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AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.
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CD47 is a transmembrane protein widely expressed on cell surface, which is considered as a key molecule for immune escape. With an increasing number of related studies, the role of CD47 and its ligands in immunomodulatory effects has been gradually understood. Recent studies have investigated the role of CD47 in ischemia-reperfusion injury of allogenetic kidney transplantation, rejection and xenotransplantation. Nevertheless, the specific role and the key mechanism remain elusive. In this article, the structure and function of CD47, common CD47 ligands, the relationship between CD47 and kidney transplantation, and the application of CD47 in kidney transplantation were reviewed, the latest research progress of CD47 in kidney transplantation was summarized, and the limitations of current research and subsequent research direction were analyzed, aiming to provide reference for subsequent application of CD47 in allogeneic and kidney xenotransplantation.
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Background Tuberculosis is the most common complication of pneumoconiosis, which accelerates the progression of pneumoconiosis. Pneumoconiosis combined with tuberculosis is a major health risk. Objective To understand the outpatient health service utilization for patients of pneumoconiosis combined with tuberculosis and its main influencing factors. Methods A stratified random sampling combined with non-random sampling was used to select 11181 pneumoconiosis patients in 27 provincial administrative regions (excluding Shanghai, Tianjin, Hainan, Tibet Autonomous Region, Taiwan, Hongkong and Macao Special Administrative Regions) from December 2017 to June 2021. A self-constructed questionnaire, i.e. Health Seeking Behaviors of Pneumoconiosis Patients and Their Influencing Factors, was used, which included basic information, outpatient and inpatient service utilization, and influencing factors of medical treatment behaviors of pneumoconiosis patients. The effective recovery rate of the questionnaire was 90.7%. All patients of pneumoconiosis combined with tuberculosis (n=762) were included as the study subjects. The difference of outpatient utilization in the past two weeks, choosing medical institutions, and the reasons of not seeking medical treatment between urban and rural areas, and the influencing factors of outpatient service utilization were analyzed. Results The study subjects were mainly silicosis combined with tuberculosis (502 cases, 65.9%) and coal workers' pneumoconiosis combined with tuberculosis (232 cases, 30.5%), aged (58.6±12.5) years old. The main region was Western China (45.1%), followed by Eastern China (22.1%), Centeral China (20.2%), and Northeastern China (12.6%). The outpatient utilization rate in the past two weeks was 38.5% (293/762), and the main medical institutions consulted were municipal or provincial hospitals (32.0%), district or county hospitals (28.6%), and township hospitals or health service centers (17.5%). Short distance (20.7%), the availability of specialist outpatient services (16.7%), high level of medical care (14.8%), and low medical cost (12.3%) were the main reasons in choosing medical institutions. Higher proportion of patients seeking medical services due to acute exacerbation in rural areas was reported than in urban areas in the past two weeks (P<0.01). In addition to being hospitalized (113 cases, 41.4%) and self-purchasing medicine (46 cases, 16.8%), the reasons for not seeking medical treatment were self-perceived mild symptoms (15.0%) and high medical cost without reimbursement (9.5%). The multiple regression results showed that outpatient rate for patients of pneumoconiosis combined with tuberculosis in the western region was higher than that in the eastern region (OR=1.66, 95%CI: 1.03, 2.68); patients with an annual personal income of 10000-35500 yuan had a higher outpatient rate than the > 35500 yuan income group (OR=2.54, 95%CI: 1.49, 4.36); the outpatient rate of silicosis patients was higher than that of coal workers' pneumoconiosis (OR=1.83, 95%CI: 1.23, 2.72); the outpatient rate of patients with clinically diagnosed cases (no classified stage of pneumoconiosis) was higher than that of patients with stage I pneumoconiosis (OR=2.32, 95%CI: 1.24, 4.31). Exacerbation of pneumoconiosis-related symptoms in past two weeks (OR=4.26, 95%CI: 2.89, 6.28), occupational injury insurance (OR=0.49, 95%CI: 0.30, 0.80), and hospitalization in past one year (OR=2.37, 95%CI: 1.41, 3.97) were the main factors influencing the outpatient health service utilization among patients of pneumoconiosis combined with tuberculosis. Conclusion The outpatient rate of patients of pneumoconiosis combined with tuberculosis is higher than that of patients of pneumoconiosis without tuberculosis. The utilization of outpatient services is related with disease factors and socio-economic security factors.
