Bibliometric and visual analysis of Chinese scarlet fever literature / 公共卫生与预防医学

Objective To analyze the research status and trend of scarlet fever literature in China, and to provide reference for subsequent research. Methods Three major Chinese databases, CNKI, Wanfang, and VIP, as well as Web of Science English database, were used to search for literature related to scarlet fever from 2000 to 2023. Citespace6.2.R2 software was used to statistically analyze the number of publications, authors, institutions and journals, co-cited literature, keyword clustering, and other literature characteristics of the literature. Results From 2000 to 2023, a total of 1 011 Chinese literature were included in the three major Chinese databases. Since 2011, the number of publications had gradually increased, but in recent years, the number of publications had decreased. The organization with the most publications was the Shenyang Center for Disease Control and Prevention. The cluster analysis of key words mainly formed 9 cluster tags, and the high-frequency keywords mainly included epidemic characteristics, epidemiology, incidence rate, etc. A total of 84 English literature were included in the WOS database, with an overall upward trend in publication volume. The institution with the most publications was the China Center for Disease Control and Prevention, and the most frequently cited journal was “LANCET INFECT DIS”.《Resurgence of scarlet fever in China: a 13-year population-based surveillance study》 was the most cited journal. After keyword cluster analysis, 9 cluster labels were mainly formed, and the keywords were mainly outbreak，Hong Kong, and Group A streptococcus. Conclusion Compared with the English literature, which mainly focuses on spatiotemporal aggregation, etiology and strain resistance, Chinese literature focuses more on epidemic surveillance, clinical features and quality nursing.

Retinal microstructure and developmental characteristics in Zebrafish / 解剖学报

Objective To study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.

Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injury-induced pathological vascular remodeling / 中国天然药物

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.

Research hotspots and trends of tigecycline drug resistance: A study based on CiteSpace / 公共卫生与预防医学

Objective To explore the research progress, research hotspot and development trend of tigecycline resistance based on the quantitative analysis and visualization function of CiteSpace. Methods The data were collected from 4,263 Chinese and English articles on tigecycline resistance in CNKI, Wanfang, VIP and Web of Science (WOS) databases from 2012 to 2022. CiteSpace 5.8.R3 software was used to analyze the cooperative network of authors, the cooperative network of countries and institutions, the total citation times of journals, and keywords included in the literature, to reveal the hotspots and trends of tigecycline resistance research. Results The number of articles published in English literature was higher than that in Chinese literature. China had the largest number of published documents, showing a significant international academic influence in this research field. Countries all over the world were concerned about the resistance of tigecycline, but Chinese literatures focused more on the clinical infection and prevention of tigecycline resistance, while English literatures placed special emphasis on the research about the drug resistance mechanism of tigecycline. Conclusion The research direction at home and abroad is basically the same, but the research focus has gradually shifted from the clinical treatment and monitoring of tigecycline to the molecular level of drug resistance mechanism.

Research progress of thyroid hormone in pulmonary fibrosis / 中华劳动卫生职业病杂志

Pulmonary fibrosis is end-stage of variety of heterogeneous interstitial lung disease, characterizedby excessive proliferation of fibroblasts and extracellular matrix deposition and destruction of lung parenchyma. Thyroid and lung are derived from the same endodermal cells, thyroid hormone affect the occurrence、development and prognosis of the chronic obstructive pulmonary disease, lung cancer and other lung diseases, This article reviews the role and mechanism of thyroid hormone in pulmonary fibrosis in order to provide new idea for the study of the role and mechanism of thyroid hormone in silicosis.

Analysis of drug use in medical institutions of Guangdong area during 2017-2022 / 中国药房

