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Objective:To examine the clinicopathological and molecular pathological characteristics of patients with colorectal cancer(CRC)who have mutations in the POLE and POLD1 genes.Methods:In this study, we retrospectively collected data from 276 middle-aged and elderly patients aged 45 years and over who were diagnosed with colorectal cancer at Beijing Hospital between October 2020 and September 2022.We utilized next generation sequencing and bioinformatics analysis to screen for harmful germline and somatic mutations in the POLE and POLD1 genes.The study involved 276 patients, who were divided into three groups based on their genetic mutations.The deleterious mutation group had 6 cases, the mutation of unknown significance group had 18 cases, and the wild type group had 252 cases.We also collected clinical and pathological features of the patients and analyzed their correlation with other molecular pathological results such as tumor mutation burden(TMB), microsatellite instability(MSI), and gene co-mutation.Results:No germline mutations were detected in the POLE and POLD1 genes across all patients.Out of the 276 patients, 18(6.5%)were found to carry POLE mutations.Among these, 6(2.2%)were classified as deleterious mutations, 12(4.3%)were positive for POLE mutations of unknown significance, and the remaining patients had wild type POLE genes.Out of the 276 patients, POLD1 gene mutations of unknown significance were found in 10 patients(3.6%). Among the 276 patients, 5 cases(1.8%)carried two types of gene mutations.Patients in the deleterious mutation group showed earlier tumor stage( P<0.05)and a higher prevalence of low-grade tumor budding( P<0.05), with 6 patients being affected by this.Compared to the wild type group, colon cancer patients showed a higher frequency of deleterious mutations and variants of unknown significance in the poorly differentiated group( P<0.05). The median TMB in the deleterious mutation group was 257.76 muts/Mb, 74.4 muts/Mb in the mutation of unknown significance group, and 5.81 muts/Mb in the wild type group.The study found significant differences in TMB-H status among the three groups, with all P-values less than 0.01.MSI-H status was detected in 1 case(16.7%, 1/6), 14 cases(77.8%, 14/18), and 18 cases(7.1%, 18/276)in the deleterious mutation group, variant of undetermined significance group, and wild type group, respectively.Notably, patients with variants of undetermined significance had a higher MSI-H status than patients with wild type and POLE deleterious mutations, with all P-values less than 0.01.The frequencies of co-mutations in KRAS, NRAS, BRAF, and PIK3CA were higher in the deleterious mutation group compared to the mutation of undetermined significance group and wild type group(all P<0.05). Conclusions:Colorectal cancer(CRC)patients with harmful mutations and variants of undetermined significance exhibit unique clinicopathological features.Patients with variants of undetermined significance are more likely to develop colon cancer, show poor differentiation, and have higher frequencies of TMB-H(tumor mutational burden)and MSI-H(microsatellite instability-high).
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Objective:To analyze and summarize the clinical characteristics, endoscopic manifestations, pathology and treatment of gastric adenocarcinoma of the fundic gland(GA-FD)to promote clinicians' understanding of this disease.Methods:The clinical data of 3 patients with GA-FD admitted to Beijing Hospital from May 2020 to January 2022 were retrospectively analyzed.Among them, 2 presented with abdominal distension or abdominal pain.The other case was diagnosed during follow-up endoscopy after gastrectomy for gastric cancer.A diagnosis of GA-FD was made based on the results of white light imaging, magnifying endoscopy, pathology and immunohistochemistry.In addition, we reviewed the literature about GA-FD between January 1990 and April 2021 from both national and international reports of 195 cases.We analyzed and summarized the endoscopic and pathological characteristics of the disease and insights on its diagnosis and treatment.Results:Of all 198 cases, patients had a male/female ratio of 1.6/1.0 and an average age of 65.3 years(range: 39-87 years).79.82%(91/114)of the patients were negative for Helicobacter pylori.Gastroscopy showed that the average diameter was 8.97 mm, and 89.9%(178/198)of the patients had lesions infiltrating into the submucosa.91.98%(149/162)of the patients had gastric chief cells as the predominant cell type, 98.86%(130/140)had no lymphovascular invasion, and 97.6%(162/166)had no recurrence or metastasis.Conclusions:GA-FD is a rare gastric cancer, with low-grade atypia and highly differentiated tissues.The mechanisms of GA-FD are not clear and the disease is more commonly seen in the elderly.There is no obvious correlation between Helicobacter pylori infections and GA-FD.Gastric chief cells make up the predominant cell type.The results of endoscopy, pathology and immunohistochemistry can help confirm the diagnosis.The prognosis of most cases is good.