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Xenotransplantation is an efficient pathway to solve the problem of transplant organ source deficiency in clinical settings. With the increasing progress of gene editing technique and immune suppression regimen, important development has been achieved on researches regarding pig to non-human primate kidney xenotransplantation, which provides a good condition for the introduction of the technique in the clinical application. In view of the substantial difference between human and non-human primate, and to meet the needs of current ethic requirements, it is necessary to perform subclinical studies for pig to human kidney xenotransplantation. In recent years, such subclinical studies with regard to the genetically modified pig to brain death recipient kidney xenotransplantation had been performed, indicating that kidney xenotransplantation gradually began to transit to the clinical development stage. However, donor/recipient selection and immune suppression regimen has not reached a consensus yet, and has to be clarified in subclinical studies. In this article, the current status and confronted problems of donor/recipient selection, immune suppression regimen and post transplantation management in the subclinical studies of kidney xenotransplantation were reviewed, aiming to promote the clinical transformation of kidney xenotransplantation to the clinical application.
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Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.
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Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D3 of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.
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@#Currently, in precision cardiac surgery, there are still some pressing issues that need to be addressed. For example, cardiopulmonary bypass remains a critical factor in precise surgical treatment, and many core aspects still rely on the experience and subjective judgment of cardiopulmonary bypass specialists and surgeons, lacking precise data feedback. With the increasing elderly population and rising surgical complexity, precise feedback during cardiopulmonary bypass becomes crucial for improving surgical success rates and facilitating high-complexity procedures. Overcoming these key challenges requires not only a solid medical background but also close collaboration among multiple interdisciplinary fields. Establishing a multidisciplinary team encompassing professionals from the medical, information, software, and related industries can provide high-quality solutions to these challenges. This article shows several patents from a collaborative medical and electronic information team, illustrating how to identify unresolved technical issues and find corresponding solutions in the field of precision cardiac surgery while sharing experiences in applying for invention patents.
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Objective:Health policy and management, and its development as a discipline, play an important role in promoting the development of medicine; however, where is no scientific and reasonable evaluation system of science and technology in practice.Here we will explore and establish a special evaluation system to this research feild.Methods:To analyze the problems, tasks and unique research methods specially solved and used in the field of health management and policy; to discuss the existing problems with theory combined with practice.Results:According to the guidance of national policy, put forward principles and some assessment indicators with their weight grading, index, and examples in detail for the academic evaluation system in the field of this field.Conclusions:Health policy and management is a kind of discipline of the category of social science that possesed the particularity of practice management. Thus, it is important that the academic evaluation should reflect the responsibilities, contributions and characteristics of this subject and the researchers.
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Objective:To establish the clinical laboratory genetic diagnosis procedures for Marfan syndrome (MFS) and carry out clinical laboratory genetic diagnosis for MFS families.Methods:The second generation high-throughput sequencing was used to sequence and analyze the FBN1 gene of two MFS families who visited to Fuwai Central China Cardiovascular Hospital (Heart Center of Henan People′s Hospital) from January to December 2020, and then Sanger sequencing was used to verify the second generation high-throughput sequencing results. At the same time, the sanger sequencing of mutation sites was performed on normal family members and 100 healthy people to identify the pathogenic mutations of FBN1 gene in the MFS families. The pregnant women of two families were guided for prenatal diagnosis in the second trimester of pregnancy.Results:The clinical laboratory diagnosis of MFS showed that two MFS patients had the pathogenic mutation of c.2560T>C heterozygous mutation and c.6772T>C heterozygous mutation in FBN1 gene, respectively. The mutation was not observed in 100 healthy people and normal members in two families. The prenatal diagnosis showed that there was a heterozygous mutation of FBN1 gene c.2560T>C in the first fetus of the MFS family, which was MFS. There was no mutation in the FBN1 gene in the second fetus of the MFS family, so it was recommended to continue the pregnancy. The results of postpartum follow-up were consistent with the results of clinical laboratory diagnosis.Conclusion:The clinical laboratory genetic diagnosis procedures for MFS have been established successfully, which provides an important reference for clarifying the clinical diagnosis of MFS.
