Objective To investigate the correlation between novel bone metabolism markers and the degree of aortic calcification as well as cardiovascular event risk in elderly patients treated by PD.Methods A prospective trial was conducted on 230 elderly patients receiving continuous am-bulatory PD in our department from February 2022 to February 2024.According to the occur-rence of cardiovascular events during dialysis treatment,they were divided into a cardiovascular event group(n=92)and a control group(n=138).Relevant clinical data were collected,aortic calcification was assessed using AAC scores,and serum levels of bone metabolism markers,inclu-ding osteoprotegerin,TRACP,and PINP were measured.Results The serum levels of osteoprote-gerin,TRACP and PINP were significantly higher in the cardiovascular event group than the con-trol group(P＜0.01).The cardiovascular event group had obviously severe calcification and higher AAC score than the control group(P＜0.01).The serum levels of the three bone metabolism markers were notably higher in the patients with severe calcification than those with moderate calcification,followed by mild calcification in turn(P＜0.01).Spearman correlation analysis indi-cated that the levels of the three indicators were positively correlated with the degree of aortic cal-cification in elderly PD patients(r=0.465,P=0.000;r=0.396,P=0.000;r=0.434,P=0.000).Multivariate logistic regression analysis showed that these three indicators were risk factors for cardiovascular events in elderly PD patients(P＜0.01).Conclusion The three bone metabolism markers are significantly correlated with aortic calcification severity and cardiovascular event risk in elderly PD patients.Monitoring these marker levels may be helpful for the assessment and man-agement of cardiovascular risk.

Objective To investigate the correlation between novel bone metabolism markers and the degree of aortic calcification as well as cardiovascular event risk in elderly patients treated by PD.Methods A prospective trial was conducted on 230 elderly patients receiving continuous am-bulatory PD in our department from February 2022 to February 2024.According to the occur-rence of cardiovascular events during dialysis treatment,they were divided into a cardiovascular event group(n=92)and a control group(n=138).Relevant clinical data were collected,aortic calcification was assessed using AAC scores,and serum levels of bone metabolism markers,inclu-ding osteoprotegerin,TRACP,and PINP were measured.Results The serum levels of osteoprote-gerin,TRACP and PINP were significantly higher in the cardiovascular event group than the con-trol group(P＜0.01).The cardiovascular event group had obviously severe calcification and higher AAC score than the control group(P＜0.01).The serum levels of the three bone metabolism markers were notably higher in the patients with severe calcification than those with moderate calcification,followed by mild calcification in turn(P＜0.01).Spearman correlation analysis indi-cated that the levels of the three indicators were positively correlated with the degree of aortic cal-cification in elderly PD patients(r=0.465,P=0.000;r=0.396,P=0.000;r=0.434,P=0.000).Multivariate logistic regression analysis showed that these three indicators were risk factors for cardiovascular events in elderly PD patients(P＜0.01).Conclusion The three bone metabolism markers are significantly correlated with aortic calcification severity and cardiovascular event risk in elderly PD patients.Monitoring these marker levels may be helpful for the assessment and man-agement of cardiovascular risk.

Objective:To compare the antiplatelet effects of vicagrel and clopidogrel in patients with different cytochrome P450 (CYP) 2C19 genotypes.Methods:This is a post-hoc analysis of a phase Ⅱ clinical trial of vicagrel, which included patients with coronary heart disease who underwent percutaneous coronary intervention from August 2018 to June 2019 in 18 centers. Patients were categorized based on the presence of CYP 2C19 *2 or *3 loss-of-function (LOF) alleles into LOF carrier group ( n=111) and non-LOF carrier group ( n=90). Each group included patients received vicagrel 5 mg, 6 mg, 7.5 mg, or clopidogrel 75 mg for 28 days per study protocol. P2Y 12 reaction units (PRU) were measured using VerifyNow at baseline, 6 to 8 hours after loading dose, 7 to 10 days after randomization, and 28 days after randomization and the percentage inhibition of platelet aggregation (%IPA) was calculated. The primary endpoint was %IPA on day 28. Within the patients from the General Hospital of Northern Theater Command, 8 to 12 patients in each study arms were enrolled in a prespecified pharmacokinetic sub-study, measuring the time to reach maximum plasma concentration (T max), peak plasma concentration (C max), and area under the plasma concentration-time curve (AUC). Results:Among 201 patients, the age was (58.8±8.5) years, and 139 (69.2%) were male. In non-LOF carriers, there was no significant differences in PRU values and %IPA between the vicagrel 5 mg, 6 mg, 7 mg, and clopidogrel groups at all time points (all P>0.05). In LOF carriers, %IPA was significantly higher in the vicagrel-treated groups than in the clopidogrel group at 6-8 hours after loading dose (22.9 (14.2, 31.5)% vs. 19.8 (11.0, 28.6)% vs. 29.5 (20.9, 38.0)% vs. 12.9 (3.9, 21.9)%, P=0.038) and 7-10 days after randomization (22.4 (14.2, 30.5)% vs. 34.4 (26.1, 42.6)% vs. 39.8 (31.8, 47.9)% vs. 24.7 (16.3, 33.2)%, P=0.001), with a trend towards higher %IPA in the vicagrel-treated groups at day 28 (30.4 (21.3, 39.6)% vs. 36.5 (27.2, 45.7)% vs. 40.8 (31.8, 49.8)% vs. 30.7(21.2, 40.2)%, P=0.056). Pharmacokinetic results of 35 patients showed that the C max and AUC of the active metabolite M15-2 of vicagrel was similar to that of clopidogrel in non-LOF carriers, but AUC between vicagrel 5 mg, 6 mg, 7 mg and clopidogrel were significantly different in LOF carriers ((5.6±0.6) h·μg -1·L -1 vs. (6.8±2.7) h·μg -1·L -1 vs. (9.2±3.3) h·μg -1·L -1 vs. (4.2±1.9) h·μg -1·ml -1, P=0.020). Conclusion:Vicagrel and clopidogrel have similar antiplatelet effects in non-LOF carriers, but vicagrel exhibits superior antiplatelet effects in LOF carriers.

