Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

Objective To identify the key biomarkers for diagnosing chronic obstructive pulmonary disease(COPD)complicated with pulmonary arterial hypertension(PAH)using bioinformatics,and validate their clinical significance.Methods High-throughput sequencing data analysis was employed to identify differentially expressed genes(DEGs)in COPD-PAH.Functional enrichment analysis was then conducted to explore the biological functions of these DEGs.Machine learning methods,including least absolute shrinkage and selection operator(LASSO),random forest(RF),and support vector machine-recursive feature elimination(SVM-RFE),were utilized to screen 5 potential biomarkers.Single-cell analysis was performed to reveal the expression patterns of these key genes in macrophages.The clinical significance of these biomarkers was further validated using peripheral blood mononuclear cells(PBMC)data.A mouse model of COPD-PAH was established using hypoxia exposure.Sixteen mice(either sexes,8 weeks old,weighing 20～22 g)were randomly divided into a hypoxia group[O2(10.0±0.5)%,COPD-PAH,n=8]and a normoxia group(COPD,n=8).Immunofluorescence assay was used to label the key biomarkers,and their expression levels were quantified.Results A total of 28 DEGs(|Log2FC|≥2,P<0.05)were identified in COPD-PAH patients.Functional enrichment analysis indicated that DEGs in COPD were primarily associated with major histocompatibility complex(MHC)Ⅱ and cell division,and involved in lysosomes,oxidative phosphorylation,and cell cycle pathways(P<0.05).Machine learning identified 5 potential biomarkers(GRN,KLF4,SHTN1,LRP1,and GPNMB),and subsequent single-cell analysis revealed that these markers exhibited reverse expression patterns during disease progression.A nomogram model constructed based on PBMC data yielded an area under the curve(AUC)of 0.907 in diagnosing COPD-PAH.GRN,KLF4,SHTN1,LRP1 and GPNMB were significantly upregulated in the COPD-PAH group(P<0.05).Conclusion GRN,KLF4,SHTN1,LRP1 and GPNMB are identified as key biomarkers for the prediction and diagnosis of COPD-PAH,which providing new insights for the clinical and treatment of the condition.

Objective To scan and accurately reconstruct mandible models printed via fused deposition modeling(FDM)that contain screw path information,using cone-beam CT(CBCT),to achieve the digital transfer of preoperative model screw paths.Methods CBCT scans were conducted on 12 FDM-printed mandibular models(Model1 group)intended for prebending reconstruction plates.Mim-ics software was employed to reconstruct scanned data into mandibular models(Model2 group)and extract digital screw path informa-tion.Model2 was then compared with original models(Model0 group)in three dimensions,evaluating reconstruction accuracy through root mean square(RMS).Reconstruction parameters were optimized to enable automatic matching of Model2 with Model0,facilitating precise digital transfer of screw paths.In clinical application,this method was utilized to produce digital short-segment drilling guides,assisting in the reduction surgery of three mandibular fracture patients.Results Model2 demonstrated automatic matching with Model0,exhibiting detailed surface characteristics and clear screw path position and orientation information.The RMS was measured at(0.32±0.09)mm.Utilization of digital segmented screw path transfer guides assisted in the satisfactory reduction surgery of three pa-tients with comminuted mandibular fractures.Conclusion CBCT scanning of FDM-printed preoperative models accurately captures screw path position and orientation information,enabling digital transfer of screw paths and providing a novel method for precise design of digital surgical guides.

Objective To scan and accurately reconstruct mandible models printed via fused deposition modeling(FDM)that contain screw path information,using cone-beam CT(CBCT),to achieve the digital transfer of preoperative model screw paths.Methods CBCT scans were conducted on 12 FDM-printed mandibular models(Model1 group)intended for prebending reconstruction plates.Mim-ics software was employed to reconstruct scanned data into mandibular models(Model2 group)and extract digital screw path informa-tion.Model2 was then compared with original models(Model0 group)in three dimensions,evaluating reconstruction accuracy through root mean square(RMS).Reconstruction parameters were optimized to enable automatic matching of Model2 with Model0,facilitating precise digital transfer of screw paths.In clinical application,this method was utilized to produce digital short-segment drilling guides,assisting in the reduction surgery of three mandibular fracture patients.Results Model2 demonstrated automatic matching with Model0,exhibiting detailed surface characteristics and clear screw path position and orientation information.The RMS was measured at(0.32±0.09)mm.Utilization of digital segmented screw path transfer guides assisted in the satisfactory reduction surgery of three pa-tients with comminuted mandibular fractures.Conclusion CBCT scanning of FDM-printed preoperative models accurately captures screw path position and orientation information,enabling digital transfer of screw paths and providing a novel method for precise design of digital surgical guides.