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Objective:To seek any correlation between and prognosis and hospitalization costs of stroke survivors with dysphagia.Methods:The records of 1370 stroke survivors admitted to the rehabilitation departments of 3 public hospitals in Weifang were studied. Of them, 499 (36.4%) were diagnosed with dysphagia and 871 were not. Binary logistic regression and multiple linear regression were employed to analyze the correlation between dysphagia and the occurrence of pneumonia, modified Rankin Scale (mRS) scores, modified Barthel index (MBI) scores, length of stay and total hospitalization cost.Results:After adjusting for confounding factors, the risk of pneumonia in the dysphagia group was 2.4 times higher. At discharge, the risk of an mRS≥3 was 3.3 times greater and that of an MBI score <60 was 1.7 times greater with dysphagia. Multiple stepwise linear regression showed that dysphagia was significantly associated with higher mRS scores at discharge, lower MBI scores, and longer hospital stays. The standardized regression coefficients predict that after the length of stay, dysphagia is the strongest predictor of the cost of hospitalisation, followed by ADL ability, pneumonia, supratentorial, haemorrhagic stroke and CCI.Conclusions:Dysphagia is a significant predictor of the hospitalization costs of stroke patients. It is recommended to identify and treat dysphagia as early as possible to improve the prognosis of such patients and reduce the economic burden.
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Objective:To measure the change in Young′s modulus of the biceps brachii during passive stretching and to assess the potential of shear wave elastography (SWE) as an auxiliary quantitative technique for assessing muscle tone.Methods:Forty-nine stroke survivors and 30 healthy subjects were evaluated using the modified Ashworth scale (MAS). According to their MAS scores they were divided into a healthy group, a healthy elbow group, an MAS class-0 group, an MAS class-1 group, an MAS class-1 + group and an MAS class-2 group. During passive extension of the subjects′ elbows, shear wave elastography was used to image the biceps brachii. Six points of the elbow were selected to record the instantaneous Young′s modulus ( EX) and calculate its change during the movement (Δ E). Those data were correlated with the MAS scores and compared among the groups. Results:Persons with higher MAS scores tended to have a higher Young′s modulus of the biceps brachii, and the modulus was likely to increase more with increases in the angle of elbow extension. From half of the range of motion to full extension there were significant differences in EX and Δ E between MAS class-0 and class-1 groups, as well as between the class-0 and class-1 + groups. There were, however, no significant differences between MAS class-1 and MAS class-1 + . Conclusions:MAS scores can usefully predict biceps brachii stiffness during passive elbow flexion. Shear wave elastography can quantify that stiffness and also muscle tone.
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Objective: To explore the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022. Methods: Real-time PCR and enzyme-linked immunosorbent assay were used to detect viral nucleic acid of Norovirus (NoV), Sappovirus (SaV), Astrovirus (AstV), Enteric Adenovirus (AdV) or antigen of Rotavirus (RV) in 748 stool samples collected from Beijing Capital Institute of Pediatrics from January 2018 to December 2021. Subsequently, the reverse transcription PCR or PCR method was used to amplify the target gene of the positive samples after the initial screening, followed by sequencing, genotyping and evolution analysis, so as to obtain the characteristics of these viruses. Phylogenetic analysis was performed using Mega 6.0. Results: From 2018 to 2021, the overall detection rate of the above five common viruses was 37.6%(281/748)in children under 5 years old in Beijing. NoV, Enteric AdV and RV were still the top three diarrhea-related viruses, followed by AstV and SaV, accounting for 41.6%, 29.2%, 27.8%, 8.9% and 7.5%, respectively. The detection rate of co-infections with two or three diarrhea-related viruses was 4.7% (35/748). From the perspective of annual distribution, the detection rate of Enteric AdV was the highest in 2021, while NoV was predominant in the other 4 years. From the perspective of genetic characteristics, NoV was predominant by GⅡ.4, and after the first detection of GⅡ.4[P16] in 2020, it occupied the first two gene groups together with GⅡ.4[P31]. Although the predominant RV was G9P[8], the rare epidemic strain G8P[8] was first detected in 2021. The predominant genotypes of Enteric AdV and AstV were Ad41 and HAstV-1. SaV was sporadic spread with a low detection rate. Conclusion: Among the diarrhea-related viruses infected children under 5 years of age in Beijing, the predominant strains of NoV and RV have changed and new sub-genotypes have been detected for the first time, while the predominant strains of AstV and Enteric AdV are relatively stable.
