Objectives To analyze the role and mechanisms of mast cells in the inflammation and fibrosis of 2 ,4, 6-trinitrobenzene sulfonic acid (TNBS)-induced rat pancreatic fibrosis. Methods Rats were received the aseptic instillation of TNBS in ethanol via bilo-pancreatic duct, and then injected with nedocromil sodium, a mast cell stabilizer, and compound 18/80, a mast cell activator, or saline. Rats were sacrificed respectively on 3, 7, 14, 21 or 28 days. Pancreatic inflammation and fibrosis were assessed by gross and histopathological evaluation. Pancreatic fibrosis were observed by Van Gieson. Pancreatic mast cells distribution, number and their state of activation (toluidine blue) were evaluated. The activation of pancreatic stellate cells (PSCs) were assessed by the expression of a-smooth muscle actin (?-SMA) through immunohistochemistry. The expression of angiotensin Ⅱ AT1 and AT2 receptors and transforming growth factor (TGF) ? 1 raRNA, which were the factors of fibrogenesis, were also assessed. Results Typical pancreatic fibrosis changes occurred in the model of rats received TNBS at 4th week by morphological evaluation. The positive expression of ?-SMA and TGF?1 in the pancreatic tissues were detected at day 3, especially at 4th week. The expression of angiotensin Ⅱ AT1 and AT2 receptors mRNA increased gradually in all the three groups, also especially at 4th week. Compared to the control group, there were more higher expression of ?-SMA, TGF?1, angiotensin Ⅱ AT1 and AT2 receptor in the compound 48/80 group, while there were lower expression of these proteins in the nedocromil group. Conclusions Mast cells are involved in TNBS-induced pancreatic inflammation and fibrosis in rats. After being activated, mast cells will promote the activation and proliferation of PSCs and upregulate the expression of angiotensin Ⅱ AT1 receptor and AT2 receptor, and then lead to pancreatic fibrosis gradually.

Objective:To explore auxiliary therapeutic effect of exercise intervention on hypertension and/or diabetes mellitus (DM) .Methods :A total of 456 patients with hypertension and/or DM from community were selected and randomly equally divided into intervention group (n=228 ,wore exercise amount monitor ,and lifestyle disease inte‐grated control software was used to monitor exercise ,and unique person provided quantitative exercise guidance for them for three months and they were followed up for eight times ) and control group (n=228 ,did routine activity as usual) .Body weight ,BMI ,waist circumference (WC) ,blood pressure ,blood sugar ,blood lipid etc .and exercise a‐mount were measured and compared between two groups before and after intervention .Results:Compared with be‐fore intervention ,there were no significant changes in all above indexes in control group after intervention , P>0.05 all;there were significant reductions in body weight ,BMI ,WC ,blood pressure ,blood sugar ,blood lipid etc . in intervention group after intervention ( P< 0.01 all) .After intervention ,compared with control group , there were significant reductions in body weight [ (68.28 ± 8.43) kg vs . (65.93 ± 10.43) kg] ,blood pressure [ (124.32 ± 13.70 /77.81 ± 8.22) mmHg vs . (120.94 ± 8.35 /74.58 ± 5.76) mmHg] ,HbA1c [ (7.12 ± 1.53) mmol/L vs . (6.73 ± 1.04) mmol/L] ,LDL‐C [ (2.72 ± 0.40) mmol/L vs . (2.46 ± 0.67) mmol/L] ,and significant rose in total exercise amount [ (537.85 ± 338.63) kcal vs .(637.15 ± 447.65) kcal] ,effective exercise amount [ (229.46 ± 239.04) kcal vs . (323.56 ± 257.84) kcal] in intervention group ,P<0.01 all .Conclusion:Exercise can improve ex‐ercise capacity ,reduce blood pressure ,blood sugar ,blood lipid levels ,is help to disease control and quality of life improvement in patients with hypertension and/or diabetes mellitus .

OBJECTIVETo investigate the characteristics of the phenylalanine hydroxylase (PAH) gene mutations in patients with phenylketonuria (PKU) in Tianjin and surrounding area, in order to provide basic information for genetic counseling and prenatal gene diagnosis.

METHODSAll of the 13 exons and flanking introns of the PAH gene from 99 patients with PKU were amplified by polymerase chain reaction and analyzed by single strand conformation polymorphism (SSCP), denaturing high performance liquid chromatography (DHPLC) and DNA sequencing.

RESULTSMutations were found in all exons or flanking introns of the PAH gene except for exons 9 and 13. A total of 41 different mutations were identified which corresponded to 93.94% (186/198) of the PAH alleles, including 22 missense mutations (53.6%), 7 nonsense mutations (17.1%), 9 splicing junction mutations(22.0%), and 3 deletion mutations (7.3%). Six novel mutations (IVS3nt+1g--> a, A165D, Q301X, G344D, P362L and R413G) were identified and another 6 mutations (S16fsdelCT, R71H, IVS5nt+1g--> a, G239S, R243X and R261X) were reported in Chinese population for the first time according to the databases from http://www.pahdb.mcgill.ca. The most common mutations included 243Q (36/198,18.18%), V399V (22/198, 11.1%), R111X (19/198, 9.6%), E6nt-96A--> g (18/198, 9.1%), R413P (15/198, 7.6%) and Y356X (13/198, 6.6%). In addition, 4 silent mutations (except V399V) in exons and 8 variations in introns were found in this study. The IVS1nt+40t--> g and IVS10nt-31g--> a were confirmed as novel variations by international PAH databases and IVS5nt-54g--> a was the first report in China.