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Objective@#To analyze and investigate the effects of implant location and axial direction on the stress distribution of implants, abutments, central screws, and crowns during immediate loading of maxillary mesial incisors with different alveolar fossa morphology based on three-dimensional finite element method.@*Methods@#Referring to the oral CBCT images of a healthy adult, a three-dimensional finite element model was established for immediate implant loading of maxillary central incisors with three alveolar fossa morphs: labial, intermediate, and palatal; different implant sites(apical site, palatal/labial site) and axes(tooth long axis, alveolar bone long axis) were simulated; the established model was loaded with a force of 100 N. ANSYS software was applied to analyze the stress values of the implants, abutments, central screwss, and crownss. @*Results@#The 3D finite element models of 12 maxillary central incisors with different alveolar sockets were successfully established;the implants and their superstructures were least stressed when the maxillary central incisors with partial labial and partial palatal shape were placed along the long axis of the alveolar bone in the palatal/labial position for immediate implant loading;the implants and their superstructures were least stressed when the maxillary central incisors with central shape were placed along the long axis of the tooth in the palatal position for immediate implant loading. The implant and its superstructure were subjected to the least stress when the implant was placed along the long axis of the tooth in the immediate loading position. @*Conclusion@#The bio-mechanical characteristics of the implant and its superstructure are influenced by the different socket morphology, implantation sites and axes. Therefore, in clinical practice, different implantation axes and implantation sites should be developed for different socket morphs.
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Diabetic retinopathy(DR)is the most prevalent and severe ocular complication in people with diabetes, and it is one of the leading causes of blindness in adults. In recent years, drug therapy represented by anti-vascular endothelial growth factor(VEGF)agents has become the first-line therapy in DR treatment, but it cannot reverse retinal non-perfusion areas, microaneurysms and abnormal teleangiectatic capillaries, those who cannot be treated on time are at risk of disease progression. Laser photocoagulation has been widely applied for more than 40 years, it can effectively reduce the rate of blindness by eliminating the non-perfusion areas of capillaries, and panretinal photocoagulation(PRP)has been the primary treatment for DR. With the continuing innovations in laser technology, on the basis of maintaining the curative effect, the aim of minimizing retinal damage and adverse side effects has been realized. A combination of laser photocoagulation and anti-VEGF agents can achieve complementary advantages and better efficacy. Deepening the clinical research on laser therapy and laser therapy combined with anti-VEGF agents in the treatment of DR may help to establish the personalized treatment corresponds with our national conditions. This article briefly reviews the latest application progress of laser therapy in DR treatment in the era of anti-VEGF agents.
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Objective To investigate the influence of implant location and axial direction on stress distributions at the implant bone interface of maxillary central incisors with different alveolar fossa morphology by immediate implantation under immediate weight-bearing. Methods With reference to dental cone beam computed tomography (CBCT) image data from a healthy adult, the three-dimensional ( 3D) finite element models of maxillary central incisors with three types of alveolar fossa ( buccal, mediate, and palatal type) by immediate implatation under immediate weight-bearing were established. Different implant sites ( apical site, palatal / labial site) and axial directions (long axis of the tooth, long axis of the alveolar bone) were simulated. The established models were subjected to 100 N force at different angles (0°, 30°, 45°, 60°, 90°). The stresses in the alveolar bone around the implant were analyzed by the ANSYS software. Results Twelve 3D finite element models of maxillary central incisors with different alveolar fossa morphology by immediate implantation under immediate weight-bearing were successfully established. When alveolar fossa with buccal and mediate shape was applied with immediate implantation under immediate weight-bearing, it was easier to obtain good biomechanical properties of the implant-bone interface when implants were placed at palatal site along long axis of the alveolar bone. When alveolar fossa with palatal shape was applied with immediate implantation under immediate weight bearing, the equivalent stresses on peri-implant alveolar bone were much smaller than those on apical site, regardless of whether the implant was placed along long axis of the tooth or the long axis of the alveolar bone. Conclusions Different alveolar fossa morphology, implant location and axial direction will affect characteristics of implant-bone interface of maxillary central incisors with immediate implantation under immediateweight-bearing. In clinical practice, surgical planning on different axial direction and location of implantation should be developed for alveolar fossa with different morphology.
