ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

Objective:To analyze clinical characteristics of patients within 48 hours in pediatric intensive care unit（PICU）,and investigate causes and prognosis of extubation failure in reintubation children.Methods:A single-center retrospective study was conducted.Patients who were reintubated within 48 hours after extubation in PICU at Children's Hospital of Fudan University from January 1，2019 to December 31，2022 were retrospectively enrolled.Patients with unplanned extubation for various reasons which include re-intubation due to surgery and replacement of tracheal intubation were excluded.We analyzed the clinical characteristics，causes of extubation failure and prognosis.Main outcome measures included principal diagnosis，pediatric critical illness score（PCIS），the reason of intubation，the glasgow coma scale（GCS），the direct cause of reintubation，aeration time，hospitalization period，outcomes at PICU discharge and whether to extubate successfully.Results:During the study period，a total of 2 652 patients were extubated in PICU,and a total of 87 children were enrolled.Finally，63（72.4%）patients survived at PICU，nine（10.3%）patients died in hospital，and 15（17.2%）patients were discharged automatically.In the survival group，38（60.3%）patients were decannulated and 25（39.7%）patients underwent tracheotomy.The top three principal diagnosis in 87 cases were central nervous system disease[34（39.1%）cases]，lower airway disease[18（20.7%）cases] and sepsis[nine（10.3%）cases].Of the 87 children，28（32.2%）patients were reintubated due to central respiratory failure，21（24.1%）patients were reintubated due to lower airway disease，20（23.0%）patients were reintubated due to upper airway obstruction，14（16.1%）patients were reintubated due to cough weakness and/or swallowing disturbance，and four（4.6%）patients were reintubated for other reasons.In children with mechanical ventilation duration ≥7 days before first extubation，central nervous system diseases were the most common primary diseases，and it accounts for 55.6%.Central respiratory failure was the main direct cause of reintubation，accounting for 40.0%，and more patients(40.0%) had GCS scores＜8 before the first intubation.Compared with the successful decannulation group，the extubation failure group had the higher proportion of children with GCS＜8（32.7% vs.10.5%， P＜0.05），the longer median duration of mechanical ventilation before the first extubation[239（123，349）h vs.68.5（19，206）h， P＜0.05]and the longer median length of ICU stay[38（23，54）d vs.24（12，43）d， P＜0.05].After comparing the three groups including survival group，in-hospital death group and automatic discharge group，the PCIS score of the survival group was the highest，and the in-hospital death group was the lowest( P＜0.05). Conclusion:The rate of reintubation at 48 h after extubation in PICU is 3.3%.The immediate causes of reintubation mainly included central respiratory failure，lower airway disease，upper airway obstruction，cough weakness and/or dysphagia.The mortality rate of reintubation in critically ill children is high and the prognosis is poor.

Objective:To analyze the clinical situation of critically ill children with Montgomery T-tube，aiming to summarize the characteristics of T-tube application in pediatric and the experience of postoperative airway management in PICU.Methods:The etiology，clinical characteristics，complications and ICU admissions of patients with Montgomery T-tube admitted to the Pediatric Hospital of Fudan University from April 2019 to December 2021 were analyzed，and the application of T-tube in patients with critical conditions requiring long-term mechanical ventilation was described in the light of clinical experience.Results:During the study period,seven children were admitted to the PICU after T-tube insertion,including three males and four females,aged 9~75 months.Five children received mechanical ventilation.Among them,there were five cases with congenital laryngeal malformations,one case with tracheoesophageal fistula,and one case with laryngeal papilloma.The main complications were sputum blockage,infection,and granulation proliferation.One child died of secretion blockage,while the other children were successfully evacuated from the T-tube.The longest retention time of the T-tube was 367 days.Five patients experienced hoarseness after removing the T-tube,and upon re-examination with fiberoptic bronchoscopy,no recurrence of subglottic stenosis was observed.There was no respiratory distress or wheezing,and there were no abnormalities observed during regular outpatient follow-up after discharge.After discharge,the quality of life of the six surviving children improved compared to preoperative,and they all resumed oral feeding.There were no complaints of swallowing difficulties or aspiration during outpatient follow-up.But they were all combined with malnutrition.Conclusion:The Montgomery T-tube is a secure and dependable airway stent utilized for airway remodeling and the maintenance of airway patency following interventional surgery.For critically ill children,early management of airway clearance and infection prevention are imperative.