OBJECTIVE: To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure. METHODS: Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations. CONCLUSION Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.
Abnormalities, Multiple/genetics* ; Bone Diseases, Developmental/genetics* ; Epilepsy/genetics* ; Facies ; Humans ; Intellectual Disability/genetics* ; Phenotype ; Repressor Proteins/genetics* ; Seizures/genetics* ; Tooth Abnormalities/genetics*

OBJECTIVE: To explore the genetic bases of 3 patients with periventricular nodular heterotopia and epileptic seizure. METHODS: The clinical data of three patients presenting with periventricular nodular ectopic with epileptic seizure were analyzed. Whole exome sequencing (WES) was performed on the patients, and Sanger sequencing was used to validate the suspected variants. RESULTS: In three female patients, head MRI showed nodular gray matter ectopic in the bilateral ventricle. WES identified the heterozygous c.2720del T(p.Leu907Argfs*39) variant of FLNA gene in case 1 and her mother (case 2), and heterozygous c.1387_1390del GTGC(p.Val463Profs*34) of FLNA gene in case 3. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC (p.Val463Profs*34) variants of FLNA gene were predicted to be pathogenic (PVS1+PM2+PP1) and likely pathogenic(PVS1+PM2), respectively. CONCLUSION The c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC(p.Val463Profs*34) variants of FLNA gene may be the genetic cause of the three patients.
Epilepsy/genetics* ; Female ; Filamins/genetics* ; Heterozygote ; Humans ; Magnetic Resonance Imaging ; Mutation ; Periventricular Nodular Heterotopia/genetics* ; Seizures

Objective    To evaluate the clinical value of three-dimensional (3D) printing model in accurate and minimally invasive treatment of double outlet right ventricle (DORV). Methods    From August 2018 to August 2019, 35 patients (22 males and 13 females) with DORV aged from 5 months to 17 years were included in the study. Their mean weight was 21.35±8.48 kg. Ten patients who received operations guided by 3D printing model were allocated to a 3D printing model group, and the other 25 patients who received operations without guidance by 3D printing model were allocated to a non-3D printing model group. Preoperative transthoracic echocardiography and CT angiography were performed to observe the location and diameter of ventricular septal defect (VSD), and to confirm the relationship between VSD and double arteries. Results    The McGoon index of patients in the 3D printing model group was 1.91±0.70. There was no statistical difference in the size of VSD (13.20±4.57 mm vs. 13.40±5.04 mm, t=−0.612, P=0.555), diameter of the ascending aorta (17.10±2.92 mm vs. 16.90±3.51 mm, t=0.514, P=0.619) or diameter of pulmonary trunk (12.50± 5.23 mm vs. 12.90±4.63 mm, t=−1.246, P=0.244) between CT and 3D printing model measurements. The Pearson correlation coefficients were 0.982, 0.943 and 0.975, respectively. The operation time, endotracheal intubation time, ICU stay time and hospital stay time in the 3D printing model group were all shorter than those in the non-3D printing model group (P<0.05). Conclusion    The relationship between VSD and aorta and pulmonary artery can be observed from a 3D perspective by 3D printing technology, which can guide the preoperative surgical plans, assist physicians to make reasonable and effective decisions, shorten intraoperative exploration time and operation time, and decrease the surgery-related risks.