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Diabetic macular edema(DME)and age-related macular degeneration(ARMD)are the leading causes of visual impairment and blindness worldwide, and their common pathological features are increased vascular permeability and abnormal neovascularization, in which cytokines such as vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)play an important role. Intravitreal injection of anti-VEGF agents significantly changed the clinical management of DME and ARMD, but limitations such as the non-responsive cases, the treatment burden and risks caused by frequent injections need to be overcome. Faricimab, a novel bispecific monoclonal antibody that simultaneously targets VEGF-A and Ang-2, can effectively reduce vascular permeability, decrease the number of neovascularization and alleviate retinal edema. Registered clinical studies have shown that Faricimab is effective in improving vision and reducing retinal edema, which is non-inferior to Aflibercept and Ranibizumab, maintains a long dosing interval, and has a high safety profile. This article reviews the latest advances in the treatment of DME and ARMD with Faricimab.
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Salvianolic acid B(Sal B) is the main water-soluble component of Salvia miltiorrhiza Bunge. Studies have found that Sal B has a good protective effect on blood vessels. Sal B can protect endothelial cells by anti-oxidative stress, inducing autophagy, inhibiting endoplasmic reticulum stress(ERS), inhibiting endothelial inflammation and adhesion molecule expression, inhibiting endothelial cell permeability, anti-thrombosis, and other ways. In addition, Sal B can alleviate endothelial cell damage caused by high glucose(HG). For vascular smooth muscle cell(VSMC), Sal B can reduce the synthesis and secretion of inflammatory factors by inhibiting cyclooxygenase. It can also play a vasodilatory role by inhibiting Ca~(2+) influx. In addition, Sal B can inhibit VSMC proliferation and migration, thereby alleviating vascular stenosis. Sal B also inhibits lipid deposition in the subendothelium, inhibits macrophage conversion to foam cells, and reduces macrophage apoptosis, thereby reducing the volume of subendothelial lipid plaques. For some atherosclerosis(AS) complications, such as peripheral artery disease(PAD), Sal B can promote angiogenesis, thereby improving ischemia. It should be pointed out that the conclusions obtained from different experiments are not completely consistent, which needs further research. In addition, previous pharmacokinetics showed that Sal B was poorly absorbed by oral administration, and it was unstable in the stomach, with a large first-pass effect in the liver. Sal B had fast distribution and metabolism in vivo and short drug action time. These affect the bioavailability and biological effects of Sal B, and the development of clinically valuable Sal B non-injectable delivery systems remains a great challenge.
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Endothelial Cells , Oxidative Stress , Benzofurans/pharmacology , LipidsABSTRACT
Objective@#To understand the online learning related screen use duration and screen types in school aged children in Shanghai during the COVID-19 epidemic.@*Methods@#Random clustering sampling was used to select 5 591 parents of students from 8 primary and junior schools that are in the sampling pool of the national myopia survey in districts of Jiading, Pudong and Baoshan in Shanghai in April 2020. Electronic questionnaire was administered to parents regarding their child s online learning related screen use.@*Results@#On average, the median weekly duration of online learning related screen use was 13.33 hours, the curricular and extracurricular parts of which were 10(8.75，16.67) and 0(0，3.33) hours, respectively. About 29.44% of investigated school aged children only used small size screen for online learning. Children in higher grades, being myopic and parents neither being myopic were associated with reporting higher weekly duration( P <0.05); children in higher grades of primary school and parents neither being myopic were associated with a higher likelihood of using small size screen for online learning( P <0.05).@*Conclusion@#At the early stage of the COVID-19 epidemic, the burden associated with online learning related screen use was high in school aged children in Shanghai. Health education regarding online learning related screen use should be addressed in parents to guide their children to use screen appropriately.
