Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective:To explore whether the food additive sodium benzoate(NAB) induces pancreatic inflammation and β cell apoptosis through the benzoylation(Kbz) modification pathway.Methods:In vivo experiments: C57BL/6J male mice(8 weeks old, 18-20 g) were randomly divided into normal control group(double distilled water feeding) and NAB feeding group(1 g/kg NAB feeding). Blood glucose were measured. After 20 weeks, fasting serum insulin, interleukin(IL)-18, IL-1β, and benzoyl-CoA levels were detected by ELISA method. Bax, IL-18, Pan-Kbz and Pan-Kac were detected by immunohistochemistry staining. In vitro experiments: β-TC-6 cells were cultured with NAB(6 mmol/L) or benzoyl-CoA(100 μmol/L) as stimulator and acyltransferase P300 inhibitor A485(10 μmol/L) as intervention factor. 24 hours later, inflammation, apoptosis, insulin secretion and Pan-Kbz level were detected by qRT-PCR, ELISA and Western blotting.Results:In the in vivo experiments, compared to the NC group, mice in the NAB group exhibited impaired glucose tolerance, decreased fasting insulin levels, significantly increased serum benzoyl coenzyme A concentrations, relatively elevated pancreatic IL-1β, IL-18, and Bax protein expressions, increased levels of Pan-Kbz, while Pan-Kac levels were downregulated(all P<0.05); In vitro experiments, NAB dose-dependently inhibited insulin secretion, promoted the release of Pan-Kbz and inflammatory factors IL-18 and TNF- α, inhibited Bcl-2 expression and up-regulated Bax expression, A485 reversed NAB-induced Pan-Kbz modification, improved NAB-induced inflammation and apoptosis, and promoted insulin secretion(all P<0.05). Conclusion:NAB may induce pancreatic inflammation, β-cell apoptosis, and impair insulin secretion through Kbz modification pathway.

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To analyze the features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infected with other common respiratory pathogens among coronavirus disease 2019 (COVID-19) patients in Shanghai City, and to provide a reference for scientific prevention and control of COVID-19 and other respiratory infectious diseases.Methods:Descriptive epidemiological approaches were used to analyze the data of COVID-19 reported cases in Shanghai City from January 2020 to February 2021 in the information system of Chinese Disease Prevention and Control. Clinical data of the participants were collected, and their SARS-CoV-2 nucleic acid-positive respiratory specimens were collected at the time of illness onset or admission. Multiplex reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the 22 respiratory pathogens. Independent-samples t test was used for statistical analysis. Results:Of the 272 patients with COVID-19, 15(5.5%) had co-infection of SARS-CoV-2 with other respiratory pathogens, all of which were double infection. There were three cases infected with enterovirus/rhinovirus, two of each with adenovirus, human metapneumovirus and coronavirus NL63/HKU1, and one of each with coronavirus 229E, influenza A virus H1N1, parainfluenza virus 1 and respiratory syncytial virus B. Two cases infected with Mycoplasma pneumoniae. Among the 272 COVID-19 patients, 212(77.9%) had fever, 117(43.0%) had cough, 46(16.9%) had fatigue, and 35(12.9%) had sore throat. The white blood cell count of co-infection cases was higher than that of non-co-infection cases ((6.8±1.7)×10 9/L vs (5.3±1.6)×10 9/L), and the difference was statistically significant ( t=3.09, P=0.008). Conclusions:There is a certain proportion of co-infection of SARS-CoV-2 with other respiratory pathogens among the COVID-19 cases in Shanghai City, mainly viral pathogens, especially enterovirus/rhinovirus. A rational combination of drugs was recommended to improve the cure rate. Surveillance of acute respiratory infection should be further strengthened as well.

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

Objective:To investigate the protective effect of liriodendrin on acute myocardial infarction in rats and to explore the related mechanisms.Methods:From January to December 2019, 30 SPF male Wistar rats with a body weight of(200±10)g were randomly divided into a sham operation group, a control group, and a liriodendringroupwith 10 rats in each group using the numerical sampling method.The liriodendron group was intragastrically administered with a liriodendrinsolution(10 ml/kg)once a day from 5 days before myocardial infarction model construction to 3 days after surgery.The control group and the sham surgery group were intragastrically administered with 10 ml/kg normal saline.After surgery, high-sensitivity troponin T levels were measured in the three groups.Cardiac function of the rats was assessed using echocardiography on the 3rd day post-surgery.Then, the rats were sacrificed, followed by hematoxylin-eosin(HE)staining and TdT-mediated dUTP nick-end labeling(TUNEL)staining of cardiac tissues and measurement of interleukin(IL)-1β and tumor necrosis factor(TNF-α)levels.Western blot and real-time polymerase chain reaction(PCR)were used to detect the expression of apoptosis-related proteins and transcriptional activity.Results:High-sensitivity troponin T levels in the liriodendrin group[(1.74±0.63)μg/L]were lower than in the myocardial infarction group[(3.54±1.60)μg/L]at 2 hours after surgery( t=2.69, P<0.05). Echocardiography showed that, compared with the myocardial infarction group, the ejection fraction was higher in the liriodendrin group, and the left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular end-diastolic volume and left ventricular end-systolic volume were lower in the liriodendrin group( P<0.05). Histological staining showed that the myocardial tissue of the control group was severely damaged, with infiltration of a large number of in flammatory cells.The number of TUNEL-positive cells in the liriodendrin group(56.66±2.414)was statistically significantly reduced, compared with in the myocardial infarction group(76.55±1.843)( t=6.55, P<0.05). The levels of IL-1β and TNF-α in the myocardial infarction group were higher than those in the liriodendrin group( P<0.05). The expression of apoptosis-related proteins in the liriodendrin group was lower( P<0.05)and the transcriptional activity of mRNA was also lower( P<0.05)than in the myocardial infarction group. Conclusions:Liriodendrin may protect cardiomyocytes after myocardial infarction in rats by inhibiting local inflammation and cell apoptosis.

