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.

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.

Study on the method of automatically determining maxillary complex landmarks based on non-rigid registration algorithms / 中华口腔医学杂志

Objective: To explore an automatic landmarking method for anatomical landmarks in the three-dimensional (3D) data of the maxillary complex and preliminarily evaluate its reproducibility and accuracy. Methods: From June 2021 to December 2022, spiral CT data of 31 patients with relatively normal craniofacial morphology were selected from those who visited the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. The sample included 15 males and 16 females, with the age of (33.3±8.3) years. The maxillary complex was reconstructed in 3D using Mimics software, and the resulting 3D data of the maxillary complex was mesh-refined using Geomagic software. Two attending physicians and one associate chief physician manually landmarked the 31 maxillary complex datasets, determining 24 anatomical landmarks. The average values of the three expert landmarking results were used as the expert-defined landmarks. One case that conformed to the average 3D morphological characteristics of healthy individuals' craniofacial bones was selected as the template data, while the remaining 30 cases were used as target data. The open-source MeshMonk program (a non-rigid registration algorithm) was used to perform an initial alignment of the template and target data based on 4 landmarks (nasion, left and right zygomatic arch prominence, and anterior nasal spine). The template data was then deformed to the shape of the target data using a non-rigid registration algorithm, resulting in the deformed template data. Based on the unchanged index property of homonymous landmarks before and after deformation of the template data, the coordinates of each landmark in the deformed template data were automatically retrieved as the automatic landmarking coordinates of the homonymous landmarks in the target data, thus completing the automatic landmarking process. The automatic landmarking process for the 30 target data was repeated three times. The root-mean-square distance (RMSD) of the dense corresponding point pairs (approximately 25 000 pairs) between the deformed template data and the target data was calculated as the deformation error of the non-rigid registration algorithm, and the intra-class correlation coefficient (ICC) of the deformation error in the three repetitions was analyzed. The linear distances between the automatic landmarking results and the expert-defined landmarks for the 24 anatomical landmarks were calculated as the automatic landmarking errors, and the ICC values of the 3D coordinates in the three automatic landmarking repetitions were analyzed. Results: The average three-dimensional deviation (RMSD) between the deformed template data and the corresponding target data for the 30 cases was (0.70±0.09) mm, with an ICC value of 1.00 for the deformation error in the three repetitions of the non-rigid registration algorithm. The average automatic landmarking error for the 24 anatomical landmarks was (1.86±0.30) mm, with the smallest error at the anterior nasal spine (0.65±0.24) mm and the largest error at the left oribital (3.27±2.28) mm. The ICC values for the 3D coordinates in the three automatic landmarking repetitions were all 1.00. Conclusions: This study established an automatic landmarking method for three-dimensional data of the maxillary complex based on a non-rigid registration algorithm. The accuracy and repeatability of this method for landmarking normal maxillary complex 3D data were relatively good.

Advances in algorithms for three-dimensional craniomaxillofacial features construction based on point clouds / 中华口腔医学杂志

In light of the increasing digitalization of dentistry, the automatic determination of three-dimensional (3D) craniomaxillofacial features has become a development trend. 3D craniomaxillofacial landmarks and symmetry reference plane determination algorithm based on point clouds has attracted a lot of attention, for point clouds are the basis for virtual surgery design and facial asymmetry analysis, which play a key role in craniomaxillofacial surgery and orthodontic treatment design. Based on the studies of our team and national and international literatures, this article presented the deep geometry learning algorithm to determine landmarks and symmetry reference plane based on 3D craniomaxillofacial point clouds. In order to provide reference for future clinical application, we describe the development and latest research in this field, and analyze and discuss the advantages and limitations of various methods.

The design method of the digital sequential tooth-sectioning guide for the extraction of mandibular impacted third molars / 中华口腔医学杂志

