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:Diabetic retinopathy (DR) has been reported as the leading cause of blindness among diabetic adults, which is closely related to poor quality of life and increased burden of disability. This study aimed to aggregate the optimally available evidence on modifiable risks of DR.Methods:Until June 2023, PubMed, Cochrane Library, CNKI, and Wanfang databases were used to retrieve Meta-analysis about various risk factors for DR, and Meta-analysis were analyzed and summarized. R 4.3.2 software was used for each Meta-analytic association to calculate the effect size, 95% CI, heterogeneity, small-study effects, excess significance bias, and 95% prediction intervals. The credibility of significant evidence was graded. Results:We captured 23 eligible papers (72 associations) covering a wide range of medication use, concomitant diseases, daily intervention, biomarkers, lifestyle, and physical measurement index. Among them, higher HbA1c variability ( RR=1.45, 95% CI: 1.26-1.66) and urine microalbumin positive ( OR=2.44, 95% CI: 1.99-2.97) were convincing (grade Ⅰ) evidence, and insulin use ( RR=3.48, 95% CI: 2.14-5.67) was highly suggestive (grade Ⅱ) evidence. Moreover, hypertension ( OR=2.03, 95% CI: 1.06-3.97), poor glycemic control ( OR=4.35, 95% CI: 1.47-12.85), positive macroalbuminuria ( OR=8.42, 95% CI: 3.52-20.15), long sleep duration ( OR=2.05, 95% CI: 1.37-3.05), vitamin D deficiency ( OR=2.02, 95% CI: 1.17-3.50), periodontitis ( OR=4.51, 95% CI: 1.76-11.55) were the main risk factors for DR. Intensive blood pressure intervention ( RR=0.78, 95% CI: 0.65-0.94), dietary control ( OR=0.64, 95% CI: 0.47-0.89) and moderate intensity physical activity ( RR=0.76, 95% CI: 0.59-0.97) yielded significant protective associations with DR. Conclusions:Intensive blood pressure glycemic control, and a healthy lifestyle pattern could reduce the risk of DR. This study provides the evidence to identify high-risk populations and recommends rational treatment options and healthy living interventions.

Objective To systematically review the efficacy of anti-inflammatory drugs in the treatment of diabetic nephropathy(DN).Methods Databases including PubMed,The Cochrane Library,EMbase,Web of Science,Scopus,Ovid,ProQuest,CBM,CNKI,WanFang Data,VIP and Duxiu data were electronically searched to collect randomized controlled trials(RCTs)of anti-inflammatory drugs for DN from inception to April 5,2022.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias of the included studies.RevMan 5.4 software were then used to perform Meta-analysis.Results A total of 29 literature and 26 RCTs involving 4 095 patients were included.The results of Meta-analysis showed that compared with conventional treatment,conventional treatment combined with anti-inflammatory drugs could effectively reduce urinary albumin to creatinine ratio[SMD=-0.17,95％CI(-0.31,-0.03),P=0.02],urinary albumin excretion rate[SMD=-0.37,95％CI(-0.56,-0.18),P=0.000 1],urinary protein excretion rate[SMD=-0.97,95％CI(-1.29,-0.64),P=0.000 01],and glycosylated hemoglobin[SMD=-0.17,95％CI(-0.27,-0.08),P=0.000 4],while there was no significant difference in reducing serum creatinine[SMD=-0.04,95％CI(-0.19,0.1),P=0.57],urea nitrogen[MD=-0.23,95％CI(-0.50,0.04),P=0.09]and fasting blood glucose[SMD=-0.15,95％CI(-0.32,0.02),P=0.08].There was no statistically significant difference in changing glomerular filtration rate(GFR)[SMD=-0.04,95％CI(-0.15,0.07),P=0.47]with multiple drugs,except for a few drugs.Conclusion Conventional treatment combined with anti-inflammatory drugs can better improve the level of proteinuria in patients with DN,but the improvement of renal function is not obvious.Due to the limitations of the number of included studies and the duration of treatment,the above conclusion needs to be verified by more high-quality studies.