OBJECTIVE To analyze the situation of drug use in medical institutions of Guangdong area from 2017 to 2022， and to provide reference for the production， sale and procurement of drugs by government departments， medical insurance departments， pharmaceutical enterprises， drug sales enterprises and hospitals. METHODS Using the retrospective analysis method， based on original data from Guangdong hospital information network from 2017 to 2022， statistical analysis was conducted on the drug procurement amount of 118 medical institutions that had been online for the past 6 years， as well as the distribution of 14 major categories of drugs among all purchased drugs by online medical institutions， and sales amount of drug production enterprises. RESULTS The drug procurement amount of 118 medical institutions that had been online in Guangdong area from 2017 to 2022 showed a growth-negative growth-slow growth trend. Among the 14 major categories of drugs， the top 5 drugs in the list of consumption sum were anti-infective drugs， cardiovascular drugs， nervous system drugs， anti-tumor drugs， and digestive system drugs； among the top 200 drugs in terms of procurement amount， three major categories of drugs， namely the anti-infective drugs， anti-tumor drugs and cardiovascular system drugs， occupied the main position. The top 10 drugs in the list of procurement amounts were mainly anti-tumor drugs and cardiovascular system drugs； foreign manufacturers occupied the top 3 places in the list of sales amounts in medical institutions of Guangdong area. CONCLUSIONS In Guangdong area， the growth of drug procurement amount in medical institutions is gradually slowing down， the usage of anti-infective drugs is still abundant， the prevention and treatment of chronic diseases need great attention， and foreign pharmaceutical companies are in a leading position in the sales amount of medical institutions.

Risk factors of hepatocellular carcinoma to TACE refractoriness / 中华肝胆外科杂志

Objective:To study the risk factors of patients with hepatocellular carcinoma (HCC) to transcatheter arterial chemoembolization(TACE) refractoriness.Methods:The clinical data of 106 HCC patients who underwent TACE at the Affiliated Hospital of Xuzhou Medical University from January 2020 to December 2021 were retrospectively studied. There were 90 males and 16 females, with the age of (59.9±9.3) years. These patients were divided into the TACE-refractory group ( n=47) and the control group ( n=59) based on whether TACE refratoriness occurred after surgery. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVIKA-II), maximum diameter of tumor, number of tumor and tumor vascularization patterns between the two groups were compared. Multivariate logistic regression analysis was performed to analyse the risk factors of TACE refractoriness in patients with HCC after TACE. Results:The proportion of patients with AFP >400 μg/L, PIVIKA-II >40 AU/L, number of tumor and tumor vascularization patterns Ⅲ+ Ⅳ (uneven enhancement) were significantly higher in the TACE-refractory group than the control group (all P<0.05). The maximum diameter of tumor for patients in the TACE-refractory group was significantly larger than that in the control group ( Z=-2.41, P=0.016). Multivariate logistic regression analysis showed that patients with serum AFP >400 μg/L( OR=2.707, 95% CI: 1.008-7.271), multiple tumors ( OR=6.069, 95% CI: 2.115-17.415) and tumor vascularization patterns Ⅲ+ Ⅳ (uneven enhancement)( OR=7.813, 95% CI: 2.246-27.176) before the first TACE were at increased risks of TACE refractoriness (all P<0.05). Conclusion:Preoperative AFP >400 μg/L, multiple tumors and tumor vascularization patterns Ⅲ+ Ⅳ were independent risk factors for TACE refractoriness in patients with HCC.

Treatment strategy for pediatric supracondylar humeral fractures with callus formation and displacement neglected for over 1 week / 中华创伤骨科杂志