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Preescolar , Humanos , Lactante , Beijing/epidemiología , Diarrea/epidemiología , Heces , Norovirus/genética , Filogenia , Rotavirus/genética , Virosis/epidemiología , Virus/genéticaRESUMEN
With the improvement of DNA methylation detection techniques, studies on age-related methylation sites have found more age-specific ones across tissues, which improves the sensitivity and accuracy of age estimation. In addition, the establishment of various statistical models also provides a new direction for the age estimation of tissues from different sources. This review summarizes the related studies of age estimation based on DNA methylation from the aspects of detection technology, age-related cytosine phosphate guanine site and model selection in recent years.
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Metilación de ADN , Genética Forense/métodos , Islas de CpG , Medicina LegalRESUMEN
Trace amines are endogenous molecules distributed in the central nervous system and peripheral tissues that resemble common biogenic amines in terms of subcellular localization, chemical structure, and metabolism. Trace amine-associated receptor (TAAR) is a kind of evolutionarily conserved G-protein-coupled receptors in vertebrates, in which TAAR1 is a functional regulator of monoamine transmitters such as dopamine and serotonin. TAAR1 is widely considered as a potential therapeutic target for schizophrenia, depression and drug addiction. Moreover, TAAR1 is also expressed in peripheral tissues. The homeostasis imbalance of trace aminergic system can induce over-activation of peripheral immune system and central immune inflammatory response. TAAR1 modulators are becoming potential emerging drugs for the treatment of immune-related illnesses, because they may play a major role in the activation or modulation of immune response.
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Animales , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Aminas Biogénicas , Dopamina , Trastornos Relacionados con SustanciasRESUMEN
ObjectiveTo compare the effects of two different insemination methods， conventional in vitro fertilization （IVF） and intracytoplasmic sperm injection （ICSI）， on pregnancy outcomes in patients with frozen-thawed D6（day 6） blastocyst transfer. MethodsA retrospective cohort study was conducted to analyze the clinical data of patients with thawed D6 blastocyst transfer between January 2018 and April 2020 at the Fertility Center of the Third Hospital of Sun Yat-sen University， divided into conventional IVF group （446 cycles ） and ICSI fertilization group （200 cycles） according to the fertilization method. Patients were divided into those with a history of D5（day 5） blastocyst transfer and those without. The patients’ general characteristics， blastocyst quality， and pregnancy outcomes of the two groups were compared. ResultsBMI， years of infertility， and basal FSH were not statistically significant in the IVF and ICSI groups （P > 0.05）. Regardless of the history of D5 transfer， patients in the ICSI group were younger than those in the IVF group （P < 0.001）， the proportion of primary infertility was significantly higher in the ICSI group （P < 0.001）， and the number of oocytes obtained and the number of normally fertilized oocytes in the ICSI group were higher than those in the conventional IVF fertilization group （P < 0.001）. The proportion of stage V and Ⅵ blastocysts was significantly higher in the conventional IVF group than in the ICSI group （21.6 % vs. 3.14 %， P < 0.001）. High-quality blastocysts with an ICM score of A were significantly higher in the ICSI group than in the IVF group （23.8 % vs. 14.3 %， P = 0.01）. The HCG-positive and clinical pregnancy rates were significantly higher in the ICSI group than in the IVF group （65.5 % vs. 48.4 %， P < 0.001； 56 % vs. 41.3 %， P = 0.001）， and embryo implantation and live birth rates were also higher in the ICSI group than in the conventional IVF group （43.8 % vs. 30.9 %， P < 0.001； 43.0 % vs. 31.8 %， P = 0.006）. After correcting for age and number of oocytes obtained between the two groups， the clinical pregnancy rate was still significantly higher in the ICSI group than in the conventional IVF group （OR： 1.590， 95 % CI： 1.030， 2.455， P = 0.036）. Infant birth weight was lower in the ICSI group than in the IVF group （P = 0.016）， and the differences in preterm birth rate， sex ratio， and mode of delivery were not statistically significant between the two groups. ConclusionsClinical pregnancy and live birth rates after thawing and transfer of D6 blastocysts fertilized by ICSI are higher than those of D6 blastocysts fertilized by conventional IVF， which may be related to the different factors contributing to the slow development of blastocysts in patients who received different fertilization methods. The relatively good pregnancy outcome after the transfer of thawed D6 blastocysts fertilized by ICSI may compensate to some extent for the difference in pregnancy outcome due to the relatively slow blastocyst development and a relatively higher proportion of D6 blastocysts after ICSI fertilization in male infertility patients.