Objective:To explore the clinical changes in levels of the new clinical marker serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) in patients with chronic hepatitis B (CHB) with long-term antiviral therapy.Methods:100 CHB cases who were initially treated with nucleos(t)ide analogues (NAs) at Peking University First Hospital were included. The levels of alanine aminotransferase (ALT), HBV DNA, hepatitis B e-antigen (HBeAg), and hepatitis B surface antigen (HBsAg) during the follow-up period were measured. The TaqMan-based real-time quantitative PCR method was used to detect serum HBV pgRNA levels. The independent sample t-test and Mann-Whitney U test were used to compare continuous variables between groups, while Pearson's χ2 test and Fisher's exact test were used to compare categorical variables. Results:HBV pgRNA levels decreased significantly in patients who developed virological responses at 48 weeks ( n = 54) during subsequent treatment compared to those who did not ( n = 46). The HBV pgRNA level was lower in HBeAg-positive patients than in HBeAg-negative patients ( P < 0.05 or P < 0.01). Patients with higher HBV DNA and HBeAg-positivity levels at baseline had a higher HBV pgRNA level following antiviral therapy. There was no statistically significant difference in HBV pgRNA levels in patients with different HBV pgRNA levels at baseline after antiviral therapy. There was no correlation between serum HBV pgRNA and HBsAg at baseline, but there was a correlation after long-term antiviral therapy, while there was a weak correlation between HBV pgRNA and HBsAg at the fifth and ninth years of antiviral therapy ( r = 0.262, P = 0.031; r = 0.288, P = 0.008). Conclusion:HBV pgRNA levels were higher with higher HBV activity in CHB patients with long-term antiviral therapy.

BACKGROUND: In light of the significant clinical benefits of antibody-drug conjugates in clinical trials, the human epidermal growth factor receptor 2 (HER2)-low category in breast cancers has gained increasing attention. Therefore, we studied the clinicopathological characteristics of Chinese patients with hormone receptor (HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model. METHODS: Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery (CSBrS) from Jan 2015 to Dec 2016 were enrolled. Their clinicopathological data and prognostic information were collected, and machine learning methods were used to analyze the prognostic factors. RESULTS: In total, 25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016, and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected. Among them, 5629 patients (86.79%) were HR-positive. The median follow-up time was 57 months (4, 76 months); the 5-year disease-free survival (DFS) rate was 92.7%, and the 5-year overall survival (OS) rate was 97.7%. In total, 412 cases (7.31%) of metastasis were observed, and 124 (2.20%) patients died. Multivariate Cox regression analysis revealed that T stage, N stage, lymphovascular thrombosis, Ki-67 index, and prognostic stage were associated with recurrence and metastasis ( P <0.05). A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%, specificity of 71.7%, positive predictive value of 74.1%, and negative predictive value of 79.2%. CONCLUSION: Most of patients with HER2-low early-stage breast cancer were HR-positive, and patients had favorable outcome; tumor N stage, lymphovascular thrombosis, Ki-67 index, and tumor prognostic stage were prognostic factors. The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events. REGISTRITATION ChiCTR.org.cn, ChiCTR2100046766.
