Objective To explore the therapeutic mechanism of compound Yuye Decoction against diabetic cardiomyopathy(DCM).Methods Drugbank,Gene Cards,OMIM and PharmGKb databases were used to obtain DCM-related targets,and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis.The"Traditional Chinese Medicine-Key Component-Key Target-Key Pathway"network was constructed using Cytoscape 3.9.1,and molecular docking was carried out for the key components and the core targets.In the animal experiment,Wistar rat models of DCM were treated with normal saline or Yuye Decoction by gavage at low(0.29 g/kg)and high(1.15 g/kg)doses for 8 weeks,and the changes in cardiac electrophysiology and histopathology were evaluated.The changes in serum levels of LDH,CK,and CK-MB were examined,and myocardial expressions of PI3K,P-PI3K,Akt,P-AKT,BAX,IL-6,and TNF-α were detected using Western blotting.Results We identified 61 active compounds in Yuye Decoction with 1057 targets,3682 DCM-related disease targets,and 551 common targets between them.Enrichment of the core targets suggested that apoptosis,inflammation and the PI3K/Akt pathways were the key signaling pathways for DCM treatment.Molecular docking studies showed that the active components in Yuye Decoction including gold amidohydroxyethyl ester and kaempferol had strong binding activities with AKT1 and PIK3R1.In DCM rat models,treatment with Yuye Decoction significantly alleviated myocardial pathologies,reduced serum levels of LDH,CK and CK-MB,lowered myocardial expressions of BAX,IL-6 and TNF-α,and increased the expressions of P-PI3K and P-AKT.Conclusion The therapeutic effect of compound Yuye Decoction against DCM is mediated by its multiple active components that act on multiple targets and pathways to inhibit cardiomyocyte apoptosis and inflammatory response by regulating the PI3K/Akt signaling pathway.

Objective To explore the therapeutic mechanism of compound Yuye Decoction against diabetic cardiomyopathy(DCM).Methods Drugbank,Gene Cards,OMIM and PharmGKb databases were used to obtain DCM-related targets,and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis.The"Traditional Chinese Medicine-Key Component-Key Target-Key Pathway"network was constructed using Cytoscape 3.9.1,and molecular docking was carried out for the key components and the core targets.In the animal experiment,Wistar rat models of DCM were treated with normal saline or Yuye Decoction by gavage at low(0.29 g/kg)and high(1.15 g/kg)doses for 8 weeks,and the changes in cardiac electrophysiology and histopathology were evaluated.The changes in serum levels of LDH,CK,and CK-MB were examined,and myocardial expressions of PI3K,P-PI3K,Akt,P-AKT,BAX,IL-6,and TNF-α were detected using Western blotting.Results We identified 61 active compounds in Yuye Decoction with 1057 targets,3682 DCM-related disease targets,and 551 common targets between them.Enrichment of the core targets suggested that apoptosis,inflammation and the PI3K/Akt pathways were the key signaling pathways for DCM treatment.Molecular docking studies showed that the active components in Yuye Decoction including gold amidohydroxyethyl ester and kaempferol had strong binding activities with AKT1 and PIK3R1.In DCM rat models,treatment with Yuye Decoction significantly alleviated myocardial pathologies,reduced serum levels of LDH,CK and CK-MB,lowered myocardial expressions of BAX,IL-6 and TNF-α,and increased the expressions of P-PI3K and P-AKT.Conclusion The therapeutic effect of compound Yuye Decoction against DCM is mediated by its multiple active components that act on multiple targets and pathways to inhibit cardiomyocyte apoptosis and inflammatory response by regulating the PI3K/Akt signaling pathway.

Hypertension heightens the risk of cardiovascular and renal complications in individuals with type 2 diabetes mellitus. Optimal blood pressure (BP) management is crucial for preventing these complications. This review consolidates evidence from clinical trials and major BP management guidelines to shed light on key aspects of hypertension management in diabetes. It addresses BP thresholds to initiate antihypertensive treatment, optimal BP control targets, recommended first-line antihypertensive edications, and BP monitoring plan for the prevention of chronic complications in type 2 diabetes.