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Growing clinical evidence shows that Qufeng Gutong Cataplasm may exert a significant analgesic effect. However, the pharmacological characteristics and mechanisms underlying this prescription are still unclear. In the current study, a "disease-syndrome-symptom-formula" association network analysis was performed to explore the pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm against osteoarthritis (OA), neuropathic pain (NP), chronic inflammatory pain (CIP) and myofascial pain syndrome (MPS) by integrating clinical phenomics data, transcriptomics data and biological interaction network mining. As a result, the three functional modules (Qufeng Sanhan-QFSHG, Shujin Huoxue-SJHXG and Xiaozhong Zhitong-XZZTG) enriched by the drug network targets were all related to the pharmacological effects of Qufeng Gutong Cataplasm, including dispersing cold and relieving pain, activating blood and relieving pain, reducing swelling and relieving pain. In addition, the main pharmacological effects of QFSHG and XZZTG were dispelling wind and dispersing cold and dehumidifying, promoting Qi and reducing swelling and relieving pain, respectively. In terms of reversing the imbalance of "immune-inflammation-vascular axis", the main pharmacological effects of SJHXG were regulating the liver and promoting Qi, activating blood circulation and removing stasis. Mechanically, the key network targets of Qufeng Gutong Cataplasm against OA, NP, CIP and MPS may play a therapeutic role in relieving hyperalgesia and paresthesia by reversing the "neuro-endocrine-immune" imbalance system during the occurrence and progression of diseases. In conclusion, our data indicate that Qufeng Gutong Cataplasm may relieve the pain and wind-cold-dampness arthralgia syndrome related symptoms by regulating the "neuro-endocrine-immune" system, neurological and endocrine disorders and reversing the imbalance of "immunity-inflammation". The relevant results may provide a network-based evidence for clinical positioning of Qufeng Gutong Cataplasm, and offer a direction for further clinical and experimental validation.
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Artesunate possesses the potential of intervening with glioma, however, its pharmacological mechanisms remain unclarified. Firstly, the effects of artesunate on cell activity, proliferation and apoptosis of U87 and U251 human glioma cells were explored. It was found that artesunate exerted stronger inhibitory effects on the activity and proliferation of U87 cells than U251 cells. It could significantly promote apoptosis in U87 cells (P < 0.05), while only high dose of artesunate can promote that of U251 cells (P < 0.01), detected by Hoechst and TUNEL cell apoptosis staining. Further, the differential expression gene sets between artesunate-sensitive and non-sensitive cell line, as well the therapeutic effects-related genes of artesunate were obtained through transcriptome sequencing and differential data analysis by using the lysates of U87 and U251 cells before and after artesunate treatment, aiming to explore the molecular mechanism of distinct artesunate sensitivity to two types of cells. Then, key putative targets that related to therapeutic effects were screened by constructing the interaction network of differential genes of three above comparison groups, and calculating their topological characteristics. Pathway enrichment analysis showed that those key putative targets were significantly enriched in several signaling pathways that were closely associated with the main pathological changes of glioma, among which apoptosis-related activating transcription factor 4 (ATF4)-DNA damage induced transcript 3 (DDIT3)- polyadenosine diphosphate ribose polymerase 1 (PARP1) signaling axis was the most enriched in. Molecular docking indicated that artesunate had fine binding affinities with ATF4 and DDIT3. Above all, this study preliminarily revealed that ATF4-DDIT3-PARP1 signaling axis is the target pathway of artesunate intervening with U87 glioma cells, and PARP1 may be an important gene for U251 cells to develop resistance to artesunate. Our results not only provide fundamental experimental evidence for artesunate as a potential therapeutic drug in glioma treatment, but shed light into overcoming drug resistance in its clinical therapy.
