Objective To investigate the new-onset conduction block after transcatheter aortic valve replacement (TAVR) and summarize the relevant experience. Methods The perioperative data of TAVR patients in the Second Hospital of Hebei Medical University from January 2016 to February 2023 were collected, and the new-onset incidence of conduction block after TAVR was analyzed retrospectively. Results Finally 352 patients were included, including 225 males and 127 females, with an average age of (67.2±5.1) years, among whom 256 patients were treated with Venus-A valves, 69 patients with Vita-Flow valves, and 27 patients with J-Valve valves. There were 38 (10.8%) patients of new-onset postoperative block. There were 6 (1.7%) patients of new-onset postoperative grade Ⅲ atrioventricular block, including 5 (2.0%) patients of Venus-A and 1 (1.4%) patient of Vita-Flow. Conduction function was restored in 2 patients within 14 days after surgery, and failed to be restored in 4 patients, who then received permanent pacemaker implantation in the Department of Cardiology. There were 27 (7.7%) patients of new left bundle branch block after surgery, including 22 (8.6%) patients of Venus-A, 4 (5.8%) patients of Vita-Flow and 1 (3.7%) patient of J-Valve; and conduction function was restored within 7 days after surgery in 23 patients, and 5 (1.4%) patients developed new right bundle branch blocks after surgery including 4 (1.5%) patients of Venus-A and 1 (1.4%) patient of Vita-Flow. Conclusion New-onset conduction block is a common complication after TAVR, and the new-onset rate of left bundle branch block is the highest, followed by the grade Ⅲ atrioventricular block. Mastering reasonable methods and applying appropriate strategies can effectively reduce the new-onset rate of postoperative conduction block and improve the overall success rate of TAVR surgery.

Objective To analyze the short-term clinical outcomes of emergency conversion to surgery during transcatheter aortic valve replacement (TAVR). Methods Clinical data of patients who underwent emergency surgical conversion from TAVR in the Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University, from 2018 to 2023 were collected. Postoperative follow-up results at 1 month were recorded. Results A total of 253 patients underwent TAVR, of whom 11 (4.3%) required emergency conversion to surgery. Among these 11 patients, 7 were male and 4 were female, with a mean age of (69.55±5.01) years. The primary cause for emergency surgical conversion was valve stent displacement (63.6%), followed by left ventricular perforation/rupture (18.2%) and significant perivalvular regurgitation persisting after a second valve implantation (18.2%). One (9.1%) patient died intraoperatively. Among the 10 surviving patients, postoperative complications included pulmonary infection in 8 patients, severe pneumonia in 7, pleural effusion in 3, liver dysfunction in 8, renal dysfunction in 3, upper gastrointestinal bleeding in 5, cerebrovascular complications in 1, atrial fibrillation in 1, ventricular premature contractions in 1, atrioventricular block in 1, and complete left bundle branch block in 3. At 1-month postoperative follow-up, one additional patient died, yielding a 30-day mortality rate of 18.2% after TAVR emergency surgical conversion. The quality of life improved significantly compared to preoperative status in 9 (81.8%) patients, and no patients were readmitted for cardiovascular diseases. Conclusion The incidence of emergency conversion to surgery during TAVR is low, but the rates of surgical complications and 30-day postoperative mortality are high. Nevertheless, when severe complications occur during TAVR, emergency conversion to surgery can still yield satisfactory short-term clinical outcomes for a majority of these patients.