Objective To investigate the expression of fibroblast growth factor (FGF)19 in neonatal hyperbilirubinemia and its correlation with intestinal flora characteristics and β-glucuronidase (β-GD) activity. Methods Seventy-five neonates with hyperbilirubinemia in Daqing Longnan Hospital from January 2022 to January 2023 were selected as the observation group and 45 neonates with non-hyperbilirubinemia during the same period were selected as the control group.Serum FGF19,total bilirubin and total bile acid levels,intesti-nal flora characteristics and β-GD activity were compared between the two groups.The correlation between FGF19,intestinal flora and β-GD activity with serum total bilirubin level and total bile acid (TBA) level in newborns with hyperbilirubinemia and the correlation between FGF19 with the intestinal flora characteristics and β-GD activity were analyzed by the Pearson method.Results The serum FGF19 level in the observation group was lower than that in the control group,the total bilirubin and TBA levels and β-GD activity were higher,the number of bifidobacterium and Lactobacillus were much less,the number of Escherichia coli was more,and the differences were statistically significant (P<0.05).The FGF19 level and number of bifidobac-terium and Lactobacillus in newborns with hyperbilirubinemia were negatively correlated with the levels of se-rum total bilirubin and TBA levels,while the number of Escherichia coli and β-GD activity were positively cor-related with the levels of serum total bilirubin and TBA (P<0.05).FGF19 in hyperbilirubinemia neonates was positively correlated with the number of bifidobacterium and Lactobacillus,and negatively correlated with Escherichia coli and β-GD activity (P<0.05).Conclusion The serum FGF19 in neonates with hyperbilirubinemia is abnormally low expressed,moreover which is related to intestinal flora disturbance and β-GD activity.

Objective:To construct a diabetes foot prediction model for adult patients with type 2 diabetes based on retrospective cohort study using data from a regional health data platform.Methods:Using Yinzhou Health Information Platform of Ningbo, adult patients with newly diagnosed type 2 diabetes from January 1, 2015 to December 31, 2022 were included in this study and divided randomly the train and test sets according to the ratio of 7∶3. LASSO regression model and bidirectional stepwise regression model were used to identify risk factors, and model comparisons were conducted with net reclassification index, integrated discrimination improvement and concordance index. Univariate and multivariate Cox proportional hazard regression models were constructed, and a nomogram plot was drawn. Area under the curve (AUC) was calculated as a discriminant evaluation indicator for model validation test its calibration ability, and calibration curves were drawn to test its calibration ability.Results:No significant difference existed between LASSO regression model and bidirectional stepwise regression model, but the better bidirectional stepwise regression model was selected as the final model. The risk factors included age of onset, gender, hemoglobin A1c, estimated glomerular filtration rate, taking angiotensin receptor blocker and smoking history. AUC values (95% CI) of risk outcome prediction at year 5 and 7 were 0.700 (0.650-0.749) and 0.715(0.668-0.762) for the train set and 0.738 (0.667-0.801) and 0.723 (0.663-0.783) for the test set, respectively. The calibration curves were close to the ideal curve, and the model discrimination and calibration powers were both good. Conclusions:This study established a convenient prediction model for diabetic foot and classified the risk levels. The model has strong interpretability, good discrimination power, and satisfactory calibration and can be used to predict the incidence of diabetes foot in adult patients with type 2 diabetes to provide a basis for self-assessment and clinical prediction of diabetic foot disease risk.

Objective:To develop a prediction model for the risk of diabetic retinopathy (DR) in patients with newly diagnosed type 2 diabetes mellitus (T2DM).Methods:Patients with new diagnosis of T2DM recorded in Yinzhou Regional Health Information Platform between January 1, 2015 and December 31, 2022 were included in the study. The predictor variables were selected by using Lasso-Cox proportional hazards regression model. Cox proportional hazards regression models were used to establish the prediction model for the risk of DR. Bootstrap method (500 resamples) was used for internal validation, and the performance of the model was assessed by C-index, the receiver operating characteristic curve and area under the curve (AUC), and calibration curve.Results:The predictor variables included in the final model were age of T2DM onset, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, estimated glomerular filtration rate, and history of lipid-lowering agent and angiotensin converting enzyme inhibitor uses. The C-index of the final model was 0.622, and the mean corrected C-index was 0.623 (95% CI: 0.607-0.634). The AUC values for predicting the risk of DR after 3, 5, and 7 years were 0.631, 0.620, and 0.624, respectively, with a high degree of overlap of the calibration curves with the ideal curves. Conclusion:In this study, a simple and practical risk prediction model for DR risk prediction was developed, which could be used as a reference for individualized DR screening and intervention in newly diagnosed T2DM patients.

