ObjectiveTo investigate the positive rate of thyroid peroxidase antibody(TPO-Ab) in the diabetic in-patients. MethodsThe positive rates of thyroid peroxidase antibody ( TPO-Ab ) was measured in 1884 subjects, including 1508 type 2 diabetes mellitus ( T2DM ), 76 classic typetype 1 diabeties( T1 DM ), 44 latent autoimmune diabetes in adults (LADA) and 256 "untype" diabetics ( NTDM ). Clinical data were registered and analyzed. Results( 1 )The positive rates of TPO-Ab were 14. 59％ in T2DM(220/1508) ,42. 11％ in T1DM (32/76) ,31.25％ in NTDM ( 80/256 ), 63.64％ in LADA group ( 28/44 ), respectively. The positive rate of T2DM was significantly lower than that of LADA ( P ＜ 0. 05 ), but no significant difference was found in the coparison between T1 DM and NTDM ( P ＞ 0. 05 ). ( 2 ) There were no significant differences between LADA and NTDM groups in the comparison of age, course of disease and BMI ( Ps ＞ 0. 05 ). Conclusion①The positive rate of TPO-Ab in NTDM was significantly higher than that of T2DM, whereas significantly lower than that of T1 DM and LADA.②The positive rate of TPO-Ab was highest in LADA, which indicate that LADA and AIT might have the common etiological mechanisms. ③There is a consisted increasing trend in the positive rate of TPO-Ab from T2DM ,NTDM,and classic T1DM to LADA.

Aim To construct 3 D structure model of cardiac Cav1.2 channel and check its accuracy and re-liability.Methods Homology model of Cav1.2 chan-nel α1 subunit was constructed using SWISS-MODEL server.The model was submitted to an online testing server built by University of California and scored by it.The binding of Cav1.2 channel with blocker or drug was simulated by MOE software molecular docking pro-gram to check the model′s accuracy and reliability.Re-sults Both the target sequence Cav1.2 α1 C and the template sequence Cav1.1 α1 S searched by SWISS-MODEL server belonged to L-type Ca2+channel.Since the homology was 7 1.5% revealed by sequence align-ment,homology modeling was performed using automa-ted mode.L-type Ca2+ channel blockers Verapamil, Nifedipine and Diltiazem could bind to the 3 D structure model of Cav1.2 channel,while sodium channel bloc-ker TTX could not.Furthermore,active ingredient of traditional Chinese drug Praeruptorin A and Berberine could also bind to the 3D structure model of Cav1.2 channel.Conclusion The 3 D structure model of Cav1.2 channel was constructed successfully,which provides reliable materials for further studies and estab-lishes the foundation for the application of homology modeling in the study of 3 D structure prediction of ion channels.

OBJECTIVE: To study the expression of high-mobility group box 1 (HMGB1) in neonates with sepsis and its role in the pathogenesis of neonatal sepsis. METHODS: A total of 62 neonates with sepsis were enrolled as the sepsis group, 66 neonates with local infection were enrolled as the local infection group, and 70 healthy neonates were enrolled as the healthy control group. Serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17 (IL-17), interleukin-23 (IL-23), C-reactive protein (CRP) and procalcitonin (PCT) were measured. The mRNA expression of HMGB1, Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) and the protein expression of TLR4 and NF-κB in peripheral blood mononuclear cells (PBMCs) were also measured. PBMCs from healthy neonates were divided into 4 groups: control, HMGB1 treatment, HMGB1+TAK-242 (a TLR4 inhibitor) treatment and HMGB1+PDTC (an NF-κB inhibitor) treatment, and the mRNA expression of TLR4, NF-κB and IL-8 and the protein expression of TLR4 and NF-κB were measured. PBMCs from healthy neonates were divided into another 3 groups: control, LPS treatment and LPS+glycyrrhizin (an HMGB1 inhibitor) treatment, and the mRNA expression of HMGB1, TLR4, NF-κB and IL-8 and the protein expression of TLR4 and NF-κB were measured. RESULTS: Compared with the local infection and healthy control groups, the sepsis group had significantly higher serum levels of IL-6, IL-8, IL-17, IL-23, CRP and PCT (P<0.05), as well as significantly higher mRNA expression of HMGB1, TLR4 and NF-κB and protein expression of TLR4 and NF-κB in PBMCs (P<0.05). HMGB1 significantly induced the mRNA and protein expression of TLR4 and NF-κB in PBMCs (P<0.05). TAK-242 inhibited the mRNA and protein expression of TLR4 and NF-κB and mRNA expression of IL-8 (P<0.05). PDTC inhibited the mRNA and protein expression of NF-κB and the mRNA expression of IL-8 (P<0.05). LPS significantly induced the mRNA expression of HMGB1 and the mRNA and protein expression of TLR4 and NF-κB and then stimulated the mRNA expression of IL-8 (P<0.05). Glycyrrhizin inhibited the mRNA expression of HMGB1 and the mRNA and protein expression of TLR4 and NF-κB and then reduced the mRNA expression of IL-8 (P<0.05). CONCLUSIONS HMGB1 plays an important role in the pathogenesis of neonatal sepsis by activating the TLR4/NF-κB signaling pathway and inducing the secretion of inflammatory factors including IL-8. The HMGB1 blocker glycyrrhizin can inhibit activation of the TLR4/NF-κB signaling pathway and the secretion of inflammatory factors.
HMGB1 Protein ; genetics ; Humans ; Infant, Newborn ; Leukocytes, Mononuclear ; NF-kappa B ; Sepsis ; genetics ; Signal Transduction