ObjectiveTo evaluate some properties of scutellarin-phospholipid complex nanoemulsion（SCU-PC-NE）， such as release， cell uptake and tissue distribution， and to investigate its effect on ameliorating lipopolysaccharide（LPS）-induced vascular endothelial injury. MethodSCU-PC-NE was prepared by weighting SCU-PC， ethyl oleate， Kolliphor HS15， 1，2-propylene glycol（50， 400， 514.3， 85.7 mg）， respectively. And the appearance of SCU-PC-NE was observed by transmission electron microscope， the average paticle size and Zeta potential were measured by nanopotential particle size analyzer. The cumulative release of SCU-PC-NE in vitro was measured by dynamic dialysis， thiazolyl blue（MTT） colorimetric assay was used to investigate the effect of SCU-PC-NE on the viability of human umbilical vein endothelial cells（HUVECs）， the inverted fluorescence microscope and flow cytometry were used to investigate cell uptake of HUVECs by SCU-PC-NE in vitro using coumarin 6 as a fluorescent probe， the tissue distribution of DiR/SCU-PC-NE labeled by near infrared fluorescent dyes was obeserved by small animal in vivo imaging system. The inflammation injury model was established by co-incubation with LPS（1 mg·L^-1） and HUVECs， the effect of SCU-PC-NE on the levels of interleukin（IL）-1β and IL-6 were determined by enzyme-linked immunosorbent assay（ELISA）， 18 Kunming male mice were randomly divided into blank group， model group， blank preparation group（equivalent to high dose group）， SCU group and SCU-PC-NE low and high dose groups（5， 10 mg·kg^-1）， 3 mice in each group， and the drug administration groups were administered once in the tail vein at the corresponding dose every 48 h， equal volume of normal saline was given to the blank group and the model group， and the drug was administered for 4 consecutive times. Except for the blank group， the endothelial inflammatory injury was induced by intraperitoneal injection of LPS（10 mg·kg^-1） at 12 h before the last administration in each group. Hematoxylin-eosin（HE） staining was used to investigate the effect of SCU-PC-NE on the histopathological changes in the thoracic aorta of mice. ResultThe appearance of SCU-PC-NE displayed pale yellow milky light， mostly spherical with rounded appearance and relatively uniform particle size distribution， with the average particle size of 35.31 nm， Zeta potential of 7.23 mV， and the encapsulation efficiency of 75.24%. The cumulative release in vitro showed that SCU-PC-NE exhibited sustained release properties compared with SCU. The cell viability of SCU-PC-NE was >90% at a concentration range of 1.05-8.4 mg·L^-1. The results of cellular uptake experiments showed that the cellular uptake ability of SCU-PC-NE was significantly enhanced when compared with the SCU group（P<0.01）. Compared with normal mice， the results of tissue distribution showed that the fluorescence intensity of DiR/SCU-PC-NE was significantly enhanced in the spleen， kidney， brain and thoracic aorta of mice at different time points after intraperitoneal injection of LPS（P<0.05， P<0.01）， especially in thoracic aorta. ELISA results showed that the levels of IL-1β and IL-6 in the model group were significantly increased when compared with the blank group（P<0.05， P<0.01）， and compare with the model group， all administration groups significantly down-regulated IL-1β level， with the strongest effect in the SCU-PC-NE high-dose group（P<0.01）， and all administration groups significantly down-regulated IL-6 level， with the strongest effect in the SCU-PC-NE low-dose group（P<0.05）. Compare with the blank group， the results of HE staining showed that the endothelial cells were damaged， the elastic fibers were broken and arranged loosely in the model group， although similar vascular injury could be observed in the blank preparation group， SCU group and SCU-PC-NE low-dose group， the vascular endothelial damage was significantly reduced in the high-dose group of SCU-PC-NE， which had a better effect than that in the SCU group. ConclusionSCU-PC-NE can promote the uptake of drugs by endothelial cells and effectively enriched in the site of vascular endothelial injury caused by LPS， suggesting that it has a protective effect on vascular endothelial injury and is a good carrier of SCU.

Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.

Objective To analyze the short-term clinical efficacy and prognosis of one-stop transcatheter aortic valve replacement (TAVR)+percutaneous coronary intervention (PCI) in the treatment of aortic valve disease with coronary heart disease. Methods The clinical data of patients with aortic valve disease complicated with coronary heart disease who underwent one-stop TAVR+PCI treatment at the Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University from January 2018 to June 2023 were retrospective analyzed. The preoperative and postoperative clinical data were compared, and 1-month follow-up results were recorded. Results A total of 37 patients were enrolled, including 22 males and 15 females, with an average age of 69.14±6.47 years. Thirty-six patients recovered and were discharged after the surgery, and 1 (2.7%) patient died during the surgery. Self-expanding TAVR valves were implanted through the femoral artery in all patients. One coronary artery was opened by PCI in 35 (94.6%) patients, and two coronary arteries were opened by PCI in 2 (5.4%) patients. All PCI opened arteries had a stenosis>70%. During the postoperative hospitalization, the complications included pulmonary infection in 11 (30.6%) patients, severe pneumonia in 10 (27.8%) patients, liver function injury in 14 (38.9%) patients, renal function injury in 5 (13.9%) patients, cerebral infarction in 1 (2.8%) patient, atrial fibrillation in 1 (2.8%) patient, ventricular premature beats in 2 (5.6%) patients, atrioventricular block in 2 (5.6%) patients, and complete left bundle branch block in 5 (13.9%) patients. The median postoperative ventilation assistance time was 12.0 (0.0, 17.0) h, the ICU monitoring time was 1.0 (0.0, 2.0) d, and the postoperative hospitalization time was 5.0 (4.0, 7.0) d. There was a significant improvement in the New York Heart Association cardiac function grading after surgery (P<0.001). After surgery, there were 21 (58.3%) patients had minor perivalve leakage, 6 (16.7%) patients had minor to moderate perivalve leakage, and no moderate or above degree of perivalve leakage. After one month of postoperative follow-up, 36 patients showed significant improvement in heart function. There were no patients with recurrent acute coronary syndrome, re-PCI, or cardiovascular system disease related re-hospitalization. Conclusion The one-stop TAVR+PCI treatment for patients with aortic valve disease and coronary heart disease can obtain satisfactory short-term clinical efficacy, which is worth further trying and studying.

Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.
China ; Cystic Fibrosis/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Humans ; Mutation ; Poly T ; RNA, Messenger/genetics*

The RET(REarranged during transfection) gene as a novel has broken the therapeutic deadlock in the last two years, whith is attributed to the rapid approval of targeted therapies and inclusion in treatment guidelines, bringing more hope for the survival of patients with non-small cell lung cancer(NSCLC). Usually, the main activation of the RET proto-oncogene contributes to the development of lung cancer via somatic rearrangements. Thus, this study reviews the biological characteristics of RET gene, the classification of RET fusion in lung cancer and the detection of RET fusion. Meanwhile the pathological and clinical features, targeted therapies, drug resistance, prognosis of lung cancer patients with RET fusion were further discussed.

OBJECTIVE: To analyze the clinical phenotype and MYH7 gene variant in a Chinese pedigree affected with hypertrophic cardiomyopathy (HCM). METHODS: The proband was screened for variant of 96 cardiomyopathy-associated genes by exonic amplification and high-throughput sequencing. Candidate variant was verified by Sanger sequencing among 300 healthy controls as well as family members of the proband. Co-segregation analysis of genotypes and clinical phenotypes was carried out for the pedigree. Clustal X software was used to analyze the sequence conservation of the variant among various species, and its pathogenicity was predicted by using bioinformatics software. RESULTS: 6 out of 12 members from this pedigree were found to harbor heterozygous c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene, among whom five were diagnosed with HCM. The remaining one had failed to meet the diagnostic criteria for HCM, but had abnormal ECG. The same variant was not found in the 300 healthy controls. Amino acid sequence analysis showed that the variant is located in a highly conserved region, and bioinformatics analysis predicted that this variant may affect protein function and has a deleterious effect. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM2+ PP1_Moderate+PP3+PP5). CONCLUSION The c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene probably underlay the pathogenesis in this pedigree. Above finding has important value for the early diagnosis of patients with HCM.
Cardiac Myosins/genetics* ; Cardiomyopathy, Hypertrophic/genetics* ; Genotype ; Humans ; Mutation ; Myosin Heavy Chains/genetics* ; Pedigree ; Phenotype

Objective:To evaluate the 2-dimension and 3-dimension changes of upper airway of patients who were diagnosed with idiopathic condylar resorption (ICR) and anterior open bite as well as received bilateral temporomandibular joint (TMJ) prostheses replacement or bimaxillary orthognathic surgery.Methods:This study is a retrospective study. Seventeen patients diagnosed as ICR and anterior open bite in Department of Orthognathic and TMJ surgery, West China Hospital of Sichuan University were selected (January 2018 to December 2021) and divided into bilateral TMJ protheses replacement group (group R, n=8) and orthognathic group (group O, n=9), according to which surgery they have performed. In order to compare variation of upper airway before and after surgery in different dimensions and sections within the same group or between groups, Spiral computed tomography data were obtained before (1 month) and after operation (10 to 12 months) to measure the total volume of airway (VT), the maximum sagittal area (MSA), the maximum cross-sectional area (MACA), the minimum cross-sectional area (MICA), the area of the most posterior plane(PPA), the area of soft-palate plane (SPA), the area of the most posterior point of tongue base plane (PTA), the area of the root of epiglottis plane (EA), the oropharyngeal airway volume (VO), the glossopharyngeal airway volume (VG) and the laryngeal airway volume (VL). Wilcoxon signed-rank test were used to complete statistical analyses for VO (T2),SPA (T2),ΔMSA,ΔMACA in group R as well as PTA (T1),EA (T2) in group O. Statistical analyses of other items were performed with student′s t test. Results:VT, VO, VG, VL, MSA, MACA, MIC, PPA, PTA and EA of group R (T2) were significantly increased after TMJ prosthesis with Lefort Ⅰ osteotomy ( P<0.05). Meanwhile the VT, VO, VG, MSA, MACA, MICA, PPA and SPA of group O (T2) were significantly increased ( P<0.05). There were significant difference in ΔVT and ΔVL between group R [(6 854.80±3 197.82) mm 3, (2 252.85±1 527.96) mm 3] and group O [(3 367.91±3 124.62) mm 3, (413.21±1 244.44) mm 3]( t=2.27, P=0.038; t=2.74, P=0.015). Conclusions:Bilateral temporomandibular joint (TMJ) prostheses replacement and bimaxillary orthognathic surgery can both enlarge the areas and volumes of upper airway in patients who suffer from ICR and anterior open bite. Compared with bimaxillary orthognathic surgery, bilateral temporomandibular joint prostheses replacement plays a more pronounced role in enlargement and reconstruction of middle-inferior section of upper airway.

Due to the impact of COVID-19, the online problem-based learning (PBL) teaching mode was first implemented based on the curriculum integration of basic medicine and clinical medicine in our university in 2020. A total of 357 eight-year program clinical medicine students from three grades participated in the online PBL courses. The students have had related skills and knowledge of integration curriculum, and the teachers have carried out sufficient analysis of learning situation, preparation of software and hardware, as well as teaching design. Teachers and students has communicated with each other smoothly and cooperated closely through the Tencent Conference software platform, therefore this teaching mode has gained better feedback among students, with higher satisfaction of courses and significantly improved students' learning enthusiasm. The curriculum integration has laid the foundation for the case design and application of online PBL teaching, while the success of online PBL teaching has also reflected the original intention of curriculum integration reform.