Objective: To explore a method for digitally designing and fabricating a sequential tooth-sectioning guide that can assist in the extraction of mandibular horizontal impacted third molars, preliminarily evaluate its feasibility and provide a reference for clinical application. Methods: Twenty patients with mandibular low level impacted third molars who visited the Department of General Dentistry, Peking University School and Hospital of Stomatology from March 2021 to January 2022 were selected. Cone-beam CT showed direct contact between the roots and mandibular canal, and full range impressions of the patients' intraoral teeth were taken and optical scans of the dental model were performed. The patients' cone-beam CT data and optical scan data were reconstructed in three dimensions, anatomical structure extraction, registration fusion, and the design of the structure of the guide (including crown-sectioning guide and root-sectioning guide) by Mimics 24.0, Geomagic Wrap 2021, and Magics 21.0 software, and then the titanium guide was three dimension printed, and the guide was tried on the dental model. After confirmation, the guide was used to assist the dentist in the operation. We observed whether the guide was in place, the number of tooth splitting, the matching of tooth splitting with the preoperative design, the operation time, and whether there were any complications. Results: In this study, 20 sectioning guides were successfully printed, all of them were well fitted in the patients' mouth, the average number of section was 3.4 times, the tooth parts was better matched with the preoperative design, and the average operative time of the guides was (29.2±9.8) minutes without complications such as perforation of the bone cortex. Conclusions: The use of sequential sectioning guides to assist in the extraction of mandibular impacted third molars was initially validated to accurately replicate the preoperative sectioning design, and is expected to provide a digital solution to improve surgical precision and ensure safety. Further studies with larger sample sizes are needed to evaluate its accuracy and safety.

Preliminary study on three-dimensional morphological reconstruction method for external nose defect based on three-dimensional face template / 中华口腔医学杂志

Objective: To provide a new solution for the digital design of nasal prostheses, this study explores the three-dimensional (3D) facial morphology completion method for external nasal defects based on the non-rigid registration process of 3D face template. Methods: A total of 20 male patients with tooth defect and dentition defect who visited the Department of Prosthodontics, Peking University School and Hospital of Stomatology from June to December 2022 were selected, age 18-45 years old. The original 3D facial data of patients were collected, and the 3D facial data of the external nose defect was constructed in Geomagic Wrap 2021 software. Using the structured 3D face template data constructed in the previous research of the research group, the 3D face template was deformed and registered to the 3D facial data of external nose defect (based on the morphology of non-defective area) by non-rigid registration algorithm (MeshMonk program), and the personalized deformed data of the 3D face template was obtained, as the complemented facial 3D data. Based on the defect boundary of the 3D facial data of the external nose defect, the complemented external nose 3D data can be cut out from the complemented facial 3D data. Then the nasofacial angle and nasolabial angle of the complemented facial 3D data and the original 3D facial data was compared and analyzed, the ratio between the nose length and mid-face height, nose width and medial canthal distance of the complemented facial 3D data was measured, the edge fit between the edge curve of the complemented external nose 3D data and the defect edge curve of the 3D facial data of external nose defect was evaluated, and the morphological difference of the nose between the complemented external nose 3D data and the original 3D facial data was analyzed. Results: There was no significant statistically difference (t=-0.23, P=0.823; Z=-1.72, P=0.086) in the nasofacial angle (28.2°±2.9°, 28.4°±3.5° respectively) and nasolabial angle [95.4°(19.2°), 99.9°(9.5°) respectively] between the 20 original 3D facial data and the complemented facial 3D data. The value of the ratio of nose length to mid-face height in the complemented facial 3D data was 0.63±0.03, and the value of the ratio of nose width to medial canthal distance was 1.07±0.08. The curve deviation (root mean square value) between the edge curve of the complemented external nose 3D data and the defect edge curve of the 3D facial data of external nose defect was (0.37±0.09) mm, the maximum deviation was (1.14±0.32) mm, and the proportion of the curve deviation value within±1 mm was (97±3)%. The distance of corresponding nose landmarks between the complemented facial 3D data and the original 3D facial data were respectively, Nasion: [1.52(1.92)] mm; Pronasale: (3.27±1.21) mm; Subnasale: (1.99±1.09) mm; Right Alare: (2.64±1.34) mm; Left Alare: (2.42± 1.38) mm. Conclusions: The method of 3D facial morphology completion of external nose defect proposed in this study has good feasibility. The constructed complemented external nose 3D data has good facial coordination and edge fit, and the morphology is close to the nose morphology of the original 3D facial data.

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.

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.

Risk factors for contralateral anterior cruciate ligament injury after primary anterior cruciate ligament reconstruction / 中国修复重建外科杂志

