Objective To explore the safety and efficacy of sequential tirofiban in patients with small artery occlusion(SAO)cerebral infarction after intravenous thrombolysis.Methods A retrospective collection of 90 cases of small artery occlable cerebral infarction who underwent intravenous thrombolytic treatment within the time window at the Department of Neurology,Heji Hospital,Affiliated to Changzhi Medical College from December 2019 to June 2022.It was divided into observation group(receiving tirofiban,conventional antiplatelet aggregation,lipid regulation and stabilization)and control group(conventional antiplatelet aggregation,lipid regulation and plaque stabilization).Baseline feature differences were balanced by propensity score matchingd.The main evaluation index was the long-term prognosis,the ratio of good prognosis(mRS≤2 points)at 3 months.The secondary outcome was early neurological impairment and clinical outcome.Results At 3 months,the long-term functional outcome of the tirofiban group was better than that of the control group(P>0.05).Compared with the control group,the early neurological function NIHSS score of the tirofiban group was significantly reduced(P<0.05).On the 7th day,the total efficiency of tirofiban treatment was higher than that of the control group(P<0.05).On the 14th day,the data was still significantly higher(P<0.05).Conclusion Sequential tirofiban treatment after thrombolysis is safe and effective for SAO,which may be the remedial treatment of AIS patients after thrombolysis and recanalization.

Objective:To evaluate the effects of quality improvement (QI) program on the incidence of bronchopulmonary dysplasia (BPD) in very preterm infants (VPIs) [gestational age (GA)<32 weeks].Methods:From July to December 2017,VPIs admitted to the Department of Neonatology of Yancheng Maternity and Child Health Care Hospital were retrospectively enrolled and were assigned into pre-quality improvement program group (Pre-QI group).From July to December 2018, VPIs were assigned into post-quality improvement program group (Post-QI group). QI program included delayed umbilical cord clamping (DCC), early postnatal nasal continuous positive airway pressure ventilation (nCPAP) and minimally invasive pulmonary surfactant therapy (MIST). The clinical data and prognostic indicators of the two groups of VPIs and their mothers were compared. Independent sample t-test or continuity-adjusted Chi-square test (or Fisher's exact test) and Logistic regression were used for statistical analysis. Results:A total of 204 VPIs were enrolled, including 96 cases in Pre-QI group and 108 cases in Post-QI group. 1 min Apgar score and hematocrit on admission to the neonatal intensive care unit (NICU) in the Post-QI group were significantly higher than the Pre-QI group( P<0.05). The incidence of delivery room resuscitation, endotracheal intubation at birth and endotracheal intubation in NICU in the Post-QI group were significantly lower than the Pre-QI group( P<0.05). The application of pulmonary surfactant and mechanical ventilation, the incidence of neonatal respiratory distress syndrome and BPD in the Post-QI group were lower than the Pre-QI group ( P<0.05). After adjusting for confounding factors, Logistic regression analysis showed that DCC ( aOR=0.261,95% CI 0.091~0.718, P=0.023), nCPAP ( aOR=0.284,95% CI 0.123~0.667, P=0.015), MIST ( aOR=0.276,95% CI 0.114~0.627, P=0.011) were protective factors of BPD, and MV ( aOR=2.023,95% CI 1.048~3.918, P=0.036) was risk factor of BPD. Conclusions:The QI program consisting of DCC, early nCPAP and MIST for VPIs can reduce the incidence of BPD.