Humans ; Female ; Breast Neoplasms/diagnosis* ; Ki-67 Antigen ; Receptor, ErbB-2 ; Prognosis ; Thrombosis ; Receptors, Progesterone

BACKGROUND: : Breast cancer with low-positive human epidermal growth factor receptor 2 (HER2) expression has triggered further refinement of evaluation criteria for HER2 expression. We studied the clinicopathological features of early-stage breast cancer with low-positive HER2 expression in China and analyzed prognostic factors. METHODS: : Clinical and pathological data and prognostic information of patients with early-stage breast cancer with low-positive HER2 expression treated by the member units of the Chinese Society of Breast Surgery and Chinese Society of Surgery of Chinese Medical Association, from January 2015 to December 2016 were collected. The prognostic factors of these patients were analyzed. RESULTS: : Twenty-nine hospitals provided valid cases. From 2015 to 2016, a total of 25,096 cases of early-stage breast cancer were treated, 7642 (30.5%) of which had low-positive HER2 expression and were included in the study. After ineligible cases were excluded, 6486 patients were included in the study. The median follow-up time was 57 months (4-76 months). The disease-free survival rate was 92.1% at 5 years, and the overall survival rate was 97.4% at 5 years. At the follow-up, 506 (7.8%) cases of metastasis and 167 (2.6%) deaths were noted. Multivariate Cox regression analysis showed that tumor stage, lymphvascular invasion, and the Ki67 index were related to recurrence and metastasis (P < 0.05). The recurrence risk prediction model was established using a machine learning model and showed that the area under the receiving operator characteristic curve was 0.815 (95% confidence interval: 0.750-0.880). CONCLUSIONS: : Early-stage breast cancer patients with low-positive HER2 expression account for 30.5% of all patients. Tumor stage, lymphvascular invasion, and the Ki67 index are factors affecting prognosis. The recurrence prediction model for breast cancer with low-positive HER2 expression based on a machine learning model had a good clinical reference value for predicting the recurrence risk at 5 years. TRIAL REGISTRATION : ChiCTR.org.cn, ChiCTR2100046766.
Breast Neoplasms/metabolism* ; Female ; Humans ; Ki-67 Antigen ; Mastectomy ; Receptor, ErbB-2/metabolism*

Objective     To investigate activated toll-like receptor-4 (TLR4) signaling pathway involved in pathophysiological mechanisms of type A aortic dissection (TAAD). Methods     Specimens of full-thickness ascending aorta wall from the TAAD patients (n=12) and the controlled donors (n=12) were collected. Western blotting was used to examine the associated proteins' expression of TLR4 signaling pathway. Blood samples from TAAD (n=43) and controlled patients (n=50) were examined by enzyme-linked immunosorbent assay (ELISA) to detect the circulating plasma cytokines levels of interleukin-1β (L-1β). Results     In the aortic wall of TAAD, expression levels of TLR4 and protein expression of major molecule significantly elevated, and activated macrophages increased. Furthermore, elevated IL-1β levels were observed in the TAAD patients’ plasma compared with the control plasma. Multiple logistic regression analysis and receiver operating characteristic (ROC) curve showed that elevated IL-1β could be a novel and promising biomarker with important diagnostic and predictive value in the identification of TAAD. Conclusion     Activated TLR4/NF-κB signaling pathway regulates inflammatory response to involve in pathophysiological mechanisms of type A aortic dissection and its regulated inflammatory products have important predictive value for patients with TAAD.