OBJECTIVE@#To investigate the risk factors of contralateral anterior cruciate ligament (ACL) injury after primary ACL reconstruction.@*METHODS@#A retrospective review was conducted on the 716 patients with ACL injury who received primary ACL reconstruction surgery and met the selection criteria between January 2012 and September 2018. After a mean follow-up period of 7.6 years (range, 4-10 years), 65 patients (9.1%) experienced contralateral ACL injury (injured group) and 651 patients (90.9%) did not (uninjured group). There was no significant difference in age, body mass index, and preoperative Lachman test degree between groups ( P>0.05). However, the proportion of female in the injured group was significantly higher than that of male ( P<0.05), and the preoperative posterior tibial slope (PTS) was significantly higher than that of the uninjured group ( P<0.05). Using the outcome of contralateral ACL injury as the dependent variable, the clinical data of the patient was first used as the independent variable, and univariate COX regression was used to analyze the prognostic influencing factors. Then, the indicators with differences in univariate COX regression were used as the independent variable, and multivariate COX regression was used to analyze the independent risk factors affecting prognosis. Log-Rank (Mantel-Cox) test was used to test and analyze the occurrence time of contralateral ACL injury in patients of different genders; X-tile software was used to analyze the occurrence time of contralateral ACL injury in patients with different PTS using Log-Rank (Mantel-Cox) test and PTS cut-off values.@*RESULTS@#Univariate COX regression analysis showed that gender and PTS were influence factors for contralateral ACL injury ( P<0.05); further multivariate COX regression analysis showed that female and increased PTS were independent risk factors for contralateral ACL injury ( P<0.05). The Log-Rank (Mantel-Cox) test results showed that the contralateral ACL injury occurred in female at 8.853 (8.600, 9.106) years, which was significantly shorter than that in male [9.661 (9.503, 9.819) years] ( χ 2=20.323, P<0.001). Using X-tile software to analyze the cut-off value of PTS, it was found that the cut-off value of PTS for contralateral ACL injury was 10.92°. According to the Log-Rank (Mantel-Cox) test, it was found that the contralateral ACL injury occurred in 5.762 (4.981, 6.543) years in patients with PTS≥10.92°, which was significantly shorter than patients with PTS<10.92° [9.751 (9.650, 9.853) years]( χ 2 =302.479, P<0.001).@*CONCLUSION@#Female and PTS≥10.92° after primary ACL reconstruction are independent risk factors for contralateral ACL injury.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine： Sjögren's Syndrome / 中国实验方剂学杂志

Sjögren's syndrome （SS）， a disorder of immune system， is one of the dominant diseases treated by traditional Chinese medicine （TCM）. China Association of Chinese Medicine organized experts in the field of TCM and western medicine rheumatology and pharmacology to discuss the advantages and optimal regimens of TCM for the treatment of SS. The experts generally agreed on the low early diagnosis rate of SS and the lack of targeted therapeutic drugs. In addition， autoimmune abnormality is the key factor in the occurrence of SS and deficiency of both Qi and Yin is the core pathogenesis. SS has unique tongue manifestations， which is expected to allow for the early diagnosis and treatment with integrated traditional Chinese and western medicine. TCM has advantages in treating SS in terms of alleviating clinical symptoms and systemic involvement， individualized treatment， relieving sleep and mood disorders， preventing the occurrence in the early stage， and enhancing the effectiveness and reducing toxicity in the treatment by integrated TCM and western medicine. In general， TCM has advantages in different stages of SS. Internal and external use of TCM， acupuncture， and acupotome are all available options. The optimal regimens should be determined on the basis of pattern identification， stage of disease， and the advantages of TCM. Clinical characteristics and biomarkers of SS should be studied to classify patients， so as to design precision evidence-based TCM regimens for SS. On the basis of unique tongue manifestations of SS， models for early diagnosis and poor prognosis identification of SS should also be established to achieve early prevention and treatment and to improve the prognosis. In the future， we should vigorously carry out high-quality evidence-based medical research on the treatment of SS by TCM and integrated traditional Chinese and western medicine and develop relevant guidelines to optimize and standardize current diagnosis and treatment， thereby laying a basis for clarifying and explaining the advantages of TCM in treating SS.

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.

IL-33 gene recombination and expression does not affect the phenotypic characteristics of rabies virus in vitro / 细胞与分子免疫学杂志

Objective To create a recombinant rabies virus overexpressing IL-33 and to clarify the effect of IL-33 overexpression on the phenotypic characteristics of recombinant virus in vitro. Methods The IL-33 gene was obtained and amplified from the brain of a highly virulent strain of rabies infected mouse. It was then inserted between the G and L genes of the parental virus LBNSE genome by reversing genetic manipulation and rescuing a recombinant virus overexpressing IL-33. BSR cells or mouse NA cells were infected with recombinant rabies virus (rLBNSE-IL33) and the parental strain LBNSE. Sequencing and fluorescent antibody virus neutralization assay was employed to detect the stability of recombinant virus at multiplicity of infection=0.01. Viral titres focal forming units (FFU) were detected to plot multi-step growth curves (multiplicity of infection=0.01). Cytotoxicity assay kit was used to detect cellular activity. ELISA was adopted to identify the IL-33 in the supernatant of infected cells of different multiplicity of infection. Results Rescued rLBNSE-IL33 overexpressing IL-33 remained stable for at least 10 consecutive generations and had virus titers of approximately 108 FFU/mL. rLBNSE-IL33 was able to express IL-33 at high levels in a dose-dependent manner, but no high expression of IL-33 was detected in the supernatant of cells infected by LBNSE. Examination of the titers of rLBNSE-IL33 and the parental strain LBNSE in BSR and NA cells over 5 days showed no significant differences and similar kinetic properties in growth. Overexpression of IL-33 had no significant effect on the proliferation and activity of infected cells. Conclusion Overexpression of IL-33 does not significantly affect the phenotypic characteristics of recombinant rabies virus in vitro.