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The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention, while the differences of protein expression regulated by Jingui and Liuwei remain to be studied. This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days. The protein expression was quantified using LC-MS/MS. The results showed that among the 5 860 proteins tested, 151, 282 and 75 proteins responded to Jingui alone, Liuwei alone, and both drugs, respectively. The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group. The proteins up-regulated by Jingui were mainly involved in membrane transport, synaptic vesicle cycle, serotonergic synapse, dopaminergic synapse and so on, suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system. The proteins down-regulated by Liuwei were mainly involved in membrane transport, synapse, ion transport(potassium and sodium transport), neurotransmitter transport, innate and acquired immune responses, complement activation, inflammatory response, etc. In particular, Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily, which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport. Finally, consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior. This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.
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Animals , Mice , Chromatography, Liquid , Drugs, Chinese Herbal/pharmacology , Hippocampus/metabolism , Proteome/metabolism , Proteomics , Tandem Mass SpectrometryABSTRACT
Diabetic macular edema(DME)has become the leading cause of vision loss in patients with diabetes. Currently, intravitreal injection of anti-vascular endothelial growth factor(VEGF)therapy is the first-line treatment for DME. However, the economic burden and related complications brought by frequent injections should not be ignored. Therefore, the drugs with longer-lasting effects and longer injection intervals must be explored. Brolucizumab is a single-chain antibody fragment(scFv)with a high affinity for VEGF. Compared with other available anti-VEGFs, it has the characteristics of smaller molecular weight, higher tissue permeability and durable therapeutic effect. Clinical studies and real-world evidences showed that Brolucizumab is non-inferior to aflibercept in improving visual acuity in patients with DME. And Brolucizumab is more effective in regressing intra-retinal fluid and reducing central foveal thickness(CSFT)with longer injection interval. At the same time, Brolucizumab has a low incidence of adverse events and favourable safety after intraocular injection. This article reviews the latest progress of Brolucizumab in the treatment of DME.
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This study is to observe whether platycodin D has the guiding role in treatment of mouse lung cancer with doxorubicin and explore its guiding mechanism. In vitro, platycodin D and doxorubicin(alone or in combination) were added into Lewis lung cancer(LLC) cells to detect the cell proliferation and doxorubicin uptake. Cell morphological changes were analyzed by cell holographic analysis system; cell gap junctional intercellular communication(GJIC) was tested by fluorescent yellow tracer; lyso-tracker red was used to examine lysosomal function; LC-3 B(Light chain 3 beta)and P62(heat shock 90-like protein)staining were used to test auto-phagy and autophagic degradation respectively; and P-glycoprotein(P-gp) expression was examined by Western blot. In vivo, lung solid tumor was formed in mouse LLC cells via intravenous injection. Platycodin D and doxorubicin(alone or in combination) were used to treat tumor-bearing mice for four weeks, and then the tumor size was examined, mouse survival time was recorded, doxorubicin uptake in lung tissues was tested, and lung tissues were stained for observation by HE(hematoxylin-eosin) and immunohistochemistry. The results showed that platycodin D at the experimental concentration had no effect on LLC cell proliferation but decreased LLC cell volume, promoted the cells to uptake doxorubicin and enhanced the inhibitory action of doxorubicin on cell proliferation. Platycodin D could promote GJIC and lysosomal function, increase autophagy and autophagic degradation and suppress P-gp expression. Platycodin D at the experimental dose in this study had no effect on LLC lung solid tumors in mice, increased doxorubicin uptake in lung tissues and enhanced the therapeutic efficacy of doxorubicin on lung solid tumors. Platycodin D could improve the extracellular matrix deposition in lung solid tumors, decreased the lung mucin 5 AC secretion and pulmonary vessel permeability. In summary, platycodin D had the guiding role in treating mouse lung cancer with doxorubicin, and its guiding mechanism may be associated with the promotion of cell communication, lysosomal function, and improvement of extracellular environment.
