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This study combined the herbal pair Platycodonis Radix-Curcumae Rhizoma(PR-CR) possessing an inhibitory effect on tumor cell proliferation and metastasis with the active component of traditional Chinese medicine(TCM) silibinin-loaded nanoparticles(NPs) with a regulatory effect on tumor microenvironment based on the joint effect on tumor cells and tumor microenvironment to inhi-bit cell metastasis. The effects of PR-CR on the cellular uptake of NPs and in vitro inhibition against breast cancer proliferation and metastasis were investigated to provide an experimental basis for improving nanoparticle absorption and enhancing therapeutic effects. Silibinin-loaded lipid-polymer nanoparticles(LPNs) were prepared by the nanoprecipitation method and characterized by transmission electron microscopy. The NPs were spherical or quasi-spherical in shape with obvious core-shell structure. The mean particle size was 107.4 nm, Zeta potential was-27.53 mV. The cellular uptake assay was performed by in vitro Caco-2/E12 coculture cell model and confocal laser scanning microscopy(CLSM), and the results indicated that PR-CR could promote the uptake of NPs. Further, in situ intestinal absorption assay by the CLSM vertical scanning approach showed that PR-CR could promote the absorption of NPs in the enterocytes of mice. The inhibitory effect of NPs on the proliferation and migration of 4T1 cells was analyzed using 4T1 breast cancer cells and co-cultured 4T1/WML2 cells, respectively. The results of the CCK8 assay showed that PR-CR-containing NPs could enhance the inhibition against the proliferation of 4T1 breast cancer cells. The wound healing assay indicated that PR-CR-containing NPs enhanced the inhibition against the migration of 4T1 breast cancer cells. This study enriches the research on oral absorption of TCM NPs and also provides a new idea for utilizing the advantages of TCM to inhibit breast cancer metastasis.
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Humans , Mice , Animals , Female , Silymarin/therapeutic use , Caco-2 Cells , Polymers/chemistry , Nanoparticles/chemistry , Cell Line, Tumor , Breast Neoplasms/pathology , Tumor MicroenvironmentABSTRACT
Suppressor APC domain containing 2 (SAPCD2) gene may affect tumor proliferation, invasion, migration and apoptosis, and participate in tumor-related signal pathway transduction, suggesting that SAPCD2 may be a biomarker of tumor and a potential target for treatment. Therefore, SAPCD2 has been widely concerned by researchers. This article reviews the role and related mechanisms of SAPCD2 in tumors.
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Objective:To explore the influencing factors of severe pneumonia in children with respiratory syncytial virus (RSV) infection.Methods:A retrospective case-control study was used to collect 210 children with RSV infected pneumonia admitted to Hebei Children′s Hospital from October 2017 to October 2020. Among them, 70 children with severe pneumonia were included in the severe pneumonia group, and 140 children with common pneumonia were included in the common pneumonia group; the baseline data and relevant laboratory indicators of the two groups were compared; Logistic regression was used to analyze the influencing factors of severe pneumonia in children infected with RSV.Results:The proportions of wheezing, congenital heart disease, respiratory failure, heart failure and pleural effusion of children in severe pneumonia group were higher than those in common pneumonia group, and the forced vital capacity (FVC) and forced expiratory volume in the first second (FEV 1) were lower than those in common pneumonia group (all P<0.05); the levels of C-reactive protein (CRP), CD8 + cells, RSV load and Beclin-1 in severe pneumonia group were higher than those in common pneumonia group, and the levels of CD4 + cells and 1, 25-dihydroxyvitamin D [1, 25-(OH) 2D] were lower than those in common pneumonia group (all P<0.05). After treatment, the levels of CRP, CD8 + cells and Beclin-1 in children with severe pneumonia were lower than those before treatment, and the levels of CD4 + cells and 1, 25-(OH) 2D were higher than those before treatment (all P<0.05). Multiple regression model analysis was established. The results showed that congenital heart disease, high CRP level, high CD8 + cells, high RSV load and high Beclin-1 level were risk factors for severe pneumonia in children with RSV infected pneumonia (all OR>1, P<0.05), and high CD4 + cells and 1, 25-(OH) 2D level were protective factors (all OR<1, P<0.05). Conclusions:Severe pneumonia in children with RSV infected pneumonia may be affected by congenital heart disease, CRP, CD4 + cells, CD8 + cells, 1, 25-(OH) 2D, RSV load and Beclin-1.