ObjectiveTo explore the anti-abortional effect of Pangshi Antai Zhixue decoction and its mechanism in helper T lymphocyte 1 （Th1）/Th2 balance in the decidual tissues of spontaneous abortion rats with heat syndrome， based on the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodAconiti Lateralis Radix Praeparata， Zingiberis Rhizoma， and Cinnamomi Cortex decoction was used to replicate the rat model of spontaneous abortion with heat syndrome. The spontaneous abortion rats with heat syndrome were randomly divided into model group， aspirin group （5.25 mg·kg^-1）， dydrogesterone group （3.02 mg·kg^-1）， Pangshi Antai Zhixue decoction high-dose （44 g·kg^-1）， medium-dose （22 g·kg^-1）， and low-dose （11 g·kg^-1） groups， with ten rats in each group. Ten normal rats were divided into a normal group. Rats in each group were given corresponding drugs， Once a day for 12 d. After 24 h of the last administration， blood was collected from the abdominal aorta. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of β-human chorionic gonadotropin （β-HCG）， progesterone （P）， estradiol （E₂）， γ interferon （IFN-γ）， and interleukin-4 （IL-4） in rat serum. The uterus and meconium tissues of rats were collected to determine the number and rate of miscarriages. Western blot was used to detect GATA3， T-bet， p38 MAPK， and its phosphorylation in the decidual tissue. ResultAs compared with the normal group， the number of live births， the β-HCG， P， E₂， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the model group were reduced （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 MAPK and T-bet protein levels in the demolded tissues increased （P<0.01）. As compared with the model group， the number of live births， the β-HCG， P， E₂， and IL-4 in the serum， and the GATA3 protein expression in the decidual tissue in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， whereas the number and rate of miscarriages， IFN-γ in the serum， and the expression of p-p38 and T-bet protein levels in the demolded tissues reduced （P<0.01）. As compared with the aspirin group， the P， E₂， and IL-4 in the serum of rats in the dydrogesterone group and the Pangshi Antai Zhixue decoction high-dose and medium-dose groups increased （P<0.01）， the number of live births in the Pangshi Antai Zhixue decoction medium-dose group increased （P<0.01）， and the β-HCG and IFN-γ in the serum of rats in the dydrogesterone group decreased （P<0.01）. The number and rate of miscarriages， IFN-γ in the serum， and T-bet and GATA3 levels in the decidual tissues of rats in the Pangshi Antai Zhixue decoction medium-dose group decreased （P<0.05）. Compared with the Pangshi Antai Zhixue decoction medium-dose group， the low-dose group， high-dose group， and dydrogesterone group showed increased number and rate of miscarriages （P<0.05）， and the high-dose group and dydrogesterone group decreased the number of live birth （P<0.01）. The IFN-γ in the serum and p-p38 MAPK and T-bet protein in the decidual tissue in the low-dose group， and the p-p38 MAPK and T-bet protein in the decidual tissue in the high-dose group all increased （P<0.05）. The β-HCG， P， and E₂ in the serum of rats in the Pangshi Antai Zhixue decoction low-dose group， dydrogesterone group， and aspirin group decreased （P<0.01）， and the IL-4 in the serum and GATA3 in the decidual tissue of rats in the Pangshi Antai Zhixue decoction low-dose and high-dose group and the dydrogesterone group decreased （P<0.01）. ConclusionPangshi Antai Zhixue decoction realizes the effect of fetal protection by regulating the activation of p38 MAPK signal pathways and Th1/Th2 balance.

Klebsiella pneumoniae(K.pneumoniae)is an important pathogen that can cause severe hospital-and community-acquired infections.To systematically investigate its methylation features,we determined the whole-genome sequences of 14 K.pneumoniae strains covering varying serotypes,multilocus sequence types,clonal groups,viscosity/virulence,and drug resistance.Their methy-lomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies.We identified 15 methylation motifs[13 N6-methyladenine(6mA)and two 5-methylcytosine(5mC)motifs],among which eight were novel.Their corresponding DNA methyl-transferases were also validated.Additionally,we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains,and identified differential distribution pat-terns of some hemi-/un-methylated GATC motifs,which tend to be located within intergenic regions(IGRs).Specifically,we characterized the in vivo methylation kinetics at single-base resolu-tion on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation.The slow methylation of the GATC motifs in the replication origin(oriC)regions and IGRs implicates the epigenetic regulation of replication initiation and transcription.Our findings illustrate the first comprehensive dynamic methylome map of K.pneumoniae at single-base resolution,and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.