Objective:To investigate the treatment strategy for pediatric humeral supracondylar fractures with callus formation and displacement neglected for over 1 week.Methods:A retrospective analysis was made of the clinical data of 36 children who had been treated at Department of Pediatric Orthopaedics, Medical Center, The Second Affiliated Hospital, Inner Mongolia Medical University from January 2011 to January 2021 for humeral supracondylar fractures with callus formation and displacement neglected for over 1 week. There were 22 boys and 14 girls, with an age of (6.7±2.7) years (from 2.3 to 12.8 years). All fractures were Gartland type Ⅲ. The patients were divided into 2 groups according to their treatment methods: a closed reduction and percutaneous pinning (CRPP) group of 15 patients subjected to the CRPP treatment only, and a leverage group of 21 patients subjected to CRPP assisted by the "lever technique" with posterior elbow Kirschner wire prying and pulling. The 2 groups were compared in terms of operation time, fluoroscopy frequency, quality of reduction, and recovery time for elbow range of motion; the elbow range of motion, visual analogue scale (VAS), Mayo elbow performance score (MEPS) and complications were assessed at the last follow-up.Results:The 2 groups were comparable because there was no significant difference between them in the general information before operation ( P>0.05). All patients were followed up for (26.2±16.3) months (from 6 to 96 months). All the fractures obtained acceptable reduction and clinical union 4 to 6 weeks after operation. The operation time [(28.2±6.8) min] and fluoroscopy frequency [(27.0±6.0) times] in the leverage group were significantly less than those in the CRPP group [(40.8±10.8) min and (43.3±11.4) times] ( P<0.05). The CRPP group was significantly better than the leverage group in the intraoperative Baumann angle (78.1°±1.6° versus 73.7°±4.1°), lateral capitellohumeral angle (58.3°±2.6° versus 49.6°±5.2°) and horizontal rotation rate (109.5%±3.0% versus 103.2%±4.9%) ( P<0.05). The intraoperative reduction in the CRPP group was significantly closer to the normal mean value than that in the leverage group ( P<0.05). There was no significant difference in the recovery time for elbow range of motion between the CRPP and the leverage groups ( P>0.05). At the last follow-up, the Baumann angle (75.4°±2.8°) and the lateral capitellohumeral angle (53.2°±3.6°) in the leverage group were still significantly better than those in the CRPP group (78.3°±1.5° and 57.5°±2.3°) ( P<0.05). However, there was no significant difference in the elbow range of motion, VAS, MEPS or incidence of complications between the 2 groups ( P>0.05). Conclusion:To treat humeral supracondylar fractures with callus formation and displacement neglected for over 1 week in children, CRPP assisted by the "lever technique" with posterior elbow Kirschner wire prying and pulling is an efficient and accurate method, because it can lead to more satisfactory reduction than CRPP only.

Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly (version 2023) / 中华创伤杂志

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Preparation of an online teaching readiness scale for higher education teachers / 中华医学教育探索杂志

This study summarizes related studies on readiness for online teaching in China and globally and constructs an online teaching readiness scale for higher education teachers with reference to related studies on online teaching competency, blended teaching readiness, and influencing factors for online teaching. This scale includes five dimensions, i.e., belief, teaching readiness, technical readiness, online communication readiness, and institutional support. A questionnaire survey and statistical analyses were performed to investigate the rationality of the scale, and then the scale was modified. The results show that the indicators of the scale have a good degree of fitting, and this study provides a necessary standard for examining the online teaching readiness of higher education teachers and new ideas for online teaching in colleges and universities.

Survey on use demands of wise classroom for medical students based on learning experience / 中华医学教育探索杂志

The objectives of the paper is to more accurate understand the use demands of wise classrooms for medical students, and provide scientific basis for wise classroom managers when formulating wise classroom environment optimization strategies. In the paper, the questionnaire survey method was used to investigate 23 indicators in 4 dimensions of hardware facilities, information technology, teaching methods and medical wise classroom features. And the data of 1 074 questionnaires were analyzed using KANO model analysis technology and satisfaction importance quadrant chart. Among the 23 demand indicators, there are 6 required attributes, 7 expected attributes, 9 charm attributes and 1 non-differential attribute. According to the theoretical importance ranking of the KANO model, wise classroom managers should first improve the quality of indicators related to necessary attributes, give priority to the quality of indicators related to expected attributes, and finally meet the requirements of indicators related to charm attributes. Relevant policies and construction suggestions for smart classrooms are put forward from the three levels of school top-level design, teachers and managers in the paper.

Research on the quality certification standard of medical MOOC in universities / 中华医学教育探索杂志

The medical massive open online course (MOOC) quality certification standard is the reference for the implementation of medical MOOC quality monitoring. This thesis utilizes data mining, quantitative analysis, qualitative analysis and other methods, taking the comment text of the Chinese medicine courses on the Ai Course (MOOC of China Universities) platform as the data source out of which to extract certain potential indicators for the medical MOOC quality certification standard. Based on the analysis of the existing research results on MOOC quality evaluation domestic and abroad as well as the relevant policies of the Ministry of Education, a medical MOOC quality accreditation standard including 6 first-level indicators are formed, including course content, teaching design and so on. Expert scores and AHP method were used to calculate the weight coefficient of the quality certification standard. Finally, this paper explains the procedure of medical MOOC quality certification in college. This certification system can be used to conduct self-assessment and quality monitoring of medical MOOC in colleges and universities.