Background: Fatty acid-binding protein 4 (FABP4) has been demonstrated to be a predictor of early diabetic nephropathy. However, little is known about the relationship between FABP4 and diabetic retinopathy (DR). This study explored the value of FABP4 as a biomarker of DR in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 238 subjects were enrolled, including 20 healthy controls and 218 T2DM patients. Serum FABP4 levels were measured using a sandwich enzyme-linked immunosorbent assay. The grade of DR was determined using fundus fluorescence angiography. Based on the international classification of DR, all T2DM patients were classified into the following three subgroups: non-DR group, non-proliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Multivariate logistic regression analyses were employed to assess the correlation between FABP4 levels and DR severity. Results: FABP4 correlated positively with DR severity (r=0.225, P=0.001). Receiver operating characteristic curve analysis was used to assess the diagnostic potential of FABP4 in identifying DR, with an area under the curve of 0.624 (37% sensitivity, 83.6% specificity) and an optimum cut-off value of 76.4 μg/L. Multivariate logistic regression model including FABP4 as a categorized binary variable using the cut-off value of 76.4 μg/L showed that the concentration of FABP4 above the cut-off value increased the risk of NPDR (odds ratio [OR], 3.231; 95% confidence interval [CI], 1.574 to 6.632; P=0.001) and PDR (OR, 3.689; 95% CI, 1.306 to 10.424; P=0.014). Conclusion FABP4 may be used as a serum biomarker for the diagnosis of DR.

Objective:To understand the incidence of post-traumatic stress disorder(PTSD) in fathers with premature infants and analyze the risk factors.Methods:Conveniently, the 203 fathers of premature infants in NICU of Affiliated Hospital of Jining Medical University of Shandong Province from May to August 2021 were selected as the subjects to fill in the general data questionnaire, Perinatal Post-traumatic stress disorder Questionnaire-Chinese edition (PPQ-C), Parents, Perception of Uncertainty Scale, Social Support Rating Scale, Simplified Coping Style Questionnaire. Logistic regression was used to analyze the risk factors of PTSD and establish a nomogram model. ROC curve was used to verify the discrimination ofthe model. Hosmer-Lemeshow goodness-of-fit test and Calibration Plot were used to verify the calibration.Results:PPQ-C total score of 203 fathers was 17.17 ± 8.77, 81 fathers, symptoms were positive and the incidence of PTSD was 39.90%(81/203). Logistic regression analysis showed college degree ( OR = 0.297, 95% CI 0.116 - 0.763, P<0.05), very low birth weight ( OR = 2.491, 95% CI 1.027 - 6.044, P<0.05), sense of disease uncertainty ( OR = 1.038, 95% CI 1.012 - 1.066, P<0.05), negative coping style ( OR = 1.871, 95% CI 1.127 - 3.108, P<0.05) were risk factors of PTSD in fathers with premature infants. The nomogram model was established basing on the results of the Logistic regression analysis, and the ROC curve proved (AUC = 0.751) the model having a good discrimination.The Hosmer-Lemeshow goodness-of-fit test ( P = 0.974) and the calibration plot demonstrated that the prediction values tends to coincide with the actual monitoring values. Conclusions:A higher incidence of PTSD was observed in fathers with hospitalized premature infant. It was related to education level, the infants′s birth weight, disease uncertainty and coping style. Therefore, the nurses should give information support and psychological guidance according to the individual situation of the infants′ father to reduce the incidence of PTSD.

Objective: To examine the status of self-harm, depression and anxiety and to analyze the relation of self-harm with depression and anxiety in college students. Methods: Totally 9 638 college students were randomly selected from five universities in Anhui province using stratified cluster sampling and were surveyed with basic demographic characteristics, Depression Self Rating Scale (SDS), Self-evaluation of Anxiety Scale (SAS) and self-harm behavior questionnaire. Results: The detection rate of self-harm among college students was 22.94%(2 211), boys (24.51%) were higher than girls(21.72%), the difference was statistically significant(χ2=10.46, P<0.05). The detection rate of depression was 28.57%(2 754). The detection rate of anxiety was 11.11%(1 071). The detection rate of self-harm in the depression group was 33.48%, which was significantly higher than those without depression group(18.72%)(χ2=242.22, P<0.01). The similar results were found in the anxiety analysis, students with anxiety showed higher detection rate in self-harm (48.74%) than those without anxiety (19.72%)(χ2=453.66, P<0.01). Both depression and anxiety were positively associated with self-harm behaviors(r=0.24, 0.27, P<0.01). Multivariate Logistic regression model found that after covariates controlled, depression(OR=1.48) and anxiety (OR=2.84) were positively associated with self-harm of college students(P<0.05). Conclusion Self-harm, depression and anxiety among college students in Anhui Province are at a high level, and a positive correlation between self-harm behaviors and depression and anxiety is observed. Attention should be paid to the mental health education of college students.