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Animals , Mice , Cell Line, Tumor , Doxorubicin , Lung Neoplasms/drug therapy , Saponins , TriterpenesABSTRACT
Objective:To understand the characteristics and diagnosis and treatment of brucellosis with joint pain as the first clinical manifestation, and summarize the clinical classification of brucellosis complicated with joint pain, so as to provide reference for clinical diagnosis and treatment.Methods:Cases of brucellosis with first symptom of joint pain diagnosed in the 940th Hospital of PLA Joint Logistic Support Force from January 2015 to January 2020 were selected. The main clinical features, laboratory examination, diagnosis and treatment were analyzed.Results:A total of 82 patients with joint pain of the first symptom were selected, including 61 males and 21 females. Joint pain was the main complaint of the patients, 63.4% (52/82) of the patients visited spine surgery department, 17.1% (14/82) visited minimally invasive orthopedics department, 12.2% (10/82) visited rheumatic immunology department, and 7.3% (6/82) visited traditional Chinese medicine department. Brucellosis patients with cervical lesions accounted for 22.0% (18/82), combined with lumbar lesions accounted for 51.2% (42/82). The patients with elevated C-reactive protein accounted for 68.3% (56/82), abnormal liver function accounted for 52.4% (43/82), anti "O" positive accounted for 3.7% (3/82), abnormal autoantibodies accounted for 6.1% (5/82), and human leukocyte antigen-B27 (HLA-B27) positive accounted for 12.2% (10/82). Four patients with HLA-B27 positive had sacroiliac arthritis. All patients were cured after standard and full course therapy.Conclusion:Joint pain may be the first symptom of brucellosis, and the lumbar spine and cervical spine are the most vulnerable parts.
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Objective: To evaluate the prevention and treatment effects of acupuncture-moxibustion for Alzheimer disease (AD) based on various AD mouse models.Methods: Several representative types of mouse models were selected according to the pathophysiological causes of AD, including senescence accelerated mouse/prone (SAMP) mice, soluble amyloid-β protein (Aβ) injection mice/rats, amyloid precursor protein (APP) transgenic mice, and APP/PS1 double transgenic mice. Through the observation of behavioral changes and analysis of core items, the possible mechanisms of acupuncture-moxibustion in preventing and treating AD were explored. Results: Acupuncture-moxibusiton therapy can improve AD mice's cognitive dysfunction; the major action mechanisms including increasing cerebral blood flow, improving the expressions of vital proteins in the hippocampus, preventing neuron cell apoptosis, promoting the clearance of Aβ deposition, activating autophagy pathway to reduce memory deficits and regulating the metabolisms of brain-derived neurotrophic factor, tyrosine kinase receptor B, N- acetylaspartate and glutamic acid. Conclusion: Although the optimal mouse model is not determined, it is sure that acupuncture-moxibustion therapy can improve cognitive function. A more suitable AD animal model should be duplicated in order to better explore the inherent action mechanism of acupuncture-moxibustion in preventing and treating AD.
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Objective:To investigate clinical features, diagnosis and treatment of angioimmunoblastic T-cell lymphoma(AITL)in middle and old age patients.Methods:This was a retrospective study.A total of 33 middle-aged and elderly patients(a median age of 64 years, range 47~85 years)with AITL admitted to our hospital from May 2008 to March 2017, including 54.5% male(18 cases), were enrolled in this study.Clinical manifestations, pathology, imaging and survival data of patients were collected.The objective response rate(ORR)of patients with different therapeutic regimens was analyzed.The survival analysis was conducted by using the Kaplan-Meier method, the survival rate was analyzed by using the Log-rank method, and multivariate analysis was conducted by using the proportional hazards regression model.Results:The median overall survival(OS)was 26.0 months(8.5-43.5 months). The 1-year, 3-year and 5-year OS rate was 66.7%(22 cases), 45.5%(15 cases)and 24.2%(8 cases), respectively.The ORR of first-line chemotherapy with CHOP-like regimens(cyclophosphamide, doxorubicin, vincristine, prednisone)was 65.5%(19/29)and the incidence of serious adverse reactions was 64.5%(20/31). Single-factor chi-square testing showed that age ≥60 years, Barthel score ≥90, Eastern Cooperative Oncology Group performance status score(ECOG-PS)≥2, anemia, International prognostic index(IPI)score of 4~5, receiving chidamide treatment were influncing factors for the prognosis in middle-aged and elderly patients with AITL( χ2=5.103, 4.306, 6.004, 4.030, 6.348 and 4.080, P<0.05). Cox multivariate analysis showed that age ≥60 years and receiving chidamide treatment were independent prognostic factors affecting the 5-year survival rate of middle-aged and elderly AITL patients( OR=0.313 and 4.964, P<0.05). That the OS was better in the group receiving chidamide treatment than in the group without chidamide treatment( P<0.05). Conclusions:Clinical features of AITL are diverse and lack of specificity.Most patients present with advanced stage AITL at the initial diagnosis.The 5-year OS rate is low.AITL patients aged over 60 years have a poor prognosis.Chidamide can improve the OS rate.