Objective To observe the influences on prognoses and airway acid and base levels while using anti-inflammatory and anti-reflux therapies combined with "Hezhong Fuzheng massage" for treatment of infants with gastric volvulus (GV) and gastroesophageal reflux (GER)-induced pneumonia in order to provide evidence for clinical diagnosis and treatment of such infant disease. Methods Sixty infants 1-6 months old admitted to the Department of Integrated Traditional Chinese and Western Medicine of Wuhan Children's Hospital from January 2013 to December 2015 were diagnosed as pneumonia combined with GV and GER by the chest radiograph and radiography of upper gastrointestinal tract (UGT) with iodine, and according to difference in diagnostic methods, they were divided into an observation 1 group (30 cases) and an observation 2 group (30 cases). In observation 1 group, 24-hour pH value in upper digestive tract especially the distal esophagus was dynamically monitored, while in observation 2 group, 24-hour multichannel intraluminal impedance (MII) combined with pH monitoring of esophagus was carried out. Furthermore, two control groups were set up, each 30 cases; after radiography of the UGT with iodine, the control 1 group was diagnosed as GV and GER without pneumonia and control 2 group was diagnosed as only simple GV. Treatment of infant pneumonia was carried out in accordance with the guidelines for the management of community-acquired pneumonia in children; the treatment of GV and GER included postural, dietary, prokinetic and Hezhong Fuzheng massage [acupoint selection and massage was undertaken in 5 steps: push from the palmar crease to Banmen (rectilinear pushing manipulation) 300 times, push abdominal Yin and Yang (finger-pushing massage) 200 times, palpate the abdomen (clockwise) 100 times, poking of Tianshu 100 times, poke alternately bilateral Zusanli 100 times. Once-daily massage, (15±2) minutes each time, for consecutive 7 days]. The results of pH monitoring of the distal esophagus in observation 1 group was recorded; All GER data concerning pH monitoring of observation 2 group and the results of esophagus multi-channel intra-luminal impedance combined with pH monitoring in control group were compared. After 7 days of continuous treatment, the clinical efficacy of pneumonia and GV, hospitalization time, prognosis and the changes of sputum pH before and after treatment in the two observation groups were compared. Results In two observation groups, the main type of 60 cases with GV was organoaxial volvulus, accounting for 91.67% (55 cases), and more than 60% patients exhibited sputum pH <7.0. The distal esophagus 24-hour pH dynamic monitoring in observation 1 group showed that there were 26 cases with acid reflux (86.67%), 4 cases with GER negative (13.33%), the proportion of pH < 4 in GER negative patients was significantly lower than that in moderate acid reflux patients [3.35% (0.77% - 8.08%) vs. 26.23% (15.19% - 42.87%), P < 0.05], the number of long reflux (> 5 minutes) in GER negative patients was significantly reduced than that in mild acid reflux patients [times: 2 (0-5) vs. 7 (2-15), P < 0.05], the longest time of reflux in GER negative patients was significantly shorter than that in either mild or moderate acid reflux patients [minutes: 5.9 (2.5-10.0) vs. 19.2 (5.9-51.0), 41.6 (16.9-121.0), both P < 0.05]. The 24-hour MII-pH monitoring of esophagus in observation 2 group showed that there were 30 cases with pathological reflux, mainly mild acid reflux accounting for 90%, in which the percentage of proximal reflux events was 46.07% in the total reflux events. The numbers of acid reflux and proximal reflux in the observation 2 group were significantly higher than those in the control 1 and 2 groups [1 305 (37.72%) vs. 795 (25.69%) and 136 (18.89%), 1 594 (46.07%) vs. 687 (22.20%) and 154 (21.39%), both P < 0.05]; there were no significant differences in total effective rate (100% vs. 100%, P > 0.05) and hospitalization time (days: 7.58±1.09 vs. 7.67±1.12, P > 0.05) between the two observation groups. Conclusions For the diagnosis of infant pneumonia combined with GV and GER, the first selection of chest radiograph and radiography of the UGT with iodine can identify the severity of pneumonia, whether it is complicated with GV and its classification, and whether GER exists at the same time. The estimation of 24-hour pH dynamic monitoring of the acid reflux in the upper digestive tract especially the distal esophagus is consistent with that of the 24-hour MII-PH monitoring of esophagus. Moreover, 24-hour MII-PH monitoring of esophagus can also identify non-acid reflux, resulting in the GER diagnosis more accurate. Since the proximal reflux ratio of infants with GV combined with GER and pneumonia is relatively high and easy to cause cough and aspiration. attention should be paid on early diagnosis and timely intervention to such patients. The sputum acidity test can reflect the airway acid-base level and its manipulation is simple, so by that the real time disease situation can be estimated, and aspiration of sputum also can help the treatment. The therapeutic schedule formulated by our group can elevate the therapeutic effect, improve the airway acid-base environment and benefit prognosis.