Limitations of polyacrylamide gel or agarose gel electrophoretic methods in genotyping research affect the interpreting of detection results. In order to develop a simple and reliable method for appraising results of ABO genotyping detection, the microfluidic chip analysis system was established by using microfluidic chip to replace the gel electrophoresis and combining with multiplex-PCR-RFLP technique. 150 blood samples were tested by this microfluidic chip analysis system with multiplex-PCR-RFLP technique to evaluate its stability and accuracy. The results showed that all the testing results were consistent with serologic ABO genotyping results and 1 blood sample with decrease of B antigen caused by CML was identified. In conclusion, the established microfluidic chip analysis system is stable and reliable technique. Application of this technique enables the ABO genotyping results to be more objective and accurate.
ABO Blood-Group System ; genetics ; Blood Grouping and Crossmatching ; methods ; DNA Primers ; genetics ; Genotype ; Humans ; Microfluidic Analytical Techniques ; Microfluidics ; Oligonucleotide Array Sequence Analysis

Objective: To analyze CYP2C9 and VKORC1 gene polymorphisms in Chinese Han population and their correlation with the maintenance dosage of warfarin. Methods: From October 2017 to April 2018, 458 Chinese Han patients (213 males and 245 females, aged from 26 to 94 years old) who underwent coagulation analysis in Peking University People′s Hospital were included in this retrospective study. PCR-Fluorescent probe method was applied to detect CYP2C9*3 and VKORC1-1639A>G gene polymorphisms in 458 patients, and among them, 130 patients who took warfarin for anticoagulant therapy and reached the international standard ratio of prothrombin time (INR) within the range of 2.0-3.0 were recorded. The basic information, dosage of warfarin and INR were also recorded. The statistical analysis data were compared with the reference table of recommended dosage of warfarin for different genotypes of patients recommended by FDA and the formula of predicted dosage of warfarin was simply verified by SPSS. Results: Among the 458 patients who took anticoagulant therapy, the genotype frequencies of CYP2C9*1/*1(AA), CYP2C9*1/*3(AC) and CYP2C9*3/*3(CC) were 90.8%, 8.5%, and 0.7%; the genotype frequencies of VKORC1-1639GG and VKORC1-1639AG were 0.9% and 14.2%; the genotype frequencies of VKORC1-1639AA was 84.9%. After INR was reached, the results showed that the variant CYP2C9*1/*3 and CYP2C9*3/*3 required lower daily maintain dosage [(2.92±1.29) mg] than wild-type CYP2C9*1/*1 patients did [(3.91±1.63) mg], with statistically significant difference (P=0.018). And variant VKORC1-AA required lower daily maintain dosage [(3.68±1.64) mg] than variant VKORC1-AG patients did [(4.54±1.29) mg], with statistically significant difference (P=0.001). The application dosage of warfarin in patients with different VKORC1+CYP2C9 genotypes was consistent with the recommended dosage of the FDA reference table. The prediction accuracy of miao 2007 formula was lower than that of IWPC formula, and 94.1% of patients′ dosages of warfarin were underestimated. Conclusion Patients with CYP2C9*3 or VKORC1-AA genotype required lower warfarin dosage. The CYP2C9 and VKORC1 gene polymorphisms had a certain correlation with maintenance dosage of warfarin.