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DNA barcoding has been widely used for herb identification in recent decades,enabling safety and innovation in the field of herbal medicine.In this article,we summarize recent progress in DNA bar-coding for herbal medicine to provide ideas for the further development and application of this tech-nology.Most importantly,the standard DNA barcode has been extended in two ways.First,while conventional DNA barcodes have been widely promoted for their versatility in the identification of fresh or well-preserved samples,super-barcodes based on plastid genomes have rapidly developed and have shown advantages in species identification at low taxonomic levels.Second,mini-barcodes are attractive because they perform better in cases of degraded DNA from herbal materials.In addition,some mo-lecular techniques,such as high-throughput sequencing and isothermal amplification,are combined with DNA barcodes for species identification,which has expanded the applications of herb identification based on DNA barcoding and brought about the post-DNA-barcoding era.Furthermore,standard and high-species coverage DNA barcode reference libraries have been constructed to provide reference se-quences for species identification,which increases the accuracy and credibility of species discrimination based on DNA barcodes.In summary,DNA barcoding should play a key role in the quality control of traditional herbal medicine and in the international herb trade.
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With the rapid development of healthcare big data and artificial intelligence technology, how to utilize the massive medical data generated based on clinical diagnosis and treatment has become an important issue to be solved in the field of clinical research. Clinical diagnosis and treatment data is an essential part of healthcare big data, and also the main field of healthcare big data research. With the continuous deepening and extensive development of informatization, hospitals have accumulated a large number of patient-centered clinical diagnosis and treatment data. Deeply mining and analyzing these data through big data technology can provide reference for precise diagnosis and treatment, and standardized prevention and control of diseases. However, conducting relevant research still faces many difficulties and blockages, such as the increased risk of data leakage or abuse, and the difficulty in implementing informed consent. To safely, legally and efficiently utilize clinical diagnosis and treatment data to conduct clinical research and fully tap into the value of these precious medical resources, a tertiary hospital in Beijing has built a research big data platform and developed relevant systems to effectively solve the problems of blockages and difficulties in the application of rich clinical resources to clinical research, and improve the service quality of medical institutions and the conversion rate of scientific research achievements. By introducing the key points and management methods in the implementation of clinical research based on the scientific research big data platform, analyzing and exploring the existing problems and improvement measures, this paper aimed to provide theoretical basis and system reference for high-quality and efficient health and medical big data clinical research, inspire and promote the continuous improvement of medical research management, and promote the development of medical and health science and technology innovation.
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Objective:This paper aims to promote the standardization of ethics review of horizontal scientific research projects and improve the ethics review quality by analyzing the current ethics review practice in a certain tertiary hospital, identifying common problems during the review process, illustrating relevant causes and proposing corresponding solutions.Methods:Through introducing the current situation of ethics review of horizontal scientific research projects in a tertiary level hospital, the differences between the main points of ethics review of horizontal scientific research projects and government-funded scientific research projects were analyzed, so as to sort out the common problems and possible causes in the process of ethics review of horizontal scientific research projects, and then explore the possible corresponding solutions.Results:Based on the characteristics of horizontal research projects, ethics review should focus on their scientific and social values, potential conflicts of interest, protection of subjects′ rights and interests, and whole-process management and quality assurance. At present, there are still many problems, such as a large number of projects, but not many projects with high research value, inadequate project process management, and ineffective implementation of ethics review opinions.Conclusions:The hospital should further improve the management system of horizontal scientific research project approval, bring in more comprehensive review regarding to both scientific and ethics review, engage more experts at the outset of project funding decision-making, set up ethics specialists, strengthen the process management of horizontal scientific research projects, strengthen ethical publicity and education, and improve the ethical awareness of researchers to fully protect the rights and interests of subjects and promote the high-quality development of clinical research.
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To report the short-term clinical outcome of three cases of distal tibial osteosarcoma treated with a novel 3D-printed ankle fusion prosthesis for limb preservation. The patients were admitted to the Department of Bone Tumor, Shanghai General Hospital from January 2020 to June 2021, with one male and two female cases, aged 18, 12, and 14 years, respectively, all diagnosed with distal tibial osteosarcoma (Ennecking stage IIb). A new self-designed ankle fusion prosthesis was used to perform osteosarcoma resection and prosthetic reconstruction of the distal tibia. The operation time, blood loss, postoperative American Orthopedic Foot and Ankle Society Score (AOFAS) and ankle range of motion were recorded. All the 3 patients successfully completed the operation and were followed up for 22 months, 18 months and 12 months, respectively. The operation time was 140 min, 110 min and 200 min, and the blood loss was 200 ml, 200 ml and 350 ml, respectively. At the last follow-up, the AOFAS were 86, 90 and 95 points, and the range of motion of ankle flexion and extension were 30°, 15° and 30°. There was no local recurrence or lung metastasis at the last follow-up. The novel 3D-printed ankle fusion prosthesis in the distal tibia is safe and effective for the reconstruction of bone defects after resection of osteosarcoma in the distal tibia, and the early postoperative function is satisfactory.