CONCLUSIONThe frequencies of six common mutations were close to that in Beijing area of China, but it was different in sequence. The extensive mutation spectrum of the PAH gene showed higher heterogeneity in Tianjin and surrounding areas of Northern China comparing with other reports. According to this report, exons 7 and 11 are the hot spots and should be detected first for PAH gene quick diagnosis in this area, then comes exons 3, 6 and 12, and finally exons 5, 10 and others.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Child, Preschool ; China ; Exons ; Female ; Humans ; Infant ; Infant, Newborn ; Introns ; Male ; Molecular Sequence Data ; Mutation ; Phenylalanine Hydroxylase ; genetics ; Phenylketonurias ; enzymology ; genetics ; Sequence Analysis, DNA

Objective:To observe and compare the clinical characteristics between post-chronic pancreatitis diabetes mellitus(PPDM-C)patients and type 2 diabetes mellitus(T2DM).Methods:Data of 142 cases of CP patients confirmed in Shanghai Pudong New Area Gongli Hospital from January 2018 to December 2021 were collected, all the patients were divided into CP group without diabetes mellitus ( n=60) and PPDM-C group with diabetes mellitus ( n=82) based on whether with or without diabetes mellitus. And 82 cases T2DM without CP (T2DM group, n=82) hospitalized simultaneously were collected as control group. The age, sex, body mass index, onset characteristics, laboratory examination indicators at admission (fasting blood glucose, glycosylated hemoglobin, blood creatinine, and alanine transaminase), imaging characteristics of the pancreas (pancreatic atrophy, multiple calcifications of the pancreas, pancreatic duct stones, pancreatic duct dilation, and pancreatic duct obstruction), and treatments and efficacy of diabetes were recorded. Results:Compared with T2DM group, PPDM-C group had lower body mass index (22.2 kg/m 2vs 24.6 kg/m 2), and glycosylated hemoglobin levels (7.34% vs 9.20%) (all P values <0.001), higher alanine transaminase levels (33.00 U/L vs 18.65 U/L, P =0.021). And they had more upper abdominal pain, nausea, vomiting, weight loss and diarrhea symptoms. In addition, they had less use of combination of insulin and hypoglycemic drugs to control blood glucose. And compared with CP group, PPDM-C group had higher body mass index (22.06 kg/m 2vs 21.18 kg/m 2), higher glycosylated hemoglobin levels (7.34% vs 5.70%), higher fasting blood-glucose levels (7.91 mmol/l vs 5.31 mmol/l), higher alanine transaminase levels (33.00 U/L vs 26.50U/L), and their differences were statistically significant (all P values <0.05). And they had higher incidence of pancreatic atrophy, multiple calcifications in the pancreatic duct and pancreatic duct obstruction (all P values <0.05). Conclusions:PPDM-C patients are more likely to experience digestive system symptoms such as abdominal pain than T2DM patients, while their pancreatic malfunction is more likely to occur compared to CP patients. More attentions to PPDM-C associated clinical manifestations, biochemical and imaging changes could identify patients at potential risk for early diagnosis and treatment earlier.

Objective To study the outcomes of Lennox-Gastaut syndrome (LGS) with single-stage total corpus callosotomy combined with different resective surgeries. Methods Nine LGS patients, admitted to our hospital from May 2010 to May 2014, were chosen in our study. Their clinical data were retrospectively analyzed. According to the results of anatomy, electrophysiology and clinical comprehensive evaluation, all the 9 children received single-stage total corpus callosotomy combined with different resective operations. The differences of epileptic seizures of these children before and after surgery were compared. Results The 9 LGS children were followed up for 2 years;5 achieved Engel grade I, 3 achieved Engel grade II, and one achieved Engel grade III. The surgical effective rate was 88.9％ (8/9). The frequencies of drop seizures, convulsive seizures, tonic seizures and tonic-clonic seizures were decreased of different degrees, with drop seizures enjoying the best control. Three patients had transient silence, remarkable relief one week after surgery and total recovery half year after surgery. Conclusion Early single-stage total corpus callosotomy combined with different resective operations can help to control seizures in children with intractable LGS.

The structure of N-glycans on specific proteins can regulate innate and adaptive immunity via sensing environmental signals. Meanwhile, the structural diversity of N-glycans poses analytical challenges that limit the exploration of specific glycosylation functions. In this work, we used THP-1-derived macrophages as examples to show the vast potential of a N-glycan structural interpretation tool StrucGP in N-glycoproteomic analysis. The intact glycopeptides of macrophages were enriched and analyzed using mass spectrometry (MS)-based glycoproteomic approaches, followed by the large-scale mapping of site-specific glycan structures via StrucGP. Results revealed that bisected GlcNAc, core fucosylated, and sialylated glycans (e.g., HexNAc₄Hex₅Fuc₁Neu5Ac₁, N₄H₅F₁S₁) were increased in M1 and M2 macrophages, especially in the latter. The findings indicated that these structures may be closely related to macrophage polarization. In addition, a high level of glycosylated PD-L1 was observed in M1 macrophages, and the LacNAc moiety was detected at Asn-192 and Asn-200 of PD-L1, and Asn-200 contained Lewis epitopes. The precision structural interpretation of site-specific glycans and subsequent intervention of target glycoproteins and related glycosyltransferases are of great value for the development of new diagnostic and therapeutic approaches for different diseases.
Humans ; B7-H1 Antigen ; Glycosylation ; Polysaccharides/metabolism*