OBJECTIVETo investigate the effects of alveolar bone resorption on stress of tooth/implant-supported restoration connected by precision attachment using three-dimensional finite element(FEM) approach.

METHODSThe FEM was applied to analyze the stress distribution of tooth/implant-supported restoration connected by precision attachment under various loading conditions when the alveolar bone was absorbed to different level.

RESULTSThe stress values of the tooth, implant and their surrounding bone increased when their surrounding bone decreased by bone absorption.

CONCLUSIONThe stress values of the tooth, implant and their surrounding bone were closely related with the bone resorption.

[Objective]To explore the correlations between different indices of lipoprotein cholesterol and apolipopro-tein of coronary heart disease(CHD)patients,especially that between low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)and that between apolipoprotein A1(apoA1)and apolipoprotein B100 (apoB100),as well as the correlations between these indices,indices ratios and the severity of coronary artery lesion.[Methods]301 coronary heart disease patients hospitalized to accept percutaneous coronary intervention(PCI)in the Third Affiliated Hospital of Sun Yat-sen University during 2013-2014 were recruited in the study. Fasting serum lipid indices including triglycerides(TG),total cholesterol(TC),LDL-C,HDL-C,apoA1 and apoB100 were examined before surgery.Gensini score was calculated to evaluate the severity of coronary artery lesion. 153 patients whose Gensini score was less than 50 were assigned to Group A,while 148 patients with Gensini score greater than or equal 50 were distributed to Group B.[Results]Positive correlations were found between LDL-C and HDL-C(r=0.161,P=0.005), apoA1 and apoB100(r=0.358,P<0.001),apoB100 and LDL-C(r=0.487,P<0.001),apoA1 and LDL-C(r=0.178, P=0.002)by linear correlation analysis. No significant correlation was found between apoB100 and HDL-C. None of LDL-C,HDL-C,TC was correlated with Gensini score. However,LDL-C/HDL-C ratio was positively correlated with Gensini score(r=0.148,P=0.01). The results showed no significant correlations between apoB100,apoB100/apo A1 ratio and Gensini score but negative correlation between apoA1 and Gensini score(r=-0.129,P=0.025). The positive correlation between HDL-C/LDL-C ratio and Gensini score was still valid after multi-factors adjustment (β=5.071,P=0.018).[Conclusion]Of patients with coronary heart disease,there exist some correlations between LDL-C and HDL-C,apoA1 and apoB100,while the correlation between LDL-C and HDL-C is relatively weak.The LDL-C/HDL-C ratio,weakly positively correlated with the severity of coronary artery lesion,is a risk factor of coronary artery lesion,while the level of apoA1,negatively correlated with the severity of coronary artery lesion,could play a protective role.

Introduction:Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer. This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the TNM staging system and therapeutic regimens in patients with nasopharyngeal carcinoma (NPC). Methods:A total of 2,626 patients with NPC were retrospectively analyzed. Platelet count>300 × 109/L was defined as thrombocytosis. Matched-pair analysis was performed between patients receiving chemoradiotherapy and radiotherapy. Results:Multivariate analysis showed that platelet count was an independent unfavorable prognostic factor for overal survival (OS) [hazard ratio (HR)=1.810, 95%confidence interval (CI)=1.531–2.140, P<0.001] and distant metastasis–free survival (DMFS) (HR=1.873, 95%CI=1.475–2.379, P<0.001) in the entire patient cohort. Further subgroup analysis revealed that increased platelet count was an independent unfavorable prognostic factor for OS and DMFS in patients with NPC stratified by early and advanced T category, N category, or TNM classification (al P≤0.001). Receiver operating characteristic (ROC) curves verified that the predictive value of TNM classification for OS was improved when combined with pretreatment platelet count (P=0.030). Matched-pair analysis showed that chemoradiotherapy significantly improved OS only in advanced-stage NPC with thrombocytosis (HR=0.416, 95%CI=0.226–0.765, P=0.005). Conclusions:Pretreatment platelet count, when combined with TNM classification, is a useful indicator for metastasis and survival in patients with NPC. It may improve the predictive value of the TNM classification and help to identify patients likely to benefit from more aggressive therapeutic regimens.