Clinical efficacy of totally laparoscopic pylorus-preserving gastrectomy with preservation of the first branch of the right gastroepiploic vein in the treatment of early gastric cancer / 中华消化外科杂志

Objective:To investigate the clinical efficacy of totally laparoscopic pylorus-preserving gastrectomy (TLPPG) with preservation of the first branch of the right gastroepiploic vein in early gastric cancer (EGC).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 38 EGC patients who were admitted to the Subei Hospital Affiliated to Yangzhou University from July 2018 to May 2021 were collected. There were 18 males and 20 females, aged 60 (range, 39?73) years. All patients underwent TLPPG with preservation of the first branch of the right gastroepiploic vein.Observation indicators: (1) surgical and postoperative condi-tions; (2) postoperative histopathological examination. (3) follow-up. Follow-up was conducted using outpatient examination, WeChat interview and medical record review to detect the nutritional status, residual stomach function, cholecystolithiasis, tumor recurrence and metastasis and death of patients. Follow-up was up to July 2022. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical and postoperative conditions. All 38 patients underwent TLPPG with preservation of the first branch of the right gastroepiploic vein successfully, without laparotomy conversion. The operation time, volume of intraoperative blood loss, time to postoperative first flatus, time to postoperative first liquid food intake and duration of postoperative hospital stay of the 38 patients were (180±28)minutes, (58±38)mL, (2.7±0.6)days, (3.4±0.7)days and (10.3±2.8)days, respectively. Of the 38 patients, there were 6 cases with postoperative complications ≥grade Ⅱ of Clavien-Dindo classification. (2) Postoperative histopatho-logical examination. The tumor diameter, distance from proximal resection margin to tumor and distance from distal resection margin to tumor of the 38 patients were (1.8±0.5)cm, (3.4±0.2)cm and (4.3±0.4)cm, respectively. Both of proximal and distal resection margin was negative. Numbers of lymph node examined and numbers of lymph node examined in the No.6 lymph node of the 38 patients were 23.3±3.9 and 3.4±1.1, respectively. There were 38 cases with pathological T1 stage including 23 cases of T1a stage and 15 cases of T1b stage. There were 36 cases with pathological N0 stage and 2 cases with pathological N1 stage. There were 36 cases with pathological ⅠA stage and 2 cases with pathological ⅠB stage of TNM staging. (3) Follow-up. All 38 patients were followed up for 18(range, 12?48)months. The hemoglobin, serum albumin and total serum protein of the 38 patients were (125.4±5.8)g/L, (42.4±2.3)g/L and (71.6±2.1)g/L, respectively, at postoperative 6 month. Endo-scopy was used to evaluate the function of residual stomach of patients at postoperative 12 month. There were 4 patients with moderate amount of food remaining in the residual stomach. No patient suffered reflux esophagitis, reflux gastritis and bile reflux. None of the 38 patients received post-operative chemotherapy, and there was no tumor recurrence and metastasis or death occured in patient.Conclusion:TLPPG with preservation of the first branch of the right gastroepiploic vein is safe and feasible for the treatment of EGC patients with tumor located at 1/3 of the middle segment of stomach.