Objective:To analyze the disease spectrum of lysosomal storage disorders(LSDs) and explore the prevalent distributions of different LSD types in one center in Shanghai.Methods:A retrospective analysis was made.A total of 5 476 suspected LSD patients, including 3 415 males and 2 061 females, with a median age of 4 years(1 day to 72 years), were collected from Xinhua Hospital, Shanghai Jiaotong University School of Medicine from August 2008 to May 2022.The activity of different lysosomal enzymes was detected by fluorescent and biochemical methods.Results:A total of 1 520 patients were diagnosed with LSDs, including 972 males and 548 females, with a median age of 4 years(1 day to 59 years), involving 19 different subtypes.Mucopolysaccharidosis(MPS) was the most common type among LSDs, with a frequency of 45.46%(691/1 520), followed by sphingolipidoses [33.88%(515/1 520)] and glycogen storage disease type Ⅱ [16.05%(244/1 520)] successively.MPS Ⅱ was the most common type in MPS, with a frequency of 45.73%(316/691), followed by MPS ⅣA [22.87%(158/691)]. Niemann-Pick A/B, Gaucher, and Krabbe diseases were common in Sphingolipidoses patients, with frequencies of 37.09%(191/515), 34.37%(177/515), and 10.29%(53/515), respectively.Conclusions:LSDs are common genetic metabolic diseases, especially MPS and sphingolipidoses.Newborn screening for LSDs should be carried out timely so that the patients can be treated early and their prognosis can be improved.

Objective:To explore the predictive value of 18F-FDG PET/CT metabolic parameters combined with inflammatory markers for the medium-term efficacy of chemotherapy in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL). Methods:From April 2011 to May 2020, 67 patients (37 males, 30 females, age: 28-85 years) with PGI-DLBCL examined by 18F-FDG PET/CT before chemotherapy in Changhai Hospital, Navy Medical University were retrospectively analyzed. All patients were treated with cyclophosphamide+ doxorubicin+ vincristine+ prednisone (CHOP) or rituximab+ CHOP (R-CHOP) regimens, and the medium-term efficacy was evaluated after 2-4 cycles of chemotherapy. The effect outcome was divided into complete remission (CR) group and non-CR (NCR) group based on the Lugano lymphoma response evaluation criteria. Mann-Whitney U test was used to compare the differences of SUV max, peak of SUV (SUV peak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) between two groups. The independent risk factors of NCR were analyzed by multivariate logistic regression and the binary logistic regression model was established according to the results. The model was tested with external validation data ( n=15). Results:Of 67 PGI-DLBCL patients, 28(41.8%) were CR and 39(58.2%) were NCR. SUV peak, MTV, TLG, PLR and NLR in NCR group (17.3(12.3, 28.1), 73.8(42.9, 141.7) cm 3, 887.5(300.9, 2 075.3) g, 203.9(155.7, 297.1), 3.9(3.0, 4.9)) were significantly higher than those in CR group (9.5(6.2, 15.2), 11.3(4.7, 23.2) cm 3, 85.2(35.5, 214.6) g, 149.3(102.8, 173.1), 2.2(1.8, 4.6); z values: from -6.41 to -2.33, all P<0.05). The logistic regression model was as follows: P=1/(1+ e - x), x=0.100×MTV+ 0.024×PLR-8.064. The prediction accuracy for NCR risk was 86.57%(58/67), with the accuracy of 13/15 tested by external validation data. Conclusion:MTV combined with PLR has a good predictive value for medium-term efficacy of CHOP/R-CHOP chemotherapy in patients with PGI-DLBCL.