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Objective:To explore the construction and application methods of multicenter bone tumor-specific database.Methods:Experts from multiple centers including Shanghai General Hospital, Shanghai Changzheng Hospital, Zhongshan Hospital, Shanghai Sixth People's Hospital, Ruijin Hospital, Fudan University Shanghai Cancer Center and Shanghai Ninth People's Hospital established a standard dataset for bone tumors through research and discussion. Clinical data will be automatically collected and standardized according to standard fields. A database will be built and a users' interface will be developed to ensure secure data storage, while providing services such as exporting raw data, visualizing statistical analysis, establishing clinical queue research projects, et al. Finally, the bone tumor database will be shared by integrating with the Shenkang's Big Data Platform to achieve multi-center data integration.Results:A standard data set for bone tumors containing 603 fields has been established and published. An automated data collection system for bone tumors has been established, including complete data collection, data collation and visualization functions. The data categories include modules such as patients' electronic case information, laboratory information on blood routine, biochemistry and tumor markers, imaging information, surgery information, pathology information and radiotherapy records. Personal information such as patients' names and ID numbers are desensitized and encrypted and can be exported for further research. From 2015 to 2023, the total number of bone tumor cases collected in the database was 10,789. From 2015 to 2019, 112 cases of the osteosarcoma cohort were retrospectively analyzed for admission, with a statistical 5-year survival rate of 68%.Conclusion:A regional bone tumor specialty big data network and data sharing platform has been established, along with data sharing mechanisms and standards including data standards, security standards, and quality evaluation standards. This provides data and efficient new solutions for the construction of China's bone tumor database, as well as a research and development platform for standardized diagnosis and treatment of bone tumors and new technologies.
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@#Lung is one of the most common metastatic organs of carcinomas. Pulmonary metastasectomy has become a common procedure in thoracic surgery and its effectiveness has been demonstrated by many researches. Once the malignant tumor is combined with lung metastasis, which belongs to the category of advanced tumor, surgical resection is only a palliative treatment to reduce the tumor load. However, there are still some controversies among the surgical indications, preoperative examinations, surgical methods and resection ranges, lymph node management, recurrence and re-resection of metastatic tumor and prognostic factors. This article reviews pulmonary metastasectomy from the above aspects.
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@#Objective To compare the clinical effects of lobectomy and sublobar resection in the treatment of lung metastasis and to analyze the factors affecting patient prognosis. Methods A retrospective analysis was performed on the clinical data of 165 patients with pulmonary metastasis who underwent thoracic surgery at the Affiliated Tumor Hospital of Xinjiang Medical University between March 2010 and May 2021, including 67 males and 98 females, with a median age of 52 (44, 62) years. According to the operation methods, patients were divided into a lobectomy group and a sublobar resection group. The clinical data of the patients were compared between the two groups. The Cox proportional hazard model was used for univariate and multivariate analyses. Results The 3- and 5-year overall survival rates were 60.0% and 34.3%, respectively, and the median survival time was 24 months. The 3- and 5-year disease-free survival rates were 39.4% and 23.7%, respectively. Compared with the lobectomy group, the sublobar resection group had shorter operation time for pulmonary metastases (P<0.001), less intraoperative blood loss (P<0.001), less drainage volume on the first day after surgery (P<0.001), less incidence of prolonged air leak (P=0.004), shorter drainage tube indwelling time (P=0.002), and shorter postoperative hospital stay (P=0.023). The disease-free survival time after sublobar resection and lobectomy was 26 months and 24 months, respectively, with no statistical difference (P=0.970). The total survival time of the two groups was 73 months and 69 months, respectively, with no significant difference (P=0.697). Multivariate analysis showed that sex [HR=0.616, 95%CI (0.390, 0.974), P=0.038], disease-free interval [HR=1.753, 95%CI (1.082, 2.842), P=0.023], and postoperative adjuvant therapy [HR=2.638, 95%CI (1.352, 5.147), P=0.004] were independent influencing factors for disease-free survival of patients who underwent pulmonary metastasectomy. Disease-free interval [HR=2.033, 95%CI (1.062, 3.894), P=0.032] and preoperative carcinoembryonic antigen level [HR=2.708, 95%CI (1.420, 5.163), P=0.002] were independent factors influencing the overall survival of patients in this group. Conclusion Sublobar resection provides a safe and effective treatment option for patients with pulmonary metastasis on the premise of ensuring R0 resection of lung metastasis. Sex, disease-free interval, preoperative carcinoembryonic antigen level, and adjuvant therapy after pulmonary metastasectomy are the independent influencing factors for the prognosis.