It has been observed that both cancer tissue cells and normal proliferating cells (NPCs) have the Warburg effect. Our goal here is to demonstrate that they do this for different reasons. To accomplish this, we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer types in TCGA and data of five NPC types in GEO. Our analyses reveal that NPCs accumulate large quantities of ATPs produced by the respiration process before starting the Warburg effect, to raise the intracellular pH from ∼6.8 to ∼7.2 and to prepare for cell division energetically. Once cell cycle starts, the cells start to rely on glycolysis for ATP generation followed by ATP hydrolysis and lactic acid release, to maintain the elevated intracellular pH as needed by cell division since together the three processes are pH neutral. The cells go back to the normal respiration-based ATP production once the cell division phase ends. In comparison, cancer cells have reached their intracellular pH at ∼7.4 from top down as multiple acid-loading transporters are up-regulated and most acid-extruding ones except for lactic acid exporters are repressed. Cancer cells use continuous glycolysis for ATP production as way to acidify the intracellular space since the lactic acid secretion is decoupled from glycolysis-based ATP generation and is pH balanced by increased expressions of acid-loading transporters. Co-expression analyses suggest that lactic acid secretion is regulated by external, non-pH related signals. Overall, our data strongly suggest that the two cell types have the Warburg effect for very different reasons.

Objective The aim of this study was to investigate the dosimetric advantages of Gating in the treatment of prima-ry hepatic cancer with large segmentation. Methods A retrospective analysis of 10 patients with primary liver cancer from August 2017 to November 2018 after interventional therapy was performed using three consecutive phases of end-tidal phase to achieve pa-tient-controlled large-segment radiotherapy. Ten patients underwent 4DCT localization scan,and 10 respiratory phase sequences were reconstructed by respiratory wave-form,and the images were transmitted to the MIM6. 7. 6 workstation. In the MIM workstation, full-time phase maximum density projection(MIP-10),full-time phase average density projection(Mean-10),end-expiration 3 phase maximum density projection(MIP-3) and end-expiration 3 phase average density projection( Mean-3) were generated re-spectively,where MIP was used for target delineation and Mean for dose calculation. The radiotherapy doctor delineated IGTV-10 and IGTV-3 on the MIM workstation,and released CTV-10,CTV-3,PTV-10 and PTV-3 to compare the volume differences of the target area. After the target area was drawn,the image was transmitted from the MIM workstation to the Eclipse treatment planning sys-tem,and the full-time phase plan(Plan-10)with the same conditions and three consecutive phase-phase gating plans(Plan-3) were prepared. The prescriptive dosage was given at 50 Gy/10 f/2weeks. Comparing the HI and CI of the target area,the comparison of organs at risk included: the average dose of liver Dmean,the irradiation volume of liver less than 15Gy,the Dmax of small intestine, the Dmax of colon, the Dmax of stomach, the average dose of the kidney Dmean, the heart Dmax, and the spinal cord Dmax. Results The volume of the target area delineated at the end of expiratory phase was less than that of the target area outlined by the full-time phase in IGTV,CTV and PTV,and the difference was statistically significant(P<0. 05). In the two groups of seven field coplanar lage-segment radiotherapy plans,the 3-phase respiratory gating plan significantly reduced the dose of the organs at risk, and the difference was statistically significant(P<0. 05). At the same time,there was no statistically difference in the HI and CI be-tween of the two groups(P>0. 05). Conclusion The gated target area delineation and planning design of the three consecutive pha-ses of end-tidal phase reduce the volume of IGTV,CTV and PTV target regions compared with the selection of full-time phase,and have obvious advantages in the planned dosimetry. The irradiation dose that threatens the organs is worthy of being promoted and ap-plied in the large-scale radiotherapy of liver cancer.

Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.
Biomedical Research ; methods ; trends ; Clinical Trials as Topic ; Genetic Predisposition to Disease ; genetics ; Genetic Therapy ; methods ; trends ; Humans ; Mutation ; Retinal Diseases ; genetics ; therapy ; Treatment Outcome

To investigate and step in the compliance of clinician hand hygiene, we used vari-ous management tools of the quality control circle (QCC), and then compared the change of the com-pliance before and after any operations. Firstly, we followed this 5 steps: selecting themes, drafting plans, grasping current situations, setting goals and analyzing objectives. Then, we formulated and im-plemented the interventions pertinently. All of the QCC members participated actively in the whole process. The compliance of clinician hand hygiene was improved from 41.11%to 57.59%. The realiza-tion rate was 115.97%, the progress rate was 40.99%, and the hand hygiene compliance of hand hy-giene in different time was significantly improved with the average value 1.25. Standardized result formed by quality control circle activity had a comprehensive promotion in the hospital and promoted the management of hospital infection and the development of hospital.