Objective:To explore the expression of the nucleotide-binding oligomerization domain-like receptor containing pyrin domain protein 6 (NLR family,pyrin domain containing 6,NLRP6) in the gastric tissue and gastric juice of children with chronic non-atrophic gastritis (CNG), and to analyze the influence of Helicobacter pylori (Hp) infection on the expression of NLRP6.Methods:A case-control study was conducted to select 120 CNG patients in pediatrics of Department of Pediatrics, The Affiliated Hospital of Xuzhou Medical University from October 2020 to July 2021. According to pathological diagnosis, endoscopic gastric mucosal damage and Hp infection, they were divided into 4 groups: mild CNG group Hp negative, Moderate to severe CNG group Hp negative, Mild CNG group Hp positive, Moderate to severe CNG group Hp positive. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression level of NLRP6 in the four groups of gastric tissue and gastric juice, and Western blot was used to detect the expression of NLRP6 in the gastric tissue of the 4 groups, and the significance of expression in CNG of children is analyzed. Independent sample t-test was used to compare the mean between the two groups. One way ANOVA was used to compare the mean of multiple groups of samples, and LSD t-test was used for pairwise comparison. Comparison between count data groups χ 2 inspection. Results:The positive rate of Hp in the moderate to severe chronic non-atrophic gastritis group was 62.96% (34/54) higher than that in the mild chronic non-atrophic gastritis group 37.04% (20/54), and the difference was statistically significant (χ 2=18.32, P<0.001). Under the same Hp conditions, the expression of NLRP6 in the mild chronic non-atrophic gastritis group (Hp negative mild CNG: gastric tissue (653.73±37.71) ng/L, gastric juice (471.75±38.47) ng/L; Hp positive mild CNG: Gastric tissue (616.69±43.33) ng/L, gastric juice (445.29±36.39) ng/L was higher than the moderate to severe chronic non-atrophic gastritis group (Hp negative moderate to severe CNG: gastric tissue (623.82±52.99) ng/L, gastric juice (446.48±47.49) ng/L; Hp positive Moderate to severe CNG: gastric tissue (580.43±62.75) ng/L, gastric juice (406.88±51.85) ng/L, the difference is statistically significant (under Hp negative, mild compared with moderate to severe CNG: gastric tissue P=0.035; gastric juice P=0.046; Under Hp positive, mild compared with moderate to severe CNG: gastric tissue P=0.010;gastric juice P=0.002); in the same degree of gastric mucosal injury, NLRP6 expression in Hp-negative group (Hp-negative mild CNG: gastric tissue (653.73±37.71) ng/L, gastric juice (471.75±38.47) ng/L; Hp negative moderate to severe CNG: gastric tissue (623.82±52.99) ng/L, gastric juice (446.48±47.49) ng/L higher than the positive group (Hp positive mild CNG: gastric tissue (616.69±43.33) ng/L, gastric juice (445.29±36.39) ng/L; Hp positive moderate to severe CNG: gastric tissue (580.43±62.75) ng/L, gastric juice (406.88±51.85) ng/L, the difference is statistically significant (under mild CNG, Hp negative is compared with positive: Gastric tissue P=0.005; gastric juice P=0.023; under moderate to severe CNG, negative versus positive: gastric tissue P=0.004; gastric juice P=0.003). Conclusion:Under the same Hp conditions, the more severe the gastric mucosal damage, the lower the NLRP6; under the same degree of mucosal damage, the expression level of NLRP6 in the Hp-negative group was significantly higher than that of the Hp-positive group. It is suggested that NLRP6 plays a role in inhibiting inflammation in chronic gastritis, maintaining the integrity of epithelial cells, and Hp can inhibit the expression of NLRP6.

Objective:Nuclear magnetic resonance spectroscopy (NMR) was used to detect the species and content of metabolites in urine of patients with inherited metabolic diseases, and to explore the application value of NMR technology in the diagnosis of inherited metabolic diseases.Methods:Urine samples were collected from 20 patients with inherited metabolic diseases diagnosed in Xinhua Hospital, Shanghai Jiaotong University School of Medicine from March to June 2019, including 9 cases of methylmalonic acidemia (MMA). NMR pulse length-based concentration determination and Gas chromatography mass spectrometry (GC/MS) semi-quantitative method were used to detect the composition of metabolites in urine samples of patients with inherited metabolic diseases, and the levels of abnormal metabolites in the two methods were analyzed.Results:NMR technology can detect the levels of characteristic metabolites significantly increased in the urine of patients with MMA, isovalerinemia, glutaric acidemia, propionic acidemia, 3-methylcrotonyl-CoA carboxylase deficiency, ornithine carbamyltransferase deficiency, Citrin deficiency, Canavan disease, tyrosinemia and lysinuria protein intolerance. The average is 8 times of the upper limit of the reference value, and the highest is 545 times. Compared to GC/MS, NMR technology can detect the levels of various metabolites such as organic acids, amino acids and sugars. In 9 cases of untreated MMA,the median levels of methylmalonic acid and 3-hydroxypropionic acid in NMR [1 800 (180-12 000) and 50 (0-270) mmol/mol Cr] were higher than the reference values (0-31, 0-35). The median levels of methylmalonic acid and methylmalonic acid in GC/MS [136.56 (43.79-518.67) and 4.87 (1.52-7.52)] were higher than the reference values (0-4 and 0-0.7).Conclusions:NMR and GC/MS technologies are specific for the diagnosis of organic acidemia. The primary component detected by GC/MS is organic acid. NMR technology can break through this limitation and measure the level of various metabolites in urine, which provides a more theoretical basis for the diagnosis and research of inherited metabolic disease.

