not associated with the risk of GDM, while the relationship between SB and the risk of GDM is unclear, but the level of SB in the second trimester of pregnancy may be positively associated with the risk of GDM.

Objective:To investigate the characteristics of serum cytokine IL-4 and IFN- γ levels in patients with chronic insomnia with mild cognitive impairment (MCI), and to further explore the relationship between cognitive function and IL-4 and IFN-γ in patients with chronic insomnia.Methods:Sixty-two patients with chronic insomnia were divided into MCI group( n=30) and non-MCI group( n=32) according to the scores of Montreal cognitive assessment(MoCA), mini-mental state examination(MMSE) score and chief complaint of cognitive decline. Pittsburgh sleep quality index(PSQI), Hamilton depression scale(HAMD 24) and Hamilton anxiety scale 14 item(HAMA 14) were evaluated. Serum IL-4 and IFN-γ were detected by flow fluorescence, correlation analysis and regression analysis were carried out. Results:The levels of IL-4 and IFN-γ in MCI group were significantly lower than those in non-MCI group (IL-4: 0.875(0.143, 1.655)μg/L, 1.855(0.813, 2.723)μg/L; IFN-γ: 0.450(0.173, 1.163)μg/L, 1.160(0.483, 3.075)μg/L, all P<0.05). There was no significant difference in IFN- γ/IL-4, PSQI, HAMA 14 and HAMD 24 scores between MCI group and non-MCI group. IL-4 was positively correlated with the total score of MoCA( r=0.318, P<0.05), orientation( r=0.324, P<0.05)and delayed recall( r=0.368, P<0.01). The results of multivariate regression showed that IL-4 had significant effects on MCI in patients with chronic insomnia( B=2.161, OR=8.682, 95% CI=2.058~36.633, P=0.003). Conclusion:The cognitive function of chronic insomnia is closely related to serum IL-4 and IFN-γ, and serum IL-4 has a protective effect on cognition in chronic insomnia patients. Therefore, it can be speculated that cytokines may be an important pathophysiological link of cognitive change in chronic insomnia patients.

This report is about the application of interventional therapy for bladder rectal residual fistula in a patient whose postoperative rectal stump tumor invaded the bladder and underwent radiotherapy and chemotherapy, resulting in urinary fistula, which seriously affected the quality of life. Referring to the treatment experience of visicovaginal fistula, the patient successfully adopted double percutaneous nephrostomy combined with ureter occlusion stent and achieved good palliative treatment effect.

Objective: To evaluate the role of prognostic nutritional index (PNI) in the radiotherapy for elderly patients with esophageal squamous cell carcinoma. Methods: Clinical data of 108 elderly patients (aged>65 years) with esophageal squamous cell carcinoma who underwent radical radiotherapy were retrospectively analyzed. The PNI value of each patient was calculated, and the optimal cutoff value of PNI before treatment was determined by establishing the receiver operating characteristic curve (ROC curve). All patients were divided into the low and high PNI value groups. The overall survival rate was calculated by Kaplan-Meier method. Log-rank test, univariate and Cox’s multivariate prognosis analyses were performed. Results: The ROC curve demonstrated that the optimal cutoff value of PNI was 50.1(n=52 in high PNI group and n=56 in low PNI group). Age, gender and treatment did not significantly differ between two groups, whereas the TNM staging significantly differed (P=0.022). The effective rate of radiotherapy in the high PNI group was 96%, significantly higher than 73% in the low PNI group (P=0.001). In the high PNI group, the 1-, 2-, and 3-year overall survival rates were 94%, 69%, and 62%, significantly higher compared with 70%, 32% and 27% in the low PNI group (all P<0.001). Univariate analysis showed that PNI, T staging, N staging and TNM staging were significantly correlated the overall survival of patients (all P<0.01). Cox’s multivariate analysis revealed that N staging (RR=1.94, 95%CI=1.29-2.94, P=0.002) and PNI (RR=0.83, 95%CI=0.77-0.90, P<0.001) were independent risk factors affecting overall survival. Conclusions PNI before treatment has a good correlation with the prognosis and radiotherapy efficacy of patients, which can be used as a pivotal index to predict the clinical benefit of radiotherapy for elderly patients with esophageal squamous cell carcinoma.

Objective To investigate the protective effect and mechanism of serum containing Euonymus fortunei on the rat pancreatic islet cells. Methods Forty male SD rats were randomly divided into 5 groups (n=8 in each group), including the control group (normal rat islet cells were cultured with normal rat serum), ischemic preconditioning group (abdominal aorta was blocked first and then re-opened before the pancreas was obtained, and the pancreatic islet cells were cultured with normal rat serum), Euonymus fortunei treatment group (normal rat islet cells were cultured with rat serum containing Euonymus fortunei), Euonymus fortunei group and blank group (normal rats were administered orally with Euonymus fortunei extract or distilled water for the preparation of rat serum). Diphenylthiocarbazone (DTZ) staining was utilized to observe and calculate the quantity of islets. Acridine orange (AO)/propidium iodide (PI) staining was adopted to calculate the survival rate of islet cells. The insulin release experiment was performed to calculate the stimulation index (SI) and evaluate islet cell function. The concentration of glutathione (GSH) and nitric oxide (NO) in islet cells was detected using GSH and NO kits. The expression level of inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) was quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). Results Islet cells were observed in specifically scarlet color after DTZ staining. The quantity of islet cells did not significantly differ among different groups (all P>0.05). Along with the prolongation of culture time, the activity of islet cells in each group was gradually decreased. At 72 h after isolation and culture, compared with the control group, the survival rate of the cells was significantly higher in the Euonymus fortunei treatment group (P<0.05). The insulin release test results demonstrated that compared with the control group, the SI of the ischemic preconditioning and Euonymus fortunei treatment groups was significantly increased (both P<0.05). Compared with the control group, the GSH contents of pancreatic islet cells in the ischemic preconditioning and Euonymus fortunei treatment groups were considerably enhanced, the NO content was significantly decreased, and the expression level of iNOS mRNA was significantly down-regulated (all P<0.05). Conclusions Euonymus fortunei can increase the survival rate of islet cells and enhance the function of pancreatic islets by increasing the level of GSH, down-regulating the expression of iNOS and decreasing the NO production.