This study established an efficient and specific method for type analysis of genetic variants of Balantioides coli.The restriction endonucleases ApoI and PflMI were selected to digest the PCR amplification products of ITS1-5.8S rDNA-ITS2 of B.coli,and to establish a PCR-RFLP typing method.The PCR-RFLP method was subsequently used to analyze the genetic variants in clinical fecal samples from pigs,sheep,and guinea pigs.The PCR-RFLP method based on ApoI and PflMI accurately distinguished the main A and B genetic variants of B.coli,and further divided the main B type into B-c and B-t sub-types of genetic variants with PflMI.Compared with the results of microscopy and sequencing,the PCR-RFLP method showed good specificity and higher sensitivity,and was able to identify not only single but also multiple variants of B.coli in a single clinical sample.This study successfully established the PCR-RFLP method for B.coli,which can be used for genetic di-versity identification and molecular epidemiological studies of B.coli.

Objective:To investigate the spectrum and antimicrobial resistance of major pathogens causing nosocomial infections in China during 2020-2021.Methods:A total of 1 311 non-duplicated nosocomial pathogens causing bloodstream infections (BSI, n=670), hospital-acquired pneumonia (HAP, n=394) and intra-abdominal infections (IAI, n=297) were collected from 10 teaching hospitals across China. The minimum inhibitory concentrations (MICs) of clinical common strains were determined using agar dilution or broth microdilution method. Interpretation of reults followed the CLSI M100-Ed33 criteria, with data analysis conducted using WHONET-5.6 software. The Chi-square test was used to compare rates. Results:The most prevalent pathogens causing BSI were Escherichia coli (21.2%, 142/670), Klebsiella pneumoniae (14.9%, 100/670) and Staphylococcus aureus (11.5%, 77/670); the most prevalent pathogens causing HAP were K. pneumoniae (27.7%, 109/394), Acinetobacter baumanii (22.1%, 87/394) and Pseudomonas aeruginosa (18.3%, 72/394). IN IAI, E. coli (24.3%, 60/247), Enterococcus faecium and K. pneumoniae (both 14.6%, 36/247) were dominated. All S. aureus strains were susceptible to tigecycline, linezolid, daptomycin and glycopeptides. Rates of methicillin-resistant S. aureus (MRSA) and coagulase-negative Staphylococcus (MRCNS) were 36.5% (42/115) and 74.5% (38/51), respectively. The rate of vancomycin-resistant E. faecium and E. faecalis was 3.3% (3/90) and 1.9% (1/53), respectively. The prevalence of extended-spectrum β-lactamase (ESBL) was 23.7% (58/245) in K. pneumonia and 60.5% (130/215) in E. coli.The rate of carbapenem-resistant K. pneumonia and E. coli was 29.8% (73/245) and 4.2% (9/215), respectively; the percentage of tigecycline-resistant K. pneumonia and E. coli was 1.6% (4/245) and 0, respectively; the rate of colistin-resistant K. pneumonia and E. coli was 1.6% (4/245) and 2.8% (6/215), respectively; the percentage of ceftazidime/avibactam-resistant K. pneumonia and E. coli was 2.0% (5/245) and 2.3% (5/215), respectively. The rate of carbapenem-resistant A. baumanii and P. aeruginosa was 76.7% (125/163) and 28.4% (33/116), respectively. A. baumanii showed low susceptibility to most antimicrobial agents except colistin (98.8%, 161/163) and tigecycline (89.6%, 146/163). Colistin, amikacin and ceftazidime/avibactam demonstrated high antibacterial activity against P. aeruginosa with susceptility rates of 99.1% (115/116), 94.0% (109/116) and 83.6% (97/116), respectively. Conclusions:The major pathogens of nosocomial infections were K. pneumonia, E. coli, A. baumanii, P. aeruginosa and S. aureus. Nosocomial Gram-negative pathogens exhibited high susceptibilities to tigecycline, colistin and ceftazidime/avibactam. Antimicrobial resistance in A. baumannii remains a significant challenge. The increasing prevalence of carbapenem-resistant Enterobacterales underscores the urgency of antibiotics rational applications and hospital infection controls.