Pre-existing cardiometabolic comorbidities and survival of middle-aged and elderly non-small cell lung cancer patients / 老年心脏病学杂志（英文版）

BACKGROUND@#Both lung cancer and cardiometabolic diseases are leading causes of death in China, and they share some common risk factors. However, the prevalence and long-term effect of pre-existing cardiometabolic comorbidities (CMCs) on the survival of middle-aged and elderly lung cancer patients are still not clear.@*METHODS@#We consecutively recruited 3477 non-small cell lung cancer (NSCLC) patients between January 2011 and December 2018 from four cancer specialty hospitals in China. Univariable and multivariable adjusted Cox proportional hazard models were conducted to evaluate the risk factors associated with mortality. Hazard ratio (HR) for mortality and corresponding 95% CI were calculated.@*RESULTS@#The prevalence of CMCs was 30.0% in middle-aged NSCLC patients and 45.5% in elderly NSCLC patients. Log-rank analysis presented statistically significant differences in median survival time between patients with CMCs and without CMCs in both the middle-aged group (21.0 months vs. 32.0 months, P < 0.01) and the elderly group (13.0 months vs. 17.0 months, P = 0.01). Heart failure (HR = 1.754, 95% CI: 1.436-2.144, P < 0.001) and venous thrombus embolism (HR = 2.196, 95% CI: 1.691-2.853, P < 0.001) were independent risk factors for the survival of middle-aged NSCLC patients, while heart failure (HR = 1.709, 95% CI: 1.371-2.130, P < 0.001) continued to decrease overall survival in the elderly group. Hyperlipidemia may be a protective factor for survival in middle-aged group (HR = 0.741, 95% CI: 0.566-0.971, P = 0.030).@*CONCLUSIONS@#Our findings demonstrate for the first time the prevalence and prognostic value of pre-existing CMCs in Chinese middle-aged and elderly NSCLC patients.

Gene cloning and sequence analysis of the RPL29 gene and its effect on lipogenesis in goat intramuscular adipocytes / 生物工程学报

The aim of this study was to clone the goat RPL29 gene and analyze its effect on lipogenesis in intramuscular adipocytes. Using Jianzhou big-eared goats as the object, the goat RPL29 gene was cloned by reverse transcription-polymerase chain reaction (RT-PCR), the gene structure and expressed protein sequence were analyzed by bioinformatics, and the mRNA expression levels of RPL29 in various tissues and different differentiation stages of intramuscular adipocytes of goats were detected by quantitative real-time PCR (qRT-PCR). The RPL29 overexpression vector pEGFP-N1-RPL29 constructed by gene recombination was used to transfect into goat intramuscular preadipocytes and induce differentiation. Subsequently, the effect of overexpression of RPL29 on fat droplet accumulation was revealed morphologically by oil red O and Bodipy staining, and changes in the expression levels of genes related to lipid metabolism were detected by qRT-PCR. The results showed that the length of the goat RPL29 was 507 bp, including a coding sequence (CDS) region of 471 bp which encodes 156 amino acid residues. It is a positively charged and stable hydrophilic protein mainly distributed in the nucleus of cells. Tissue expression profiling showed that the expression level of this gene was much higher in subcutaneous adipose tissue and inter-abdominal adipose tissue of goats than in other tissues (P < 0.05). The temporal expression profile showed that the gene was expressed at the highest level at 84 h of differentiation in goat intramuscular adipocytes, which was highly significantly higher than that in the undifferentiated period (P < 0.01). Overexpression of RPL29 promoted lipid accumulation in intramuscular adipocytes, and the optical density values of oil red O staining were significantly increased (P < 0.05). In addition, overexpression of RPL29 was followed by a highly significant increase in ATGL and ACC gene expression (P < 0.01) and a significant increase in FASN gene expression (P < 0.05). In conclusion, the goat RPL29 may promote intra-muscular adipocyte deposition in goats by up-regulating FASN, ACC and ATGL.