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Intracorporeal classic gastrointestinal anastomosis using circular stapler in totally laparoscopic gastrectomy (TLG) for gastric cancer requires intracorporeal anvil placement and suitable access for introduction of the circular stapler to the abdominal cavity without gas leak. The novel techniques for anvil placement have been updated, but there is no progress for proper access for circular stapler. In the study, intracorporeal circular-stapled gastrointestinal anastomosis were successfully accomplished using a novel device of sealed cap access with a central hole (WLB-60/70-60/100, Wuhan Widerep Medical Instrument Co.,Ltd, China) customized to the incision protection retractor for the simple and accessible introduction of the circular stapler and anvil under the optimal maintenance of pneumoperitoneum pressure in TLG. In these 3 cases, there was no gas leakage and the pneumoperitoneum was well maintained when performing the gastrointestinal anastomosis, and there was no transition to laparotomy or other anastomosis techniques. The result suggests that the sealed cap access could be a novel choice for introduction of the circular stapler to the abdominal cavity in order to obtain laparoscopic circular-stapled gastroin-testinal anastomosis in TLG.
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Humans , Anastomosis, Surgical , China , Gastrectomy , Laparoscopy , Stomach Neoplasms/surgery , Surgical StaplingABSTRACT
Objective@#The research was aimed to discuss the role of science and technology research in the public health emergency response, and to provide theoretical support for building Healthy China, implementing the National Strategy of Innovation-Driven Development.@*Methods@#Take COVID-19 as an example, to sum up the characteristics and the function of science and technology research in the public health emergency prevention and control system.@*Results@#In order to make the scientific and technological research as the supporting system in public health emergency, we need to strengthen the basic research, to improve the research and development for controlling product with the independent intellectual property, to optimize the training system and evaluating system in public health technology, to deepen the international collaboration and to popularize the basic scientific knowledge.@*Conclusions@#Through systematically arrangement for disease controlling and prevention, for the industrial supporting, for the health improvement, for the talent training system and for the cooperation and the communication, we need to fasten the technological innovation for better preparation and responding to public health emergencies.
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Objective@#To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2 (LMP2) modified dendritic cells (DCs) that boosts specific responses of cytotoxic T lymphocytes (CTLs) to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma (NPC).@*Methods@#DCs were derived from peripheral blood monocytes of patients with NPC. We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2 (rAd-LMP2). NPC patients were immunized with 2 × 10 @*Results@#We demonstrated that DCs derived from monocytes displayed typical DC morphologies; the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay. Twenty-nine patients with NPC were enrolled in this clinical trial. The LMP2-DCs vaccine was well tolerated in all of the patients. Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC. The follow-up data of 29 immunized patients from April, 2010 to April 2015 indicated a five-year survival rate of 94.4% in responders and 45.5% in non-responders.@*Conclusion@#In this pilot study, we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC. Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC, which warrants further clinical testing.