目的：分析Claudin-2蛋白在食管鳞癌（esophageal squamous cell carcinomas，ESCC）组织中的表达及其与患者临床病理特征、5年生存率的关系，探索其对ESCC细胞KYSE450的增殖、迁移和侵袭的影响。方法：选取河南省肿瘤医院2010至2013年间初治的ESCC患者手术切除肿瘤组织52例及其中20例对应的癌旁组织标本，采用免疫组化和WB法检测Claudin-2的表达并分析其与患者临床病理特征和5年生存率的关系。WB法检测ESCC细胞（KYSE450、KYSE150、KYSE510、KYSE140）和人永生化食管上皮细胞SHEE中Claudin-2的表达，构建Claudin-2 shRNA慢病毒载体并转染KYSE450细胞构建敲低Claudin-2表达的细胞系，进一步通过克隆形成实验、细胞划痕实验及Transwell实验检测敲低Claudin-2对KYSE450细胞增殖、迁移和侵袭的影响。结果：ESCC组织中Claudin-2阳性率显著高于癌旁组织（P<0.05），ESCC组织中Claudin-2的表达与淋巴结转移有关（P<0.05）。Claudin-2表达阳性患者5年生存率显著低于阴性者（P<0.05）。成功构建敲低Claudin-2表达的KYSE450细胞系。sh-Claudin-2组细胞的克隆形成数、伤口愈合率和侵袭细胞数均显著低于sh-NT组和对照组（P<0.05）。结论：ESCC组织中Claudin-2的表达高于癌旁组织，且与患者5年生存率呈负相关，Claudin-2能够增强KYSE450细胞的增殖、迁移和侵袭能力。

Objective:To explore the performance of the commonly used whole blood C-reactive protein (CRP) detection systems and give related recommendation on the performance requirements of detection systems.Methods:A total of 7 540 venous blood samples from 26 maternal, child and children′s hospitals were collected to conduct this multi-center study on the analytical performance of 5 commonly used whole blood CRP detection systems from March to April in 2019. The blank check, carryover, repeatability, intermediate precision, linearity, sample stability, influence of hematocrit/triglyceride/bilirubin, comparison with SIEMENS specific protein analyzer and trueness were evaluated. The 5 systems included BC-5390CRP autohematology analyzer, AstepPLUS specific protein analyzer, Ottoman-1000 Automated Specific Protein POCT Workstation, i-CHROMA Immunofluorometer equipment Reader and Orion QuikRead go detecting instrument. The 5 systems were labeled as a, b, c, d and e randomly.Results:Within the 5 systems, all values of blank check were less than 1.00 mg/L, the carryovers were lower than 1.00%. The repeatability of different ranges of CRP concentrations including 3.00-10.00, 10.00-30.00 and>30.00 mg/L were less than 10.00%, 6.00% and 5.00%, respectively, and the intermediate precision was less than 10.00%. The linearity correlation coefficients of the 5 systems were all above 0.975, while the slope was within 0.950-1.050. Whole blood samples were stable within 72 hours both at room temperature (18-25 ℃) and refrigerated temperature (2-8 ℃). The CRP results were rarely influenced by high triglyceride or bilirubin, except for the immmunoturbidimetric test based on microparticles coated with anti-human CRP F(ab) 2 fragments. When triglyceride was less than 15.46 mmol/L, the deviation of CRP was less than 10.00%. When bilirubin was less than 345.47 μmol/L, the deviation of CRP was less than 10.00%. CRP was more susceptible to Hct on the systems without Hct correction. The deviation of CRP between different Hct dilution concentration and 40% dilution concentration can reach as high as 67.48%. The correlation coefficients ( r) of 5 systems were all more than 0.975 in the range of 0-300.00 mg/L compared with Siemens specific protein analyzer. All systems passed the trueness verification using the samples with specified values of 12.89 and 30.60 mg/L. Conclusion:The performance of 5 systems can basically meet the clinical needs, but it is suggested that the whole blood CRP detection system without automatic Hct correction should be modified manually.

TORCH, which is considered as a series of pathogens, including the Toxoplasma gondii, Rubella virus, Cytomegalovirus or Herpes simplex virus, often infects the pregnant women to induce the the fetus or newborn infection by transplacental infection or exposure to contaminated genital tract secretions at delivery. Increasing evidence have been confirmed that the infection of TORCH may cause the miscarriage, premature birth, malformed fetus, stillbirth, intrauterine growth retardation, neonatal multiple organ dysfunction and other adverse pregnancy outcomes. For most TORCH-infections cases may lacking the effective treatments during pregnancy, and it is important to achieve the effacing monitoring of TORCH infections before and during pregnancy. The laboratory testing of TORCH has the great significance. However, the consensus opinions still need to improve the the standardization of TORCH testing process and the correct interpretation. Based on the characteristics of the TORCH detection method, this article gives a consensus opinion on the standardized detection and clinical application of TORCH from the laboratory perspective according to the characteristics and types of infection of different pathogens.