Cloning, identification and functional analysis of the goat transcription factor c-fos / 生物工程学报

C-fos is a transcription factor that plays an important role in cell proliferation, differentiation and tumor formation. The aim of this study was to clone the goat c-fos gene, clarify its biological characteristics, and further reveal its regulatory role in the differentiation of goat subcutaneous adipocytes. We cloned the c-fos gene from subcutaneous adipose tissue of Jianzhou big-eared goats by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed its biological characteristics. Using real-time quantitative PCR (qPCR), we detected the expression of c-fos gene in the heart, liver, spleen, lung, kidney, subcutaneous fat, longissimus dorsi and subcutaneous adipocytes of goat upon induced differentiation for 0 h to 120 h. The goat overexpression vector pEGFP-c-fos was constructed and transfected into the subcutaneous preadipocytes for induced differentiation. The morphological changes of lipid droplet accumulation were observed by oil red O staining and bodipy staining. Furthermore, qPCR was used to test the relative mRNA level of the c-fos overexpression on adipogenic differentiation marker genes. The results showed that the cloned goat c-fos gene was 1 477 bp in length, in which the coding sequence was 1 143 bp, encoding a protein of 380 amino acids. Protein structure analysis showed that goat FOS protein has a basic leucine zipper structure, and subcellular localization prediction suggested that it was mainly distributed in the nucleus. The relative expression level of c-fos was higher in the subcutaneous adipose tissue of goats (P < 0.05), and the expression level of c-fos was significantly increased upon induced differentiation of subcutaneous preadipocyte for 48 h (P < 0.01). Overexpression of c-fos significantly inhibited the lipid droplets formation in goat subcutaneous adipocytes, significantly decreased the relative expression levels of the AP2 and C/EBPβ lipogenic marker genes (P < 0.01). Moreover, AP2 and C/EBPβ promoter are predicted to have multiple binding sites. In conclusion, the results indicated that c-fos gene was a negative regulatory factor of subcutaneous adipocyte differentiation in goats, and it might regulate the expression of AP2 and C/EBPβ gene expression.

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.

Automatic determination of mandibular landmarks based on three-dimensional mandibular average model / 北京大学学报(医学版)

OBJECTIVE@#To explore an efficient and automatic method for determining the anatomical landmarks of three-dimensional(3D) mandibular data, and to preliminarily evaluate the performance of the method.@*METHODS@#The CT data of 40 patients with normal craniofacial morphology were collected (among them, 30 cases were used to establish the 3D mandibular average model, and 10 cases were used as test datasets to validate the performance of this method in determining the mandibular landmarks), and the 3D mandibular data were reconstructed in Mimics software. Among the 40 cases of mandibular data after the 3D reconstruction, 30 cases that were more similar to the mean value of Chinese mandibular features were selected, and the size of the mandibular data of 30 cases was normalized based on the Procrustes analysis algorithm in MATLAB software. Then, in the Geomagic Wrap software, the 3D mandibular average shape model of the above 30 mandibular data was constructed. Through symmetry processing, curvature sampling, index marking and other processing procedures, a 3D mandible structured template with 18 996 semi-landmarks and 19 indexed mandibular anatomical landmarks were constructed. The open source non-rigid registration algorithm program Meshmonk was used to match the 3D mandible template constructed above with the tested patient's 3D mandible data through non-rigid deformation, and 19 anatomical landmark positions of the patient's 3D mandible data were obtained. The accuracy of the research method was evaluated by comparing the distance error of the landmarks manually marked by stomatological experts with the landmarks marked by the method of this research.@*RESULTS@#The method of this study was applied to the data of 10 patients with normal mandibular morphology. The average distance error of 19 landmarks was 1.42 mm, of which the minimum errors were the apex of the coracoid process [right: (1.01±0.44) mm; left: (0.56±0.14) mm] and maximum errors were the anterior edge of the lowest point of anterior ramus [right: (2.52±0.95) mm; left: (2.57±1.10) mm], the average distance error of the midline landmarks was (1.15±0.60) mm, and the average distance error of the bilateral landmarks was (1.51±0.67) mm.@*CONCLUSION@#The automatic determination method of 3D mandibular anatomical landmarks based on 3D mandibular average shape model and non-rigid registration algorithm established in this study can effectively improve the efficiency of automatic labeling of 3D mandibular data features. The automatic determination of anatomical landmarks can basically meet the needs of oral clinical applications, and the labeling effect of deformed mandible data needs to be further tested.