Objective To determine the effect of thrombus aspiration combined with intracoronary injection of recombinant human TNK tissue type plasminogen activator(rhTNK-tPA)on micro-circulation and cardiac function during primary PCI in elderly patients with acute myocardial in-farction(AMI).Methods A retrospective study was conducted on 90 elderly patients with STEMI undergoing primary PCI in Tianjin Third Central Hospital from January 2021 to October 2023.According to their treatment strategies,they were divided into simple suction group(n=46)and combination group(n=44).The suction group received a suction catheter for thrombus aspiration within the coronary artery,while the combined group got a suction catheter for thrombus aspira-tion within the infarct related blood vessels,and then received a local injection of rhTNK-tPA into the lesion through the suction catheter.Their general data,proportion of ST segment resolution(STR)≥70％at 90 min after surgery,postoperative TIMI blood flow grade,postoperative TIMI myocardial perfusion grade(TMPG),corrected TIMI frame count(CTFC)and cardiac ultrasound indicators as well as the incidence of adverse cardiac events during hospitalization were compared between the two groups.Results Larger proportions of postoperative STR ≥70％,postoperative TIMI blood flow grade 3 and TMPG grade 3,and lower CTFC were observed in the combination group than the suction group(P＜0.05).In 1 week after surgery,the simple suction group had lower left ventricular ejection fraction[LVEF,(52.5±6.2)％vs(58.3±6.4)％,P＜0.05],but larger left ventricular diameter(LVD,44.1±3.9 mm vs 51.9±2.5 mm,P＜0.05)than the com-bined group.The incidence of MACE during hospitalization was obviously lower in the combined group than the suction group(20.5％vs 37.0％,P＜0.05).Conclusion Combined intracoronary injection of rhTNK-tPA based on thrombotic aspiration can effectively reduce the coronary thrombus burden,improve myocardial microcirculation perfusion,reduce the incidence of MACE during hospitalization,and not increase the risk of bleeding in elderly STEMI patients.

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.
Humans ; Male ; Animals ; Mice ; Semen/metabolism* ; Dyneins/metabolism* ; Cilia/metabolism* ; Mutation ; Ciliary Motility Disorders/genetics*

Primary ciliary dyskinesia (PCD) is a hereditary disease characterized by airway mucociliary clearance dysfunction. The estimated prevalence of PCD is 1꞉10 000 to 1꞉20 000. The main respiratory manifestations in children are cough, expectoration, chronic rhinitis, sinusitis, and chronic otitis media, while the most common symptoms in adults are chronic sinusitis, bronchiectasis, and infertility. About 50% of patients with certain PCD-related gene variants are combined with situs inversus, and the incidence of congenital heart disease is also high. The pathogenesis behind PCD is that gene variants cause structural or functional disorders of respiratory cilia and motile cilia of other organs, leading to a series of heterogeneous clinical manifestations, which makes it difficult to identify and diagnose PCD. Combining different disease screening tools and understanding the relationship between genotypes and phenotypes may facilitate early diagnosis and treatment for PCD.
Chronic Disease ; Cilia/pathology* ; Humans ; Kartagener Syndrome/genetics* ; Phenotype ; Sinusitis

Objective:The morbidity of malignant melanoma keeps increasing annually.It has high risks of metastasis,drug resistance,and poor prognosis in clinics.Moreover,the available medicines used commonly,such as dacarbazine,temozolomide,the v-Raf murine sarcoma viral oncogene homolog B1(BRAF) inhibitor vemurafenib,and the programmed cell death protein 1 inhibitor pembrolizumab,have some limitations at some extent.Therefore,a more effective therapeutic strategy is still urgently necessary.Methods:In this study,Brucea javanica(L.)Merr.globulins were hydrolyzed with pepsin,then ultra-filtrated to collect small molecular peptides (≤3 kDa).The peptides were then analyzed by anti-proliferative assay,cell-cycle distribution,apoptosis assay,and in vitro wound-scratch assay.Finally,western blotting was conducted to elucidate the underlying anti-melanoma mechanism.Results:The small molecular peptide from B.javanica significantly inhibited malignant melanoma cell proliferation with the IC50 of 2.72 μg/mL for 72 h.Further analysis indicated that B.javanica peptides arrested cell cycle at the S and G2/M phases and induced apoptosis by upregulating p21,p53,Bax,caspase-3,and cleaved PARP while downregulating Bcl-2 expression.The inhibitory migration effects were also confirmed by wound-healing assay.Conclusion:The small molecular biopeptides from B.javanica may be a promising bioactive agent candidate for melanoma treatment.