Effect of 25G+pars plana vitrectomy combined with preoperative intravitreal injection of Conbercept on proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical effect of 25G+pars plana vitrectomy(PPV)combined with preoperative intravitreal injection of conbercept in the treatment of patients with proliferative diabetic retinopathy(PDR), and analyze the influence on visual acuity, central foveal thickness(CMT)and serum vascular endothelial growth factor(VEGF)level.METHODS: A retrospective study was conducted from October 2019 to January 2022. A total of 80 patients(87 eyes)with PDR were divided into the two groups according to the treatment method, with 40 patients(45 eyes)treated with 25G+PPV in the control group, and 40 patients(42 eyes)treated with 25G+PPV combined with preoperative intravitreal injection of conbercept in the observation group. The two groups were compared in terms of the best corrected visual acuity(BCVA), intraocular pressure, CMT and serum VEGF level before treatment and at 2wk, 1 and 3mo after treatment. The patients were followed up for 3mo, with postoperative complications and recurrence recorded.RESULTS: The incidence of intraoperative bleeding in the observation group was significantly lower than that in the control group(P&#x0026;#x003C;0.05). After treatment, the BCVA of the two groups was improved(P&#x0026;#x003C;0.05), CMT and serum VEGF level were decreased(P&#x0026;#x003C;0.05), but there was no significant change in intraocular pressure(P&#x0026;#x003E;0.05). The BCVA and CMT of observation group were lower than those of control group at 1 and 3mo after treatment(P&#x0026;#x003C;0.05). Serum VEGF level in the observation group was lower than that in the control group at 3mo after treatment(P&#x0026;#x003C;0.05). The incidence of complications in observation group(5%)within 3mo after treatment was significantly lower than that in control group(18%; P&#x0026;#x003C;0.05). There was no statistically significant difference in recurrence rate of PDR between the two groups(P&#x0026;#x003E;0.05).CONCLUSION: With few complications, 25G+PPV combined with preoperative intravitreal injection of conbercept is effective in the treatment of patients with PDR, which can better promote postoperative vision recovery, improve macular edema, and reduce serum VEGF level.

Bladder microenvironment actuated proteomotors with ammonia amplification for enhanced cancer treatment

Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications. However, motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging. Herein, swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification. By decomposing urea into carbon dioxide and ammonia, the designed proteomotors are endowed with self-propulsive capability, which leads to improved internalization and enhanced penetration in vitro. As a glutamine synthetase inhibitor, the loaded l-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells, resulting in local ammonia amplification. After intravesical instillation, the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects. We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.

The Dynamics of Dopamine D2 Receptor-Expressing Striatal Neurons and the Downstream Circuit Underlying L-Dopa-Induced Dyskinesia in Rats / 神经科学通报·英文版

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D2 receptor (D2R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D2R+ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D2R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D2-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D2R+ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D2R+ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D2R+ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D2R+ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.

Loss-of-function of zebrafish cdt1 causes retarded body growth and underdeveloped gonads resembling human Meier-Gorlin syndrome / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

染色质许可和DNA复制因子1（Cdt1）是复制起始许可的主要调控因子，也是组成复制前复合物的核心成员。细胞通过依赖Cdt1的波动水平，且在每个周期中通过调节其总量以确保DNA仅复制一次。Cdt1功能缺陷会造成DNA过度复制，最终导致基因组不稳定。虽然酵母中cdt1和人类Meier-Gorlin综合征（MGS）患者中的CDT1已被广泛研究，但缺乏脊椎动物模型。我们发现在硬骨鱼类分支的几个鲤形目物种（包括斑马鱼）中，Cdt1蛋白在其N末端插入一段其他脊椎动物中没有的独特无序序列。通过分析在cdt1基因中携带移码缺失的遗传性斑马鱼突变体（命名为cdt1zju1 ），我们发现突变胚胎虽然几乎无任何早期胚胎表型异常，但成年突变斑马鱼却表现出侏儒症、生存能力降低的症状，以及性腺发育不全且不育。此外，我们同样发现除转录本cdt1-201外，斑马鱼还存在第二个cdt1转录本——cdt1-202，它是通过跳过外显子2产生，这在其他生物中暂无报道。有意思的是cdt1-202在cdt1-201纯合突变体中显著上调。上述研究结果表明，cdt1-202转录本可能可以补偿cdt1-201在早期发育过程中的功能损失，但不能补偿后期生长，这可支持斑马鱼作为研究人类MGS的遗传模型。

Role of TLR4/NF-κB signaling pathway in hydrogen-rich water improving cognitive impairment induced by ionizing radiation in rats / 环境与职业医学