Objective:To summarize the echocardiography and pathological features of fetal Kabuki syndrome.Methods:This study retrospectively analyzed the echocardiography and pathological features of seven fetuses with KMT2D pathogenic variants confirmed by copy number variation sequencing, and who were identified as complex congenital heart disease by fetal echocardiography, at Beijing Anzhen Hospital, Capital Medical University and other multi-center collaborative hospitals on fetal congenital heart diseases from January 2013 to May 2018. All the seven fetuses were artificially aborted. Descriptive statistics were used for data analysis. Results:(1) The seven pregnant women aged 29 (27-32) years and had an abortion at 23 (22-25) gestational weeks. There were three male and four female fetuses. (2) Pathogenic mutations in KMT2D gene were detected in all seven cases, including one nonsense mutation and six frameshift mutations. (3) All fetuses had left heart obstruction with or without aortic arch dysplasia/interruption of the aortic arch. There were three with hypoplastic left heart syndrome, two with a single ventricle, one with aortic atresia, and one with severe mitral valve dysplasia. Other cardiovascular abnormalities included aortic arch branch abnormalities, double-outlet of the right ventricle, ventricular septal defect, tricuspid atresia, pulmonary valve stenosis (nearly atresia) complicated by pulmonary dysplasia, persistent left superior vena cava, and patent or closed foramen ovale. Secondary changes included enlargement of the right atrium and right ventricle, and dilatation of the pulmonary artery or ductus arteriosus. (4) Four of the seven fetuses showed multiple extracardiac system abnormalities, including facial deformities (two cases), pulmonary dysplasia (two cases), digestive abnormalities(two cases), and urogenital system abnormalities (two cases). Conclusions:The main features of echocardiography for fetal Kabuki syndrome are left heart obstruction, often complicated by other congenital cardiovascular abnormalities.

Objective: The aim of the present study was to investigate the survival rate and its prognostic factors for patients with biliary tract cancer, and then a prognostic risk prediction model was constructed to predict the survival probability of patients. Methods: A total of 14 005 patients with biliary tract cancer (including gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer), who were diagnosed between 2010 and 2015 in the US National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER) were included in the development cohort. The prognostic risk factors of biliary tract cancer were investigated using multivariate Cox regression models. The predictive nomograms were then constructed to predict the overall survival probability of 1, 3, and 5 years, and the predictive discrimination and calibration ability of the nomograms were further evaluated. Meanwhile, 11 953 patients who were diagnosed during 2004 to 2009 from SEER Program were then selected to validate the external predictive accuracy of the prediction models. Results: The 1, 3 and 5-year cumulative survival rates of patients with biliary tract cancer were 41.9%, 20.4% and 15.3%, respectively, in the development cohort. Age greater than 50 years, African Americans and Native Americans and Alaska Natives, higher T, N and M stage and poor histological differentiation grade were risk factors for death, while married status, Asia-Pacific Islanders, insured status and surgery on primary site were protective factors. Gender was not significantly associated with the overall survival. The C statistic of the prediction model was 0.73 (95%CI: 0.72-0.74), and the calibration curve showed that the interaction curves of predictive and actual survival rates of 1, 3 and 5 years were close to the 45 degree diagonal. Results in the validation cohort were similar with those in the construction cohort, with a C statistic of 0.70 (95%CI: 0.69-0.72), indicating high external applicability of the prediction model. Findings from gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer are in consistent with the overall biliary tract cancer. Conclusions The survival rate of patients with biliary tract cancer is relatively poor, and the survival prediction model based on prognostic factors has high prediction accuracy. In the future, this prognostic prediction model could be applied to clinical practice to guide individualized treatment for patients with biliary tract cancer.

Objective: To analyze the echocardiographic features and prognosis of fetal pulmonary artery sling (PAS). Methods: In this retrospective study, clinical information of 13 PAS cases diagnosed by fetal echocardiography in Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2016 to December 2018 were collected. Echocardiographic characteristics and complications of intracardiac and extracardiac malformations were summarized. Their outcomes were also analyzed. Results: (1) Two out of the 13 pregnant women continued their pregnancies until delivery, while the other 11 terminated the pregnancies. One neonate received surgery in another hospital after birth and was followed up to one year old with normal growth and development. The other infant was lost to follow up after birth. (2) Among the 13 cases, 12 were complete PAS and one (case 13) was partial PAS. Nine cases were complicated by other intracardiac malformations and five by extracardiac malformations. (3) Pulmonary artery development: Echocardiographic data of ten cases (the other three cases were excluded due to absence of detailed echocardiographic information) revealed that one fetus had tetralogy of Fallot with the diameter of pulmonary valve under normal value, while the pulmonary valve diameters of the other nine cases were all within the normal range. The inner diameter of the left and the right pulmonary artery that below the normal values were observed in four and two cases, respectively. One case showed absent distal end of right pulmonary artery with right pulmonary dysplasia, but the normal inner diameter at the beginning of right pulmonary artery. Conclusions Fetal PAS is more likely to be complicated by persistent left superior vena cava (PLSVC) and ventricular septal defect (VSD) as well as left and right pulmonary artery stenosis. The prognosis of PAS may be improved if operation is performed after birth, but further studies are needed.