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On the basis of the qualitative preparation quality markers of Zhibao Sanbian Wan (ZBSBW), we screened out the quantitative markers and evaluated the content consistency of ZBSBW. A method capable of simultaneously determining 34 compounds in ZBSBW was established based on HPLC-MS/MS, and 16 batches of ZBSBW were simultaneously analyzed by this method. Furthermore, we explored a general strategy for analyzing the component migration in preparation, plasma, brain tissue and cerebrospinal fluid. The methodological investigation was confirmed by linear range, recovery (85.10%-105.07%), precision (RSD: 1.37%-4.58%), stability, and repeatability (3.00%-12.45%), the established method was suitable for the detection and quantification of the compounds in ZBSBW. The contents of compounds in ZBSBW were all lower than 1 mg·g-1, and the contents and daily dose of nystose were the highest, followed by echinacoside, paeoniflorin, osthole and paeonol. The results of systematic clustering showed that the contents were consistent for ordinary preparations of ZBSBW. The principal component analysis showed that the components of berberine, ginsenoside Re, ginsenoside Rg1, pinoresinol diglucoside and tenuifolin had large variation, which contributed significantly to the grouping. The contents of echinacoside, verbascoside, polygalaxanthone Ⅲ, β-ecdysterone, osthole, alisol B 23-acetate, liquiritin and glycyrrhizic acid were stable from batch to batch. The animal experiment results showed that osthole, paeonol and liquiritin in ZBSBW could be absorbed into the blood and enter the brain tissue by passing through the blood-brain barrier. All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee at Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (No. 2020B071). The above compounds contributed the quantitative preparation quality markers of ZBSBW. In conclusion, the HPLC-MS/MS method established in this study was sensitive, accurate and rapid, and could be used for simultaneous quantification of 34 compounds and content consistency evaluation of multiple batches of preparations in ZBSBW. The result provided a methodological basis for the screening of quantitative preparation quality markers and material basis research of ZBSBW.
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Objective:To investigate the surgical method of LC-II screws for fragility fractures of the pelvis (FFP) in the elderly and evaluate its clinical efficacy.Methods:A retrospective analysis was performed on 45 patients with FFPs operated in our department from January 2011 to January 2022. The clinical information was as follows. The FFP classification of pelvic fracture was IIIA in 26 cases and IIIB in 19 cases. Among them, 22 cases were fixed with closed reduction and modified LC-II screws (experimental group), and 23 cases were fixed with open reduction and reconstruction plates (control group). In the experimental group, there were 6 males and 16 females. The age range was 62-90 years, with an average of 73.2±9.2 years. The FFP classification of pelvic fracture was IIIA in 12 cases and IIIB in 10 cases. In the control group, there were 8 males and 15 females. The age range was 60-87 years, with an average of 72.8±6.6 years. FFP classification of pelvic fracture was IIIA in 14 cases and IIIB in 9 cases. After admission, pelvic X-ray and CT scan were performed, and the surgery was prepared. In the experimental group, after closed reduction of the posterior ring, the modified LC-II screw was inserted below the anterior inferior iliac spine (AIIS) toward the sacroiliac joint and penetrated the sacroiliac joint. For combined anterior ring fractures, the INFIX was used for anterior ring fixation. In the control group, the posterior ring was fixed with a reconstruction plate and/or sacroiliac screw after open reduction through the lateral rectus approach (LRA). The clinical efficacy was evaluated between the experimental group and the control group.Results:All 45 patients were successfully operated and followed up for 6 months to 3 years. All the pelvic fractures healed. In the experimental group of 22 cases, the time from injury to operation was 3-9 days, with an average of 5.8±1.9 days; the operation time was 25-70 min, with an average of 42.0±12.9 min. The intraoperative bleeding was 20-40 ml, with an average of 29.1±6.7 ml. According to the X-ray reduction evaluation criteria of Matta, 7 cases were excellent, 11 cases were good and 4 cases were medium, with an excellent and good rate of 81.8%. According to rehabilitation criteria of Majeed, 10 cases were excellent, 6 cases were good and 6 cases were fair, with a total excellent and good rate of 72.7%. At the last follow-up, sacroiliac joint pain was evaluated by VAS score: 0 in 10 cases, <3 in 7 cases, and 4-6 in 5 cases. No internal fixation loosening occurred. In the control group, the time from injury to operation was 5-20 days, with an average of 9.9±3.8 days; the operation time was 50-150 min, with an average of 89.1±29.5 min; the intraoperative bleeding was 220-1 000 ml, with an average of 509.2±214.3 ml. According to the X-ray reduction evaluation criteria of Matta, 16 cases were excellent, 4 cases were good and 3 cases was medium, with an excellent and good rate of 87.0%. According to rehabilitation criteria of Majeed, 12 cases were excellent, 6 cases were good and 7 cases were fair, with a total excellent and good rate of 78.3%. At the last follow-up, sacroiliac joint pain was evaluated by VAS score: 0 in 14 cases, <3 in 6 cases, and 4-6 in 3 cases. In the control group, posterior ring plate loosening was found in 2 cases and anterior ring pubic ramus plate and screw loosening was found in 4 cases, but there was no reduction loss.Conclusion:The modified LC-II screw is theoretically feasible in the treatment of FFP. Preliminary clinical results show good safety and efficacy, providing a new idea for minimally invasive treatment of FFP.