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OBJECTIVE@#To improve the classical 4-vessel occlusion (4VO) model established by Pulsinelli and Brierley.@*METHODS@#Thirty-two male SD rats were randomized into sham operation group, I4VO-Con10 group, I4VO-Int10 group and I4VO-Int15 group. The sham surgery group underwent exposure of the bilateral vertebral arteries and carotid arteries without occlusion to block blood flow. The I4VO-Con10 group experienced continuous ischemia by occluding the bilateral vertebral arteries and carotid arteries for 10 minutes followed by reperfusion for 24 hours. The I4VO-Int10 and I4VO-Int15 groups were subjected to intermittent ischemia. The I4VO- Int10 group underwent 5 minutes of ischemia, followed by 5 minutes of reperfusion and another 5 minutes of ischemia, and then reperfusion for 24 hours. The I4VO-Int15 group experienced 5 minutes of ischemia followed by two cycles of 5 minutes of reperfusion and 5 minutes of ischemia, and then reperfusion for 24 hours. The regional cerebral blood flow (rCBF) was monitored with laser Doppler scanning, and survival of the rats was observed. HE staining was used to observe hippocampal pathologies to determine the optimal method for modeling. Another 48 rats were randomized into 6 groups, including a sham operation group and 5 model groups established using the optimal method. The 5 I4VO model groups were further divided based on the reperfusion time points (1, 3, 7, 14, and 28 days) into I4VO-D1, I4VO-D3, I4VO-D7, I4VO- D14, and I4VO- D28 groups. Body weight changes and survival of the rats were recorded. HE staining was used to observe morphological changes in the hippocampal, retinal and optic tract tissues. The Y-maze test and light/dark box test were used to evaluate cognitive and visual functions of the rats in I4VO-D28 group.@*RESULTS@#Occlusion for 5 min for 3 times at the interval of 5 min was the optimal method for 4VO modeling. In the latter 48 rats, the body weight was significantly lower than that of the sham-operated rats at 1, 3, 7, 14 and 28 days after modeling without significant difference in survival rate among the groups. The rats with intermittent vessel occlusion exhibited progressive deterioration of hippocampal neuronal injury and neuronal loss. Cognitive impairment was observed in the rats in I4VO-D28 group, but no obvious ischemic injury of the retina or the optic tract was detected.@*CONCLUSION@#The improved 4VO model can successfully mimic the main pathological processes of global cerebral ischemia-reperfusion injury without causing visual impairment in rats.
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Rats , Male , Animals , Rats, Sprague-Dawley , Brain Ischemia , Cerebral Infarction , Reperfusion Injury , Body WeightABSTRACT
OBJECTIVE@#To analyze the composition, incidence and clinical characteristics of oral and maxillofacial infections in oral emergency.@*METHODS@#A retrospective study on patients with oral and maxillofacial infections who visited the Department of Oral Emergency in Peking University School and Hospital of Stomatology from January 2017 to December 2019 was conducted. General characteristics, such as disease composition, gender, age distribution and position of involved teeth were analyzed.@*RESULTS@#A total of 8 277 patients with oral and maxillofacial infections were finally collected, including 4 378 male patients (52.9%) and 3 899 female patients (47.1%), with gender ratio of 1.12:1. The common diseases were periodontal abscess (3 826 cases, 46.2%), alveolar abscess (3 537 cases, 42.7%), maxillofacial space infection (740 cases, 9.0%), sialadenitis (108 cases, 1.3%), furuncle & carbuncle (56 cases, 0.7%) and osteomyelitis (10 cases, 0.1%). Male patients were more easily affected by periodontal abscess, space infection and furuncle & carbuncle than female patients with the gender ratios 1.24:1, 1.26:1, 2.50:1 individually, while the incidence of alveolar abscess, sialadenitis, furuncle & carbuncle had no significant gender difference. Different diseases were prone to occur at different ages. The peak ages of alveolar abscess were 5-9 and 27-67 years, while the peak age of periodontal abscess was 30-64 years. Space infection tended to occur between 21-67 years. There were 7 363 patients with oral abscess (3 826 patients with periodontal abscess and 3 537 patients with alveolar abscess), accounting for 88.9% of all the patients with oral and maxillofacial infections, involving 7 999 teeth, including 717 deciduous teeth and 7 282 permanent teeth. Periodontal abscess usually occurred in permanent teeth, especially the molar teeth. Alveolar abscess may occur in both primary teeth and permanent teeth. In primary teeth, the most vulnerable sites were primary molar teeth and maxillary central incisors while in permanent teeth the most vulnerable sites were first molar teeth.@*CONCLUSION@#Understanding the incidence of oral and maxillofacial infection was conducive to the correct diagnosis and effective treatment of clinical diseases, as well as targeted education for patients of different ages and genders to prevent the occurrence of diseases.