Objective To analyze the clinical efficacy of AngioJet mechanical thrombus aspiration system for patients with acute pulmonary embolism (PE).Methods Clinical data of 28 cases of acute pulmonary embolism (PE) patients was retrospectively analyzed,8 cases (AngioJet group) were treated with AngioJet + CDT,20 cases were treated by pigtail catheter thrombolysis(CDT group)alone,the total amount of urokinase,thrombolytic time,related detection index and the occurrence of complications were compared between the two groups.Results The dosage of urokinase in the two groups was (72.5 ± 44.4) × 104U and (169.0 ± 59.3) × 104 U respectively,P ＜ 0.05.The catheter indwelling time was (1.0 ± 0.89) days and (2.65 ± 0.86) days respectively (P ＜ 0.05).There were no statistically significant differences in SBP,PaO2,SpO2 and D-dimer between the two groups before and after operation (P ＞ 0.05).Conclusion Both AngioJet and CDT are effective methods for the treatment of acute PE.The combination of the two methods can accelerate the improvement of clinical symptoms,reducing the dosage of thrombolytic drugs and the occurrence of surgery-related complications.

Hyper-osmotic stress is one of the key factors that decrease the efficiency of biological succinic acid production. To increase the osmotic stress tolerance of succinate-producing Escherichia coli, we studied the influence of IrrE, an exogenous global regulator, on cell osmotic stress resistance. Fermentation results showed that cell growth and succinic acid production by the recombinant increased under different Na+ concentrations. Meanwhile, the maximum dry cell mass, glucose consumption and succinic acid concentration increased 15.6%, 22% and 23%, respectively, when fermented in a 5-L bioreactor. Expressing IrrE improved cell resistance to hyper-osmotic stress. Further comparison of intracellular osmoprotectants (trehalose and glycerol) concentrations showed that trehalose and glycerol concentrations in the recombinant increased. This suggested that introduction of IrrE could enhance intracellular osmoprotectants accumulation which conferred cell with improved resistance to osmotic stress.

Antigens, Neoplasm ; metabolism ; Antigens, Surface ; metabolism ; Colorectal Neoplasms ; immunology ; pathology ; Humans ; Prognosis ; Trophoblasts ; immunology

Objective To investigate the effect of sufentanil postconditioning on myocardial ischemiareperfusion (I/R) injury in patients undergoing cardiac valve replacement under cardiopulmonary bypass (CPB).Methods Sixty ASA Ⅱ or Ⅲ patients ( NYHA Ⅱ or Ⅲ ) of both sexes,aged 19-64 yr,scheduled for cardiac valve rreplacement under CPB,were randomly divided into 4 groups ( n =15 each):control group ( group C),sufentanil 0.5 μg/kg group (group S1 ),sufentanil 1.0 μg/kg group (group S2 ) and sufentanil 2.0 μg/kg group ( group S3 ).In groups S1,S2 and S3,sufentanil 0.5,1.0 and 2.0 μg/kg were infused over 2 min via aortic root 5 min before aortic unclamping respectively.In group C,the equal volume of normal saline (2 ml/kg) was infused instead of sufentanil.Blood samples were taken from the radial artery immediately before induction of anesthesia ( T2 ) and at 2,4,8,24 and 48 h after aortic unclamping ( T1-5 ) for determination of plasma concentrations of cardiac troponin-I (cTnI) and malondialdehyde (MDA) and activities of creatine kinase isoenzyme-MB (CK-MB) and superoxide dismutase (SOD).The duration of CPB,time of aortic clamping,extubation time,duration of stay in ICU,and myocardial contractility score and volume of drainage at 24 h after the operation were recorded.The restoration of spontaneous heart beat and adverse cardiovascular events were observed.Results The plasma cTnI,and MDA concentrations and CK-MB activity were significantly lower,while the SOD activity was significantly higher at T1-3 in group S1 than in group C ( P ＜ 0.05).The plasma cTnl concentration and CK-MB activity were significantly lower at T1-5,the plasma MDA concentration was significantly lower at T1-4,and SOD activity was significantly higher at T1-4,the extubation time and duration of stay in ICU were significantly shorter,and the myocardial contractility score at 24 h after the operation and incidence of adverse cardiovascular events were significantly lower in groups S2,3 than in group C ( P ＜ 0.05),The plasma cTnl concentration and CK-MB activity were significantly lower at T4,5,The plasma MDA concentration was significantly lower at T4,the SOD activity was significantly higher at T3,4,and the myocardial contractility score at 24 h after the operation was significantly lower in groups S2,3 than in group S1 ( P ＜ 0.05).Conclusion Sufentanil postconditioning can relieve myocardial I/R injury in patients undergoing cardiac valve replacement under CPB,and the mechanism is related to inhibition of lipid peroxidation.