Background In the process of radiotherapy, when radiation kills tumor cells, it inevitably damages normal tissue cells. Objective To investigate the role of Toll-like receptor 4 (TLR4)/nuclear factor−kappa B (NF-κB) signaling pathway in the improvement of cognitive impairment induced by ionizing radiation by hydrogen-rich water before and after whole brain irradiation in rats. Methods Fifteen male SD rats were randomly divided into three groups: control group, irradiated group (IR group), and hydrogen-rich water intervention group (IR+HRW group), with 5 rats in each group. The control group was not irradiated, but was given purified water (20 mL·kg−1) by gavage every day, while the IR group and the IR+HRW group were irradiated with a single dose of 20 Gy. Three days before, 10 min before, and 30 days after irradiation, purified water/hydrogen-rich water (20 mL·kg−1) was given by continuous gavage every day. The general condition of the rats was observed every day, and the body weight were measured on the 7th, 14th, 21st, and 30th days after irradiation. On the 30th day after irradiation, the learning and memory ability of the rats was tested by Morris water maze; the pathological changes of hippocampus were detected by hematoxylin-eosin (HE) staining after sacrificing the rats; the contents of glutathione (GSH), malondialdehyde (MDA), interleukin-1β (IL-1β), and hydroxyl radicals in brain tissues were detected by enzyme linked immunosorbent assay (ELISA); the mRNA and protein expression levels of TLR4, NF-κB, NOD-like receptor pyrin domain 3 (NLRP3), and cysteinyl aspartate specific proteinase 1 (Caspase 1) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting in the hippocampus of rats. Results After irradiation, the rats in the IR group showed symptoms such as head hair removal and salivation, while the symptoms of the rats in the IR+HRW group were milder. No animal died in the control and the IR+HRW groups, while one rat died in the IR group. From day 14 to day 30 after irradiation, the body weight of the rats in the IR+HRW group tended to be higher than that in the IR group, but the difference was not statistically significant (P>0.05). The Morris water maze results showed that the escape latency of the IR+HRW group was shortened compared with that of IR group from day 1 to day 5 except day 3, but the difference was not statistically significant (P>0.05). For the rats in the IR+HRW group, it took less time to reach the original location of the platform after removing the platform on day 6 and the number of crossing the platform and the residence time in the original platform quadrant increased (P<0.05). The HE staining showed that the number of hippocampal cells in the IR+HRW group was slightly reduced and arranged neatly, without obvious nuclear hyperchromatic and pyknotic phenomenon. The ELISA results showed that the MDA and hydroxyl radical levels were decreased in the IR+HRW group compared with the IR group (P<0.05), the GSH content was increased, and the IL-1β concentration was decreased, but the differences were not statistically significant (P>0.05). The results of qRT-PCR showed that the mRNA expression levels of TLR4 and Caspase 1 in the hippocampus of the IR+HRW group were decreased compared with the IR group (P<0.05), and the mRNA expression levels of NF-κB and NLRP3 were also decreased, but the differences were not statistically significant (P>0.05). The results of Western blotting showed that the expression levels of TLR4 and Caspase 1 protein in the hippocampus of the IR+HRW group were decreased compared with the IR group (P<0.05), and the expression levels of NF-κB p65 and NLRP3 protein were also decreased, but the differences were not statistically significant (P>0.05). Conclusion Hydrogen-rich water can improve cognitive impairment induced by ionizing radiation in rats, and its mechanism may be related to regulating TLR4/NF-κB signaling pathway, inhibiting inflammatory factors, and attenuating oxidative stress.

Effect of hydrogen-rich water on brain injury in rats with acute radiation based on PI3K/AKT/Caspase-9 signaling pathway / 环境与职业医学