Objective To obtain a non-invasive subclinical hypothyroidism ( SCH) mouse model, and to explore microRNAs profile related to lipid metabolism in the model mice. Methods C57BL/6 male mice (8 weeks) were treated with methimazole ( MMI, 0. 08 mg/kg BW/d) to construct SCH mouse model. MicroRNAs profiling analysis was performed by real-time quantitative polymerase chain reaction ( qRT-PCR) . Results Compared with the control group, the serum thyroid stimulating hormone ( TSH ) in subclinical hypothyroidism group increased significantly (P>0.01), while the serum free thyroxine(FT4) level did not show significant difference between the two groups (P>0. 05), which was in line with the diagnostic criteria of SCH. SCH mice was accompanied by dyslipidemia and liver lipid metabolism disorders. Four lipid metabolism related miRNAs, miR-33, miR-122, miR-199a-5p, and miR-375 in the liver of SCH mice were significantly decreased compared with those of control ( P>0. 05). Conclusion The noninvasive SCH model generated by MMI and miRNAs profile provide an animal model and a molecular basis for the study of SCH related lipid metabolism disorders.

OBJECTIVE:To observe therapeutic efficacy and safety of paroxetine combined with flupentixol melitracen in the treatment of post-stroke major depressive disorder(PSMDD). METHODS:120 PSMDD patients were randomly divided into group A(40 cases),group B(40 cases)and group C(40 cases). All patients received routine stroke treatment;group A was additionally given Paroxetine hydrochloride enteric-coated sustained-release tablet 25 mg orally,once a day;group B was additionally given Flu-pentixol melitracen tablet 20 mg orally twice a day;group C was additionally given Paroxetine hydrochloride enteric-coated sus-tained-release tablet (same usage and dosage as group A)+flupentixol melitracen (same usage and dosage as group B). Three groups were treated for 28 d. Clinical efficacies of 3 groups were observed as well as NIHSS,ADL,HADM,SS-QOL score,hos-pitalization stay and the occurrence of ADR. RESULTS:Total response rate of group C was significantly higher than those of group A and B;hospitalization day was significantly less than those of group A and B,with statistical significance(P<0.05);there was no statistical significance between group A and B(P>0.05). There was no statistical significance in the incidence of ADR among 3 groups (P>0.05). Before treatment,there was no statistical significance in NIHSS,ADL,HADM,SS-QOL score among 3 groups(P>0.05). After 10,28 d of treatment,NIHSS,HADM,SS-QOL score of 3 groups were significantly lower than before, above indexes were decreased gradually as time,and the group C were lower than the group A and B;ADL score of 3 groups were significantly higher than before,this index was increased gradually as time,and the group C were lower than the group A and B with statistical significance (P<0.05);there was no statistical significance between group A and B (P>0.05). CONCLUSIONS:Based on routine treatment,paroxetine combined with flupentixol melitracen in the treatment of PSMDD can relieve neurologic function injury,improve depression condition and the quality of life without increasing the occurrence of ADR.

Objective To evaluate the effective and safety of ultrasound-guided percutaneous portal vein guide wire placement adjunct to thrombolytic catheter,which treating portal vein thrombosis after liver transplantation.Methods From Jan 2012 to Dec 2015,a total of 6 patients (5 male,1 female,average age 50.6 years old,age range 41-65 years old) with portal vein thrombosis after liver transplantation were retrospectively studied.The diagnosis was confirmed by contrast enhanced ultrasound (CEUS) with hypoechonic and no enhancement in portal vein.With ultrasound-guided a 18-guage guide wire was placed in right branch of portal vein,and a guidewire was placement.After exchanging the catheter,the thrombosis was confirmed again by venography.A thrombolytic catheter was placed and local thrombolysis therapy was performed.Results The guidewires were successfully placed in 6 patients.The thrombolytic catheters were successfully placed in 5 patients (day 2-60 after operation),and failed in 1 patient (9 years after operation).With 5-11 days urokinase injection,the patency of portal vein was found in 5 patients,of which 4 patients was treated by angioplasty and stent placement.With 16-31 months follow-up,the patency of portal vein was maintained.Neither server complication nor related-death was occurred.Conclusions Ultrasound-guided percutaneous portal vein guide wire placement adjuncts thrombolytic catheter is effective and safety for treating portal vein thrombosis after liver transplantation.