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Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Cancer Vaccines/therapeutic use , China , Dendritic Cells/immunology , Immunotherapy/methods , Injections, Intradermal , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Neoplasms/therapy , T-Lymphocytes, Cytotoxic/immunology , Viral Matrix Proteins/therapeutic useABSTRACT
Objective: To identify the anti-depressive effect of ferulic acid (FA) in mice exposed to lipopolysaccharide (LPS) and explore its molecular mechanisms. Methods: The mice were divided into 5 groups as follows: Control, LPS, LPS + SP, LPS + FA, and LPS + FA + anisomycin. The LPS + FA and LPS + FA + anisomycin groups were administered with FA (100 mg/kg, i.p.) once daily continuously for 7 days, and the other groups received an equivalent volume of saline. On the 7th day, LPS (0.1 mg/mL, i.p.) was injected in all mice except the control group 30 min after FA or saline administration. The LPS + SP and LPS + FA + anisomycin groups were intravenously administered with SP600125 [c-Jun N-terminal kinase (JNK) inhibitor] (100 μL/site, i.v.) and anisomycin (JNK activator) (100 μL/site, i.v.) 15 min before LPS, respectively. The depressive behaviors were assessed by open field test, sucrose preference test, and forced swimming test at 24 h post-LPS administration. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels in plasma were measured by ELISA. The levels of phospho-JNK, TNF-α, IL-1β, Bcl-2, Bax, cytochrome c and caspase-3 were evaluated by Western blotting. Results: FA alleviated depression symptoms caused by LPS in mice, including increasing sucrose water consumption in sucrose preference test and reducing the immobility time in forced swimming test. FA could inhibit upregulated levels of phospho-JNK, TNF-α, and IL-1β. FA also markedly decreased Bax, caspase-3, and cytochrome c, and increased Bcl-2 levels. Besides, SP600125 showed neuroprotective effect similar to FA which was attenuated by anisomycin. Conclusions: FA attenuates inflammation and apoptosis by inhibiting LPS-induced activation of JNK to alleviate depression-like behaviors.
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Objective:The research was aimed to discuss the role of science and technology research in the public health emergency response, and to provide theoretical support for building Healthy China, implementing the National Strategy of Innovation-Driven Development.Methods:Take COVID-19 as an example, to sum up the characteristics and the function of science and technology research in the public health emergency prevention and control system.Results:In order to make the scientific and technological research as the supporting system in public health emergency, we need to strengthen the basic research, to improve the research and development for controlling product with the independent intellectual property, to optimize the training system and evaluating system in public health technology, to deepen the international collaboration and to popularize the basic scientific knowledge.Conclusions:Through systematically arrangement for disease controlling and prevention, for the industrial supporting, for the health improvement, for the talent training system and for the cooperation and the communication, we need to fasten the technological innovation for better preparation and responding to public health emergencies.
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Objective:To investigate the influencing factors for the recurrence of TNM(T3~4N0M0)stage Ⅱ colorectal cancer in patients aged 75 years and over after radical resection.Methods:Clinicopathologic data of 161 colorectal cancer patients aged 75 years and over undergone radical resection in our hospital from January 2012 to August 2017 were retrospectively analyzed.They were followed up for 49 months(range: 2-84 months). Survival analysis was conducted by the Kaplan-Meier method and the survival rate was examined using the Log-rank method.Multivariate analysis was conducted by the proportional hazards regression model.Results:Univariate analysis showed that age≥80 years, preoperative comorbidities involving more than 1 system, weight loss≥10%, preoperative intestinal obstruction or perforation, preoperative CEA elevation, preoperative CA199 elevation, depth of primary tumor invasion T4, dissection of lymph nodes<12, vascular invasion, nerve invasion, deficient mismatch repair(dMMR), risk stratification and adjuvant chemotherapy were related factors for the prognosis in patients with TNM stage Ⅱ colorectal cancer aged 75 years and over after radical resection.Multivariate analysis showed that preoperative comorbidities involving more than 1 system, weight loss≥10%, preoperative intestinal obstruction or perforation, preoperative CEA elevation, depth of primary tumor invasion T4, dissection of lymph nodes<12 and vascular invasion were independent risk factors for poor prognosis, and adjuvant chemotherapy was an independent factor for favorable prognosis.The 5-year-disease-free survival(DFS)rate was 41.6% in all patients.The Kaplan-Meier curves indicated that disease-free survival(DFS)between the low-risk, middle-risk and high-risk groups had a statistically significant difference( χ2=14.632, P=0.001). Kaplan-Meier survival analysis showed that high-risk patients receiving Oxaliplatin combined with Capecitabine adjuvant chemotherapy had better DFS than those receiving Capecitabine or non-adjuvant chemotherapy( χ2=11.157, P=0.004). Conclusions:DFS is improved in strictly selected patients with stage Ⅱ colorectal cancer aged 75 years and over and at high risk who receive Oxaliplatin combined with Capecitabine adjuvant chemotherapy.