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Objective:To explore the surgical methods and treatment effects of adult anterior dislocation of the sacroiliac joint (AADSJ).Methods:A multi-center retrospective case series study was conducted to analyze the clinical data of 25 cases admitted in 5 clinical centers (affiliations of authors in this article) from January 2016 to January 2021. There were 18 males and 7 females, aged 38.8±15.5 years (range, 18-83 years). The AADSJ clinical classification system was formulated based on the radiographic morphology of anterior dislocation of the sacroiliac joint, which includes two types. Type I: complete anterior dislocation of the sacroiliac joint, and displacement of the entire iliac auricular surface to the front of the sacrum. Type II: fracture of the sacroiliac joint combined with anterior dislocation, subdivided into 3 subtypes. Type IIa: iliac fracture involves the anterior 1/3 of the sacroiliac joint, and dislocation of the ilium anterior to the sacrum. Type IIb: iliac fracture involves the posterior 2/3 of the sacroiliac joint, and dislocation of the ilium anterior to the sacrum. Type IIc: iliac fracture involves the posterior 2/3 of the sacroiliac joint, and dislocation of the ilium anteromedial to the sacrum. The reliability and repeatability of the clinical classification, Tile classification and Young-Burgess classification were performed based on the results of two-phase assessments in four observers. The operations were performed by the lateral-rectus approach and the ilioinguinal approach. The operation time and intraoperative bleeding were recorded. Pelvic X-ray and CT scan were rechecked after the operation. The quality of fracture reduction was evaluated according to Matta score. The postoperative functional rehabilitation was evaluated according to the Majeed rehabilitation standard at one-year follow-up.Results:Among 25 cases in this study, there were 3 cases of Type I, 5 cases of Type IIa, 9 cases of Type IIb and 8 cases of Type IIc according to the clinical classification system. The Kappa values of reliability tests for the clinical classification, Tile classification and Young-Burgess classification were 0.681, 0.328 and 0.383, respectively. The Kappa values of repeatability tests for the clinical classification, Tile classification and Young-Burgess classification were 0.690, 0.221 and 0.395, respectively. The reliability and repeatability of the AADSJ clinical classification were significantly better than other classifications. There were 14 cases underwent lateral rectus abdominis approach and 11 cases underwent ilioinguinal approach. The operative time for managing anterior dislocation of the sacroiliac joint was 122.0±50.7 min (range, 65-148 min) through the lateral rectus abdominis approach, and through the ilioinguinal approach was 178.0±49.9 min (range, 110-270 min), with a significant difference ( t=2.76, P=0.011). The amount of intraoperative blood loss through the lateral rectus approach was 680±330 ml (range, 350-2,120 ml), which was significantly less than that through the ilioinguinal approach (1,660±968 ml, 680-3,300 ml), with a significant difference ( t=3.55, P=0.002). The follow-up period was 1-3 years. At one week after surgery, the quality of fracture reduction evaluated by Matta score showed that the excellent and good reduction rate of the lateral-rectus approach was 79% (11/14), and that of the ilioinguinal approach was 73% (11/14), with no statistically significant difference ( P=1.000). At a one-year follow-up, according to Majeed's criteria, the overall excellent and good rate of the lateral-rectus approach was 64% (9/14), which is similar to 64% (7/11) of that of the ilioinguinal approach. No fracture reduction loss or internal fixation loosening failure occurred. Conclusion:The AADSJ clinical classification system can accurately describe the imaging features and clinical manifestations of AADSJ, with high reliability and repeatability. The AADSJ can be treated by the lateral-rectus approach or the ilioinguinal approach, with similar therapeutic effects but the former having less trauma.