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Humans , Male , Female , Animals , Adult , Middle Aged , Abscess , Retrospective Studies , Periodontal Abscess , Carbuncle , Furunculosis , Incisor , Sialadenitis/epidemiologyABSTRACT
Objective: Through comparative analysis of the disease burden of occupational pneumoconiosis in Gansu Province from 2010 to 2020, the main influencing factors are screened, and scientific basis is provided for rational allocation of limited health resources, precise management and policy implementation. Methods: In August 2021, survey and collect information on surviving occupational pneumoconiosis patients and dead occupational pneumoconiosis patients diagnosed in Gansu Province from 2010 to 2020, and analyze and calculate indicators such as morbidity, mortality, and disability adjusted of life years (DALY). Analyzing the influencing factors of disease burden usirrg multiple linear regression. Results: From 2010 to 2020, the average annual incidence of occupational pneumoconiosis in Gansu Province was 0.9992/100000, the average annual mortality was 0.897/100000, the cumulative case fatality rate was 25.75%, and the cumulative DALY was 28932.96 person-years. The first stage of occupational pneumoconiosis was the highest among DALY loss (19920.14 person-years), and the DALY loss was positively correlated with the stage of occupational pneumoconiosis. Among occupational pneumoconiosis in Gansu Province, silicosis (13753.66 person-years) and coal worker's pneumoconiosis (13414.73 person-years) caused the highest disease burden, followed by cement pneumoconiosis and asbestos lung. Period, length of service, type of disease, and region are all influencing factors of DALY loss (P<0.05). Conclusion: From 2010 to 2020, the DALY losses caused by occupational pneumoconiosis in Gansu Province showed a fluctuating decrease, with the composition of DALY mainly changing from the loss of life years due to premature death to the loss of years due to injury and disability.
Subject(s)
Humans , Pneumoconiosis/epidemiology , Silicosis/epidemiology , Anthracosis/epidemiology , Asbestos , Cost of Illness , China/epidemiologyABSTRACT
Glioblastoma is the most common primary cranial malignancy, and chemotherapy remains an important tool for its treatment. Sanggenon C(San C), a class of natural flavonoids extracted from Morus plants, is a potential antitumor herbal monomer. In this study, the effect of San C on the growth and proliferation of glioblastoma cells was examined by methyl thiazolyl tetrazolium(MTT) assay and 5-bromodeoxyuridinc(BrdU) labeling assay. The effect of San C on the tumor cell cycle was examined by flow cytometry, and the effect of San C on clone formation and self-renewal ability of tumor cells was examined by soft agar assay. Western blot and bioinformatics analysis were used to investigate the mechanism of the antitumor activity of San C. In the presence of San C, the MTT assay showed that San C significantly inhibited the growth and proliferation of tumor cells in a dose and time-dependent manner. BrdU labeling assay showed that San C significantly attenuated the DNA replication activity in the nucleus of tumor cells. Flow cytometry confirmed that San C blocked the cell cycle of tumor cells in G_0/G_1 phase. The soft agar clone formation assay revealed that San C significantly attenuated the clone formation and self-renewal ability of tumor cells. The gene set enrichment analysis(GSEA) implied that San C inhibited the tumor cell division cycle by affecting the myelocytomatosis viral oncogene(MYC) signaling pathway. Western blot assay revealed that San C inhibited the expression of cyclin through the regulation of the MYC signaling pathway by lysine demethylase 4B(KDM4B), which ultimately inhibited the growth and proliferation of glioblastoma cells and self-renewal. In conclusion, San C exhibits the potential antitumor activity by targeting the KDM4B-MYC axis to inhibit glioblastoma cell growth, proliferation, and self-renewal.
Subject(s)
Humans , Glioblastoma/genetics , Bromodeoxyuridine/therapeutic use , Signal Transduction , Proto-Oncogene Proteins c-myc/metabolism , Agar , Cell Proliferation , Cell Line, Tumor , Apoptosis , Jumonji Domain-Containing Histone Demethylases/metabolismABSTRACT
Oxidative stress plays a crucial role in cadmium (Cd)-induced myocardial injury. Mitsugumin 53 (MG53) and its mediated reperfusion injury salvage kinase (RISK) pathway have been demonstrated to be closely related to myocardial oxidative damage. Potentilla anserina L. polysaccharide (PAP) is a polysaccharide with antioxidant capacity, which exerts protective effect on Cd-induced damage. However, it remains unknown whether PAP can prevent and treat Cd-induced cardiomyocyte damages. The present study was desgined to explore the effect of PAP on Cd-induced damage in H9c2 cells based on MG53 and the mediated RISK pathway. For in vitro evaluation, cell viability and apoptosis rate were analyzed by CCK-8 assay and flow cytometry, respectively. Furthermore, oxidative stress was assessed by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining and using superoxide dismutase (SOD), catalase (CAT), and glutathione/oxidized glutathione (GSH/GSSG) kits. The mitochondrial function was measured by JC-10 staining and ATP detection assay. Western blot was performed to detect the expression of proteins related to MG53, the RISK pathway, and apoptosis. The results indicated that Cd increased the levels of reactive oxygen species (ROS) in H9c2 cells. Cd decreased the activities of SOD and CAT and the ratio of GSH/GSSG, resulting in decreases in cell viability and increases in apoptosis. Interestingly, PAP reversed Cd-induced oxidative stress and cell apoptosis. Meanwhile, Cd reduced the expression of MG53 in H9c2 cells and inhibited the RISK pathway, which was mediated by decreasing the ratio of p-AktSer473/Akt, p-GSK3βSer9/GSK3β and p-ERK1/2/ERK1/2. In addition, Cd impaired mitochondrial function, which involved a reduction in ATP content and mitochondrial membrane potential (MMP), and an increase in the ratio of Bax/Bcl-2, cytoplasmic cytochrome c/mitochondrial cytochrome c, and Cleaved-Caspase 3/Pro-Caspase 3. Importantly, PAP alleviated Cd-induced MG53 reduction, activated the RISK pathway, and reduced mitochondrial damage. Interestingly, knockdown of MG53 or inhibition of the RISK pathway attenuated the protective effect of PAP in Cd-induced H9c2 cells. In sum, PAP reduces Cd-induced damage in H9c2 cells, which is mediated by increasing MG53 expression and activating the RISK pathway.