OBJECTIVETo evaluate the role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and plasma homocysteine levels in Chinese patients with type 2 diabetes mellitus and diabetic retinopathy (DR).

METHODSMTHFR genetic C677T polymorphisms were determined by PCR-restriction fragment length polymorphism. Total plasma homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection.

RESULTSThe frequencies of MTHFR T homogenetic type and CT heterogenetic type and allele T (28.18%, 41.82%, 49.09%) in type 2 diabetic patients with diabetic retinopathy were significantly higher than those in diabetic patients without retinopathy (18.37%,29.59%,33.16%) or the normal controls (17.54%, 28.07%, 31.58%). Howerver, there were no significant differences in the frequency of MTHFR genotype and allele between the type 2 diabetic patients without retinopathy and the normal controls. The presence of T allele appeared to have a strong association with the development of diabetic retinopathy. The odds ratio was 1.94 and the 95% confidence interval was 1.31-2.88. Moreover, the plasma homocysteine levels in patients with TT or CT genotype were markedly higher than those in patients with CC genotype.

CONCLUSIONMTHFR gene C677T mutation associated with a predisposition to increase of plasma homocysteine may represent a genetic risk factor for diabetic retinopathy in Chinese type 2 diabetes mellitus.

Adult ; Alleles ; DNA ; genetics ; metabolism ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; complications ; genetics ; Diabetic Retinopathy ; blood ; etiology ; genetics ; Female ; Gene Frequency ; Genotype ; Homocysteine ; blood ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; Middle Aged ; Oxidoreductases Acting on CH-NH Group Donors ; genetics ; Point Mutation ; Polymorphism, Genetic

AIM　To study the synthesis of zinc chlorin e4 (1), its experimental antigastrelcosis activity as well as the protection against acute liver injuries. METHODS　Chlorin e6 (3) was prepared through acidic and alkaline oxidative degradation using silkworm excrement crude chlorophyll extracts as starting material. Compound 1 was synthesized via Zn(OAc)2 complex action with Chlorin e4 (2) which was prepared by refluxing 3 in pyridine. Gastric ulcers were induced by abdominal injection of 0.2% indomethacin at 20 mg.kg-1 in rats. The ulcer indexes and ulcer numbers in gastric mucosa were determined. Acute liver injuries were induced by abdominal injection of 0.3% thioacetamide (TAA) or 0.3% CCl4 at 20 mg.kg-1 in mice, and activities of SGPT in mice were determined. RESULTS　Compound 1 is previously unknown. Compared with control group, abdominal administration of 1 at 100 mg.kg-1 reduced significantly the gastric ulcer index (P<0.001) and the number of ulcer (P<0.001) induced by indomethacin in rats. Abdominal administration of 1 at 100 mg.kg-1×3 exhibited marked inhibitory effects on elevated activities of SGPT induced by TAA (P<0.02) or CCl4 (P<0.01) in mice. CONCLUSION　These results show that 1 has significant protective effect against indomethacin-induced gastric lesion in rats and TAA or CCl4 induced acute liver injuries in mice. It is suggested that 1 may be a promising new drug candidate for antigastrelcosis and liver injury protection.