Background At present, radiation therapy is widely used in clinical treatment of tumors. However, while radiation therapy damages tumor cells, it also injures surrounding normal tissues. Studies have shown that hydrogen is a potential radiation-protective agent. Objective To investigate the neuroprotective mechanisms of hydrogen-rich water activating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/cysteinyl aspartate specificproteinase-9 (Caspase-9) signaling pathway in acute radiation-induced brain injury. Methods Forty male SD rats were randomly divided into four groups: control group, irradiation only group (IR), high-dose hydrogen-rich water intervention group (IR+HHRW), and low-dose hydrogen-rich water intervention group (IR+LHRW), 10 rats in each group. Except for the control group, animals in each group received a single 20 Gy whole brain irradiation. Animals in all groups were gavaged once a day from 3 d before irradiation to 7 d after irradiation, pure water (20 mL·kg−1) was given to the control and the IR groups, and hydrogen-rich water (20 mL·kg−1, 10 mL·kg−1) was given to the IR+HHRW and the IR+LHRW groups. After 7 d of intervention, 5 rats in each group were selected for the Morris water maze experiment for behavioral evaluation. Autopsies were conducted after anesthesia for the remaining animals and blood samples were collected for hematological analysis. Rat brains were harvested for TUNEL staining to observe neuronal apoptosis. HE staining was performed to observe histopathological changes, enzyme-linked immunosorbent assay was adopted to detect oxidative stress-related indicators, and real-time PCR and Western blotting were used to measure the expressions of PI3K/AKT/Caspase-9 pathway-related genes and proteins. Results The body weight of rats receiving irradiation decreased after 7 d of irradiation compared with the control group (P<0.05), and the symptoms such as arched back and malaise occurred to varying degrees, and the symptoms of rats in the IR+HHRW group were significantly milder than those in the IR group. The behavioral test results showed that the escape latency of rats in the IR+HHRW group or the IR+LHRW group was shorter than that in the IR group from day 2 to day 5 (P<0.05), and it took less time for rats in the IR+HHRW group to reach the original position after removing the platform on day 6 (P<0.05). The hematological test results showed that red blood cell (RBC) count, hemoglobin (HGB) level, and white blood cell (WBC) count were significantly decreased in the IR group (P<0.05), and the changes in the IR+HHRW group were improved (P<0.05). The HE staining results showed that the number of abnormal nerve cells, broken and dissolved nuclei, and the degree of damage in the IR+HHRW group were significantly reduced than those in the IR group. The results of oxidative stress evaluation showed that the ability of the IR group to inhibit free radicals decreased, the level of malondialdehyde (MDA) increased (P<0.01); the MDA level decreased after LHRW intervention (P<0.05); the SOD activity was elevated after HHRW intervention (P<0.05). The TUNEL staining results showed that the apoptosis signals in the IR+HHRW group were sparser than those in the IR group (P<0.05). The real-time PCR results showed that compared with the IR group, the mRNA expression levels of PI3K and AKT in the IR+HHRW group and the IR+LHRW group increased (P<0.05), while the mRNA expression levels of Cytc and Caspase-9 decreased (P<0.05). The Western blotting results showed that compared with the IR group, the phospho-AKT (pAKT) protein expression level in the IR+HHRW group increased significantly (P<0.05), while the expression of Caspase-9 and Cytc proteins decreased significantly (P<0.05). Conclusion Hydrogen-rich water can significantly reduce inflammation and oxidative stress caused by acute irradiation-induced brain injury, and decrease neuronal apoptosis. The mechanism may be related to the PI3K/AKT/Caspase-9 signaling pathway.

Accuracy of three-dimensional periodontal ligament models generated using cone-beam computed tomography at different resolutions for the assessment of periodontal bone loss / 대한치과교정학회지

Objective@#To develop a method for generating three-dimensional (3D) digital models of the periodontal ligament (PDL) using 3D cone-beam computed tomography (CBCT) reconstruction and to evaluate the accuracy and agreement of the 3D PDL models in the measurement of periodontal bone loss. @*Methods@#CBCT data collected from four patients with skeletal Class III malocclusion prior to periodontal surgery were reconstructed at three voxel sizes (0.2 mm, 0.25 mm, and 0.3 mm), and 3D tooth and alveolar bone models were generated to obtain digital PDL models for the maxillary and mandibular anterior teeth. Linear measurements of the alveolar bone crest obtained during periodontal surgery were compared with the digital measurements for assessment of the accuracy of the digital models. The agreement and reliability of the digital PDL models were analyzed using intra- and interexaminer correlation coefficients and Bland–Altman plots. @*Results@#Digital models of the maxillary and mandibular anterior teeth, PDL, and alveolar bone of the four patients were successfully established. Relative to the intraoperative measurements, linear measurements obtained from the 3D digital models were accurate, and there were no significant differences among different voxel sizes at different sites. High diagnostic coincidence rates were found for the maxillary anterior teeth. The digital models showed high intra- and interexaminer agreement. @*Conclusions@#Digital PDL models generated by 3D CBCT reconstruction can provide accurate and useful information regarding the alveolar crest morphology and facilitate reproducible measurements. This could assist clinicians in the evaluation of periodontal prognosis and establishment of an appropriate orthodontic treatment plan.