Subject(s)
Cadmium/metabolism , Caspase 3/metabolism , Potentilla/metabolism , Glycogen Synthase Kinase 3 beta/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Cytochromes c/metabolism , Glutathione Disulfide/pharmacology , Oxidative Stress , Myocytes, Cardiac , Reactive Oxygen Species/metabolism , Reperfusion Injury/metabolism , Apoptosis , Polysaccharides/pharmacology , Adenosine Triphosphate/metabolismABSTRACT
Objective To investigate the efficacy and safety of lenvatinib combined with sintilimab as the second-line therapy for advanced intrahepatic cholangiocarcinoma (ICC). Methods A retrospective analysis was performed for the clinical data of the patients with advanced ICC who were admitted to Beijing Ditan Hospital from October 31, 2019 to October 31, 2021 and could not undergo surgery or experienced metastasis after surgery. All patients were treated with lenvatinib combined with sintilimab as the second-line therapy. The patients were followed up, and the RECIST1.1 criteria were used to assess treatment outcome. The primary endpoint was time to progression (TTP), and the secondary endpoints were tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS) time, and safety. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison between groups. Results A total of 27 patients were enrolled, among whom there were15 male patients (55.6%) and 12 female patients (44.4%), with a median age of 58 years (range 33-73 years). The median TTP for these patients was 5.5 (95% confidence interval [ CI ]: 1.7-9.3) months, and 13 patients (48.1%) died of disease progression, with a median OS time of 11.2 (95% CI : 5.0-17.4) months. The overall ORR and DCR were 40.7% and 70.3%, respectively. Of all patients, 66.7% experienced varying degrees of adverse events, and among these patients, 44.4% had an increase in alanine aminotransferase, 44.4% had an increase in aspartate aminotransferase, 37.0% had hypertension, 29.6% had an increase in bilirubin, 29.6% experienced diarrhea, and 25.9% each experienced proteinuria, anorexia, and weakness. No treatment-related death was observed, and only 1 patient developed grade Ⅳ immune-related hepatotoxicity and was relieved without sequelae after corticosteroid therapy, resulting in permanent withdrawal of sintilimab. The patients with lymph node metastasis had a significantly shorter median TTP than those without lymph node metastasis (4.5 months vs 18.8 months, P =0.035), and the patients who achieved disease remission had a significantly longer median TTP [11.6 months (95% CI : 5.6-17.6) vs 2.8 months (95% CI : 1.8-3.8), P < 0.001]; the patients with lymph node metastasis had a shorter median OS time [9.6 months (95% CI: 7.9-11.3) vs 21.9 months (95% CI : 0-44.9), P =0.053], and the patients who achieved disease remission had a significantly longer median OS time [16.6 months (95% CI : 9.0-24.2) vs 6.9 months (95% CI : 3.6-10.2), P =0.011]. Conclusion Lenvatinib combined with sintilimab has a marked clinical effect and a low incidence rate of serious adverse events as the second-line therapy for advanced ICC, and therefore, it is a safe and effective treatment regimen.