Objective To summarize CT and MRI features of hyaline vascular type localized Castleman disease(LCD)and analyze the causes of misdiagnosis,to improve the preoperative diagnosis rate.Methods The clinical and imaging data of 7 patients with hyaline vascular type LCD confirmed by operation and pathology were analyzed retrospectively.Results (1)6 cases were misdiagnosed before operation,1 case was misdiagnosed as pancreatic neuroendocrine tumor,1 case as thymoma,1 case as neurogenic tumor,1 case as pheochromocytoma, 1 case as clear cell renal cell carcinoma and 1 case as small mesenteric stromal tumor.(2)1 case was located in the right neck,1 case in the anterior superior mediastinum,1 case in the neck of the pancreas,1 case in the upper part of the left kidney,2 cases in the retroperitoneum and 1 case in the lower abdomen.(3)3 cases were scaned by dynamic enhanced MRI,3 cases were scaned by dynamic enhanced CT, and 1 case was checked by plain CT and enhanced MRI.CT and MRI showed that 7 cases had a round or elliptical soft tissue mass, and 4 cases with well defined margin,3 cases were not clear in edge,2 cases with spot or strip calcification on CT images,4 cases had slightly longer T1 and longer T2 signal,4 cases were restricted of diffusion and had higher signal on DWI.All the lesions were enhanced in arterial phase,and went on in the delayed phase.There were 5 cases with distorted vascular shadow in the middle and/or around of the mass, 3 cases with strips,spoke-like low-density areas or low-signal areas,and some lesions were filled in delayed phase.Conclusion CT and MRI features of hyaline vascular type LCD have certain characteristics such as rich blood supply,enhancement in persistent,tortuosity of peripheral vascular,with some short strip calcification and high signal on DWI,which may be helpful for preoperative diagnosis.

Objective: To investigate the history, risk factors for prognosis of malignant biliary stricture (MBS) patients receiving conservative therapy after endoscopic retrograde cholangiopancreatography(ERCP) and to set up a predictive model for overall survival (OS). Methods: MBS patients who underwent ERCP and conservative therapy in Xijing Hospital and PLA No.451 Hospital from January 2009 to December 2013 were enrolled to the present study. Predictive factors associated with OS were identified in the training cohort by stepwise multivariate Cox regression analysis. A predictive model was then developed and externally validated in the validation cohort. Results: Between January 2009 and December 2013, 152 and 149 patients were eligible to the training and validation cohort respectively. In the training cohort, tumors were mainly originated from bile duct (33.6%), pancreas (23.5%) or ampulla (20.4%). 76.3% (116/152) patients died during the observation period. The median OS for the training population was 5.0 months (3.9-6.2 months). CA19-9≥1 000 U/mL, non-ampulla tumor, metastasis, pre-ERCP total bilirubin≥7 mg/dL and hilar stricture were identified as independent predictive factors of poor OS (all P<0.05). Based on these factors, the COMTH predictive model was developed. The median OS of patients with COMTH>8 in the training and validation cohorts were both 3.0 months, which were significantly shorter than those with COMTH≤8 (10.0 and 6.9 months in the training and validation cohorts respectively, both P<0.001). Conclusion The prognosis of MBS patients undergoing ERCP is poor. The survival chance of patients with COMTH>8 is even more dismal.

Objective To investigate the clinical outcome of pancreatic pseudocyst(PPC)treated with non-surgical methods,and to compare the efficacy and safety between percutaneous drainage and endoscopic drainage in the management of PPC.Methods From February 2010 to July 2017,clinical data of patients with PPC,who received percutaneous drainage or endoscopic drainage,were retrospectively analyzed.The symptom relief rate,short-term and long-term radiologic remission rate,complication rate, recurrence rate and length of hospital stay were compared between patients treated by ultrasound guided percutaneous drainage(percutaneous group),by endoscopic ultrasonography-guided drainage(EUS group)and by endoscopic retrograde pancreatography guided transpapillary drainage(ERP group).Two independent samples t test,one-way analysis of variance,non-parametric test and Fisher′s exact test were performed for statistical analysis.Results A total of 153 patients were treated and the operation was successfully conducted in 148 patients(96.7%),of whom 39 were in percutaneous group,73 in EUS group and 36 in ERP group.The median follow-up time was 26 weeks(two weeks to 358 weeks).The symptom relief rate,long-term radiographic remission rate,complication rate,recurrence rate and retreatment rate of percutaneous group,EUS group and ERP group were 87.2%(34/39),79.5%(58/73),80.6%(29/36);81.5%(22/27),88.6%(39/44),66.7%(16/24);17.9%(7/39),28.8%(21/73),16.7%(6/36);15.0%(3/20),13.8%(8/58),10.0%(2/20);and 10.3%(4/39),8.2%(6/73),2.8%(1/36),respectively.There was no statistically significant difference among three groups (all P> 0.05).The short-term radiographic remission rate of ERP group was significantly lower than those of percutaneous group and EUS group(46.7%,14/30 vs 77.1%,27/35 and 87.7%,64/73),and the differences were statistically significant(χ2 =6.442 and 19.450,both P<0.01).The median hospital stay of percutaneous group was longer than those of EUS group and ERP group(14.0 days vs 9.0 days and 8.0 days),and the differences were statistically significant(Z= -3.687 and -2.630,both P<0.01).Conclusions The efficacies of percutaneous drainage and EUS-guided drainage are both better than ERP,and they are effective and safe methods especially for the patients with complication of pseudocysts and necrosis debris in pseudocysts.However,the hospitalization time of percutaneous drainage is longer. In addition,percutaneous drainage can be an alternative method after failed endoscopic drainage.