Objective:To construct a risk prediction model for diabetes kidney disease (DKD).Methods:Patients newly diagnosed with type 2 diabetes mellitus (T2DM) between January 1, 2015, and December 31, 2022, were selected as study subjects from the Yinzhou Regional Health Information Platform in Ningbo City. The Lasso method was used to screen the risk factors, and the DKD risk prediction model was established using Cox proportional hazard regression models. Bootstrap 500 resampling was applied for internal validation.Results:The study included 49 706 subjects, with an median ( Q1, Q3) age of 60.00 (50.00, 68.00) years old, and 55% were male. A total of 4 405 subjects eventually developed DKD. Age at first diagnosis of T2DM, BMI, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, past medical history (hyperuricemia, rheumatic diseases), triglycerides, and estimated glomerular filtration rate were included in the final model. The final model's C-index was 0.653, with an average of 0.654 after Bootstrap correction. The final model's area under the receiver operating characteristic curve for predicting 4-year, 5-year, and 6-year was 0.657, 0.659, and 0.664, respectively. The calibration curve was closely aligned with the ideal curve. Conclusions:This study constructed a DKD risk prediction model for newly diagnosed T2DM patients based on real-world data that is simple, easy to use, and highly practical. It provides a reliable basis for screening high-risk groups for DKD.

Objective:To explore the predictive value of methyltetrahydrofolate reductase (MTHFR) gene polymorphism in collaboration with serum ANG2 expression on the efficacy of estrogen receptor (ER) positive breast cancer chemotherapy.Methods:Sixty-six patients with ER-positive breast cancer who underwent chemotherapy were selected from Changshu First People’s Hospital from Mar. 2017 to Mar. 2022. According to the efficacy of chemotherapy, patients were divided into effective group and ineffective group. Clinical data of two groups of patients were collected, and PCR was used to detect MTHFR gene polymorphisms in leukocyte DNA and ANG2 expression in serum of patients before chemotherapy. The general data, MTHFR gene polymorphism and ANG2 level of the two groups were compared, and the factors influencing the efficacy of chemotherapy for ER-positive breast cancer were analyzed by Logistic regression. The predictive value of MTHFR gene polymorphism and ANG2 level in ER-positive breast cancer chemotherapy was analyzed according to receiver operating characteristic (ROC) curve.Results:There were 11 complete responses (CR), 38 partial responses (PR), 10 stable disease (SD), and 7 progressive disease (PD) after chemotherapy in 66 ER-positive breast cancer patients. The proportion of lymphatic metastases, the proportion of CC in C677T MTHFR gene and the level of ANG2 in serum in the ineffective group were higher than those in the effective group ( P<0.05). Logistic analysis showed that lymph metastases, C677T MTHFR gene and ANG2 level were independent risk factors for chemotherapy efficacy of ER-positive breast cancer by Logistic regression analysis ( P<0.05). ROC analysis showed that the area under the curve (AUC) values of C677T MTHFR gene and ANG2 in predicting the efficacy of chemotherapy for ER-positive breast cancer were 0.779 and 0.726, respectively, and 95% CI were 0.660-0.872 and 0.596-0.824. The combined predicted AUC value was 0.920, and 95% CI was 0.826-0.972. Conclusions:MTHFR gene polymorphism and ANG2 level are of reference value for chemotherapy efficacy of ER positive breast cancer. C677T type MTHFR gene has higher value in predicting the efficacy of ER-positive breast cancer chemotherapy in collaboration with serum ANG2 level.

Triple-negative breast cancer (TNBC) is a type of breast cancer that is difficult to treat, has a poor prognosis, and is prone to recurrence and metastasis in the early postoperative period. The age of patients is tending younger, and the racial difference is large. It is also related to family history, and genetic susceptibility is obvious. So, elucidating the genetic risk factors of TNBC and obtaining precise therapeutic targets are urgent tasks. Obtaining reliable characteristic genes and their polymorphisms between TNBC of different subtypes is difficult. This review summarizes the susceptibility genes and the polymorphisms of TNBC susceptibility genes of different molecular subtypes, in order to develop effective TNBC prevention strategies and find effective therapeutic targets. This review provides a theoretical basis for promoting the study of TNBC from the perspective of genetics.