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Objective To investigate the value of interleukin-6 (IL-6) combined with Model for End-stage Liver Disease (MELD) score in predicting the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 86 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2018 were enrolled, and according to their survival status after follow-up for 90 days, they were divided into death group with 50 patients and survival group with 36 patients. ELISA was used to measure the serum level of IL-6, and a statistical analysis was performed for general information. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Pearson correlation analysis was performed for IL-6 and other variables; a binary logistic regression analysis was used to investigate the independent risk factors for the prognosis of patients with HBV-ACLF; the receiver operating characteristic (ROC) curve was used to assess the value of IL-6 combined with MELD score in predicting the prognosis of HBV-ACLF. Results There were significant differences between the death group and the survival group in hematocrit ( t =2.413), platelet count ( t =6.584), total bilirubin (TBil) ( t =-8.070), prothrombin time (PT) ( U =77.500), international standardized ratio ( U =102.000), HBV DNA ( t =-2.767), IL-6 ( t =-16.543), and MELD score ( t =-8.192), and the death group had a significantly higher level of IL-6 than the survival group (27.13±12.18 pg/mL vs 9.72±5.56 pg/mL, P < 0.001). The Pearson correlation analysis showed that IL-6 was positively correlated with TBil and PT ( r =0.579 and 0.681, both P < 0.001). The binary logistic regression analysis showed that IL-6 (odds ratio[ OR ]=1.480, 95% confidence interval [ CI ]: 1.196~1.833, P =0.007) and MELD score ( OR =1.128, 95% CI : 1.033~1.231, P < 0.001) were independent risk factors for the death of HBV-ACLF patients within 90 days. IL-6 combined with MELD score had an area under the ROC curve (AUC) of 0.891 (95% CI : 0.778~0.999), with a higher AUC than IL-6 (AUC=0.838, 95% CI : 0.687~0.989) or MELD score (AUC=0.783, 95% CI : 0.634~0.933). IL-6 combined with MELD score had a significantly higher value than IL-6 alone in predicting the prognosis of patients with HBV-ACLF ( Z =-2.257, P =0.024). Conclusion IL-6 combined with MELD score can be used as a good model for predicting the short-term prognosis of patients with HBV-ACLF.
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Objective: To investigate the changes of heparin-binding protein (HBP) in severe burn patients during shock stage and its effects on human umbilical vein endothelial cells (HUVECs) and neutrophils in vitro. Methods: Prospective observational and experimental research methods were used. Twenty severe burn patients who met the inclusion criteria and were admitted to the Department of Burns and Plastic Surgery of Affiliated Suzhou Hospital of Nanjing Medical University from August to November 2020 were included in severe burn group (12 males and 8 females, aged 44.5 (31.0, 58.0) years). During the same period, 20 healthy volunteers with normal physical examination results in the unit's Physical Examination Center were recruited into healthy control group (13 males and 7 females, aged 39.5 (26.0, 53.0) years). Enzyme-linked immunosorbent assay (ELISA) method was used to detect the protein expression levels of HBP and tissue inhibitor of metalloproteinase 1 (TIMP-1) in plasma of patients within 48 hours after injury in severe burn group and in plasma of volunteers in healthy control group. The correlation between protein expression of HBP and that of TIMP-1 in the plasma in the two groups was analyzed by Pearson correlation analysis. The fourth passage of HUVECs in logarithmic growth phase were used for the experiment. The HUVECs were divided into normal control group with routine culture (the same treatment below) and recombinant HBP (rHBP)-treated 12 h group, rHBP-treated 24 h group, and rHBP-treated 48 h group with corresponding treatment according to the random number table (the same grouping method below), and the mRNA expression of TIMP-1 in cells was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. The HUVECs were divided into normal control group and rHBP-treated 48 h group with corresponding treatment, and the protein expression of TIMP-1 in the cells was detected by Western blotting. The HUVECs were divided into normal control group, rHBP alone group, aprotinin alone group, and rHBP+aprotinin group treated with the corresponding reagents (with the final molarity of rHBP being 200 nmol/L and the final concentration of aprotinin being 20 μg/mL, respectively), cultured for 48 h, and ELISA was used to detect the protein expression of TIMP-1 in the culture supernatant of cells. The neutrophils were isolated from the peripheral venous blood of the aforementioned 10 healthy volunteers by immunomagnetic bead sorting, and the cells were divided into normal control group, recombinant TIMP-1 (rTIMP-1) alone group, phorbol acetate (PMA) alone group, and rTIMP-1+PMA group treated with corresponding reagents (with the final concentration of rTIMP-1 being 500 ng/mL and the final molarity of PMA being 10 nmol/L, respectively). After being cultured for 1 h, the expression of CD63 protein in cells was detected by immunofluorescence method, the positive expression rate of CD63 protein in cells was detected by flow cytometry, and the protein expression levels of HBP and myeloperoxidase (MPO) in the culture supernatant of cells were detected by ELISA. The normal control group underwent the above-mentioned related tests at appropriate time points. The number of samples