As a model organism, zebrafish have many advantages over other animal models and is suitable for studies on establishment of human disease model and mechanism.In zebrafish, there are two phases of endocrine formation during early development, which are directed by concomitant activity of many signaling pathways.Zebrafish pancreas possess similar cell structure with that of other animals, which can express various endocrine hormones including insulin.The main organs required for metabolic control, such as the pancreas, islet, and insulin sensitive tissue (muscle, liver) are conserved in zebrafish, and the mechanisms of glucose regulation in zebrafish is similar to that seen in mammalian models.These render it an excellent model to study glucose metabolism.Hyperglycemia in zebrafish model can be induced by administration of the diabetogenic drug, streptozotocin (STZ), alternatively immersion of the fish in glucose solution and water, or disturbing of signaling pathways associated with glucose metabolism.Glucose levels in adult zebrafish blood or embryo tissue and phenotype of retinal cell layers or retinal vasculature are the commonly used measurement organs in zebrafish diabetic models.

Objective To investigate the relationship between hereditary deafness and SLC26A4 gene IVS16+10C>T mutation.Methods One hundred and two patients with hereditary deafness admitted to the Third Affiliated Hospital of Qiqihar Medical College from January 2014 to May 2016 were enrolled and assigned as the observation group, and another 102 cases with normal hearing were selected as the control group. The gene mutation types and hearing thresholds were detected in the two groups and compared between them, the mutations of alleles 1 and 2 situations of patients with GJB2 and SLC26A4 mutations were analyzed, Ab initio software was used to predict whether there was obstacle preventing the recognition on slice sites, and polymerase chain reaction (PCR) was adopted to detect the common mutation types of SLC26A4 gene.Results In 102 patients with hereditary deafness, the cases caused by SLC26A4 gene mutations were more than those caused by GJB2 gene mutations (30 cases vs. 15 cases). Compared with the normal hearing control group, the mutation rates of GJB2 and SLC26A4 genes were significantly increased in the observation group [GJB2: 14.71% (15/102) vs. 2.94% (3/102), SLC26A4: 29.41% (30/102) vs. 1.96%(2/102), bothP <0.01], and there was a tendency that the percentages of GJB2 and SLC26A4 mutations were increased (GJB2: 0.98%, 1.96%, 4.90%, 6.86%, SLC26A4: 4.90%, 6.86%, 7.84%, 9.80%) with the increase of the severity of deafness (mild—moderate—severe—extreme severe) in the observation group. Compared with the control group, the hearing threshold was significantly increased (dB: 67.83±8.96 vs. 10.43±2.89,P < 0.01), and along with the increase of deafness severity (mild—moderate—severe—extreme severe), the hearing threshold (dB) was increased (34.96±4.98, 58.42±10.61, 83.96±12.17, 96.77±11.42, respectively) in the observation group. Thirty patients with SLC26A4 gene did not show any IVS16+10C>T mutation, indicating that IVS16+10C>T gene mutation was not the cause of genetic deafness.Conclusion There is no obvious relationship between the IVS16+10C>T mutation of SLC26A4 gene and patients with hereditary deafness, which may provide a basis clinically for the prediction of deafness occurrence in the patient's next generation.

Objective To analyze the risk factors of post-ERCP pancreatitis (PEP) and to evaluate the relationship between cannulation time and PEP.Methods The data of cannulation time in 1 625 patients who underwent ERCP from 2010 to 2012 were retrospectively studied.The risk factors associated with PEP were analyzed by univariate and multivariate Logistic regression analysis.The effect of different cannulation time on PEP was evaluated.Results The incidence of overall PEP was 4.6％ (75/1 625) including 4.1％ (67/1 625)of mild and 0.5％ (8/1 625)of moderate-to-severe.Univariate analysis revealed that diabetes mellitus (P =0.02),choledocholithiasis (P =0.02),malignant biliary stenosis (P =0.007),duodenal stenosis (P =0.029),precut (P＜0.01),cannulation time ≥ 8 min (P＜0.01),blood platelet count ≥ 180× 109/L(P =0.089),alkaline phosphatase ≥ 120 U/L (P =0.083) and total bilirubin ≥ 17.1 μmol/L (P =0.094)were associated with PEP.Multivariate analysis revealed that precut (OR=1.93,95％CI:1.10-3.39,P=0.022),cannulation time ≥8 min (OR =3.50,95％CI:2.00-6.13,P＜0.01) and duodenum stenosis (OR=2.92,95％CI:1.08-7.86,P=0.034) were independent risk factors of PEP.Within 30 min of cannulation,longer cannulation time was accompanied with higher PEP rate.Conclusion The cannulation time is an independent risk factor of PEP.Overall PEP is increased when cannulation time is more than 8 min.