Objective To evaluate the effects of the size of lymph node metastasis (LNM) on the chemoradiotherapy efficacy and prognosis for the patients after resection of thoracic esophageal squamous cell carcinoma (ESCC).Methods Between 2011 and 2014,a total of 75 esophageal squamous carcinoma patients with secondary LNM after resection of ESCC were recruited in this retrospective study.They were treated with curative radiotherapy only or concurrent chemoradiotherapy in the Affiliated Taixing People's Hospital of Yangzhou University.Thc LNM volume and maximum diameters were measured by the Monaco treatment planning system.The enrolled patients were grouped according to the median values of LNM volume and maximum diameters.The relationship between the responsiveness to treatment and these markers was analyzed by univariate and multivariate logistic analysis.The Kaplan-Meier method and Log-rank test were adopted to calculate and compare the overall survival (OS) rates with these markers.The Cox proportional hazards model was used to carry out univariate and multivariate analyses.Results The overall effective rate was 69.3％ for all enrolled patients.The response rates were 81.6％ with LNM volume ＜57 cm3 and 56.8％ with LNM volume ≥57 cm3.The response rates were 83.8％ with LNM maximum diameter ＜ 5 cm and 55.3％ with LNM maximum diameter ≥5 cm.The responses to treatment were highly associated with treatment method (OR =1.825,95％ CI:1.134-3.658,P =0.017),LNM volume (OR =4.183,95％ CI:1.416-12.354,P =0.010) and maximum diameter (OR =3.374,95％ CI:1.185-9.611,P =0.023) by univariate logistic regression analysis.Multivariate logistic regression analysis showed that therapeutic method (OR =1.225,95％ CI:1.085-2.837,P =0.038) and LNM volume (OR =1.614,95％ CI:1.003-3.025,P =0.048) were independent risk factors for tumor response.The median OS time of this cohort was 14 months,and the 1,2 and 3 year OS rates were 60.7％,25.3％ and 20.1％,respectively.Kaplan-Meier survival analysis revealed that TNM stage (HR =2.039,95 ％ CI:1.234-3.370,P =0.005),treatment methods (HR =1.858,95 ％ CI:1.385-2.958,P =0.013),LNM volume (HR =2.642,95％ CI:1.552-4.497,P ＜ 0.001) and LNM maximum diameter (HR =3.399,95 ％ CI:1.939-5.958,P ＜ 0.001) were significantly associated with OS.Furthermore,multivariate Cox proportional hazard regression model analysis for OS was performed and the results showed that TNM stage (HR =2.023,95 ％ CI:1.149-3.560,P =0.015),LNM volume (HR =2.055,95 ％ CI:1.041-4.055,P =0.038) and maximum diameter (HR =1.910,95％ CI:1.137-3.895,P =0.045) were considered as independent prognostic risk factors for OS.Conclusion LNM volume in ESCC patients with secondary LNM after esophagectomy has great values for predictive therapeutic effects and survival outcomes,and LNM maximum diameter has significant value for survival outcomes.

Objective To discuss the pathological and clinical characteristics,treatments and prognosis of schwannoma of the kidney.Methods Two cases of schwannoma of the kidney in our hospital were reviewed with clinicopathological data and their follow-up.The related literatures were reviewed.The first case was a male patient,28 years old,complained about paroxysmal abdominal pain with nausea over 2 weeks.The physical exam found a 10 cm,qualitative hard,poor activity,tenderness mass in kidney region.MRI preoperative diagnosis was right renal cell carcinoma with renal vein and inferior vena cava tumor thrombus formation.The second patient,female,53 years old,the mass on upper right kidney was found occasionally.It was diagnosed as adrenal pheochromocytoma before operation,laparoscopic resection of right renal hilum mass and right partial adrenectomy plus right nephrectomy were performed.There was no tumor recurrence in the follow-up.Results The abdominal aortography and double renal arteriography were done and right renal artery embolization and inferior vena cava filter were allocated.Then right radical nephrectomy and inferior vena cava tumor thrombus removal were carried out on the first patient.The first malignant and the second benign renal schwannoma patient showed significant difference in pathological presentations.Their immunohistochemistry also showed great diversity.Malignant renal schwannoma was significantly stained by Ki-67 ＞ 40％,S-100 was negative.Ki-67 in benign neurilemmomas was about 2％,and S-100 in benign renal schwannoma was positive.Conclusions Schwannoma of the kidney is rare with a favorable prognosis.The golden standard of diagnosis is pathology.Surgical resection has become the first choice for treatment.Recurrence and malignant transformation would happen after the surgery so that all the patients should be followed up.