was 3 in each group of cell experiment. Data were statistically analyzed with chi-square test, Mann-Whitney U test, Kruskal-Wallis H test, and Tamhane's T2 test. Results: The protein expression levels of HBP and TIMP-1 in the plasma of patients in severe burn group were 404.9 (283.1, 653.2) and 262.1 (240.6, 317.4) ng/mL, respectively, which were both significantly higher than 61.6 (45.0, 68.9) and 81.0 (66.3, 90.0) ng/mL of volunteers in healthy control group (with Z values of -5.41 and -5.21, respectively, P<0.01). The correlation between the protein expression of HBP and that of TIMP-1 in the plasma of volunteers in healthy control group was not strong (P>0.05). The protein expression of HBP was significantly positively correlated with that of TIMP-1 in the plasma of patients in severe burn group (r=0.64, P<0.01). Compared with that in normal control group, the mRNA expression of TIMP-1 in HUVECs was significantly increased in rHBP-treated 12 h group, rHBP-treated 24 h group, and rHBP-treated 48 h group (with t values of -3.58, -2.25, and -1.26, respectively, P<0.05). Western blotting detection showed that compared with that in normal control group, the protein expression of TIMP-1 in HUVECs in rHBP-treated 48 h group was significantly enhanced. After 48 h of culture, compared with that in normal control group, the protein expression level of TIMP-1 in the culture supernatant of HUVECs in rHBP alone group was significantly increased (t=9.43, P<0.05), while the protein expression level of TIMP-1 in the culture supernatant of HUVECs didn't change significantly in aprotinin alone group or rHBP+aprotinin group (P>0.05); compared with that in rHBP alone group, the protein expression level of TIMP-1 in the culture supernatant of HUVECs in rHBP+aprotinin group was significantly decreased (t=4.76, P<0.01). After 1 h of culture, the trend of CD63 protein expression in neutrophils detected by immunofluorescence method and that by flow cytometry were consistent in each group. After 1 h of culture, compared with that in normal control group, the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells in rTIMP-1 alone group all had no significant changes (P>0.05), while the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells were all significantly increased in PMA alone group and rTIMP-1+PMA group (with t values of 2.41, 3.82, 5.73, 1.05, 4.16, and 1.08, respectively, P<0.05 or P<0.01); compared with that in PMA alone group, the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells in rTIMP-1+PMA group were all significantly decreased (with t values of 5.26, 2.83, and 1.26, respectively, P<0.05 or P<0.01). Conclusions: The expression level of HBP in the plasma of severe burn patients is increased during shock stage. HBP can induce HUVECs to secrete TIMP-1 in vitro, and TIMP-1 can reduce the expression of CD63 molecule in human neutrophils.
Subject(s)
Adult , Female , Humans , Male , Antimicrobial Cationic Peptides , Blood Proteins , Burns , Human Umbilical Vein Endothelial Cells , Neutrophils , Tissue Inhibitor of Metalloproteinase-1ABSTRACT
Neutrophils have always been considered as a short-lived and homogeneous cell type in the innate immune system, which have limited pro-inflammatory or anti-inflammatory effects. However, in recent 10 years, the understanding of neutrophils has been undergoing some kind of revival as researches progressed. The researches on the heterogeneity of neutrophils and the mechanism of their interaction with other immune cells have promoted the researchers to re-understand the physiological and pathophysiological roles of neutrophils. In the following decades, with the development of single-cell sequencing technology, spatial transcriptome sequencing technology, and multi-omics combined sequencing technology, researchers will have a better understanding of the biological behaviors of neutrophils. This paper briefly reviews the biological behaviors of neutrophils and their roles in various diseases in recent years.
Subject(s)
NeutrophilsABSTRACT
Objective To investigate the efficacy and safety of lenvatinib in patients with unresectable hepatocellular carcinoma (HCC) previously treated with tyrosine kinase inhibitor (TKI). Methods A retrospective analysis was performed for the clinical data of 76 patients with unresectable HCC who were treated with lenvatinib in Beijing Ditan Hospital, Capital Medical University, from January 2019 to January 2020, and according to the treatment method, they were divided into TKI previously untreated group with 49 patients and TKI treatment-experienced group with 27 patients. The patients were observed till one year after enrollment, adjustment of treatment regimen, tumor progression, or death. The two groups were compared in terms of progression-free survival (PFS) time, objective response rate (ORR), disease control rate (DCR), and incidence rate of adverse events. The t -test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test or the Wilcoxon rank-sum test was used for comparison of categorical data between two groups; the Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison between groups. Results There were no significant differences between the TKI previously untreated group and the TKI treatment-experienced group in median PFS time (115 days vs 72 days, P =0.148), ORR (36.7% vs 18.5%, P =0.098), DCR (65.3% vs 55.6%, P =0.402), and incidence rates of grade ≥3 adverse events (24.5% vs 18.5%, P =0.550). Conclusion Patients with unresectable HCC previously treated with TKI can benefit from lenvatinib and have good safety, with similar results to those treated with TKI for the first time.