摘要
The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.
摘要
The cultivation of medical humanistic quality is indispensable in the standardized training of pediatric residents, and it is urgent to explore new educational methods to improve their medical humanistic quality level. In this study, 60 standardized pediatricians participated in the standardized training, 36 in the experimental group received innovative interactive medical humanities education, while 24 in the control group were set up to receive traditional medical humanities education. Short-term and long-term test scores were conducted by questionnaire at the beginning of the standardized training and 2 years later. The results showed that there was no significant difference between the experimental group and the control group in the self-scores of professional quality, moral cultivation, communication skills, legal knowledge and innovative spirit (P>0.05) , but the scores of teaching teachers were improved except innovative spirit (P<0.05) . In addition, compared with the control group, the number of pediatricians with professional honor increased, the doctor-patient communication ability improved, the medical disputes reduced, and the family satisfaction improved in experimental group were increased (P<0.05) . These results indicated that innovative interactive medical humanistic education is an effective method to improve the medical humanistic quality of pediatric residents in standardized training.
摘要
BACKGROUND:Tauroursodeoxycholic acid is a hydrophilic bile acid derivative that has neuroprotective effects in a variety of neurological disease models.However,there are few reports on the effects of tauroursodeoxycholic acid on spinal cord injury. OBJECTIVE:To investigate the effect of tauroursodeoxycholic acid on apoptosis of spinal cord neurons under hypoglycemic and hypoxic conditions,as well as the effect on recovery of motor function in mice after spinal cord injury. METHODS:(1)In vitro experiment:Primary spinal cord neurons were isolated from C57 BL/6 mouse embryos at 13.5 days of gestation.After 72 hours of culture,the cells were divided into three groups.In the normal group,cells were cultured in Neurobasal complete medium that was incubated in a CO2 incubator(5%CO2 + 95%air)for 24 hours.In the oxyglucose-deprived group,sugar-free Neurobasal medium was added and incubated in a triple-gas incubator(94%N2+5%CO2+1%O2)for 12 hours,and then the medium was replaced with Neurobasal complete medium and incubated in a CO2 incubator for 12 hours.In the experimental group,the treatment procedure was approximately the same as that in the oxyglucose-deprived group,except that taurodeoxycholic acid was added along with the sugar-free Neurobasal medium.TUNEL staining was used to detect apoptosis,cell counting kit-8 assay was applied to detect cell activity,and immunofluorescence staining was performed to detect cellular β-microtubule protein expression.(2)Animal experiment:Sixty C57 BL/6 mice were randomly divided into sham-operated group,spinal cord injury group and experimental group,with 20 mice in each group.Animal models of T9-T10 spinal cord injury were established using Allen's percussion method in the spinal cord injury group and the experimental group.Starting from the 1st day after modeling,taurodeoxycholic acid solution was given by gavage in the experimental group and normal saline was given by gavage in the sham-operated and spinal cord injury groups once a day for 14 consecutive days.Spinal cord tissue repair was assessed using behavioral and histological methods. RESULTS AND CONCLUSION:In vitro experiment:TUNEL staining,cell counting kit-8 and immunofluorescence staining showed that compared with the normal group,the number of apoptotic cells was higher(P＜0.01),while cell activity and β-microtubule protein expression were lower in the oxyglucose-deprived group(P＜0.01);compared with the oxyglucose-deprived group,the number of apoptotic cells was lower(P＜0.01),while cell activity and β-microtubule protein expression were higher in the experimental group(P＜0.01).Animal experiment:The Basso-Beattie-Bresnahan scores in the open field test and hind limb footprint experiments showed that the mice in the experimental group had better recovery of walking and motor functions than those in the spinal cord injury group.Hematoxylin-eosin staining showed that significant deformities and cavities were observed at the site of spinal cord injury and the number of nerve cells was significantly reduced in the spinal cord injury group.Compared with the spinal cord injury group,the experimental group showed a significant reduction in the area of spinal cord injury,less spinal cord deformity,fewer cavities,and an increase in the number of nerve cells.Immunofluorescence staining showed that the number of neuronal nucleus-labeled neuronal cells in the spinal cord injury group was less than that in the sham-operated group(P＜0.01),and the number of neuronal nucleus-labeled neuronal cells in the experimental group was higher than that in the spinal cord injury group(P＜0.01).To conclude,tauroursodeoxycholic acid could effectively reduce glucose/oxygen deprivation-induced apoptosis of spinal cord neurons and axonal loss,and promote the recovery of motor function in mice with spinal cord injury.
摘要
Postoperative radiotherapy increase the overall survival rate offor breast cancer improves overall survivalpatients, but. Nevertheless, the heart is at risk of radioactive heart damageradiation-induced cardiac injury due to its anatomical location, which is inevitably exposed to radiation during radiotherapy. The heart is considered a "high-risk organ" sensitive to radiation, and its radiation dose should be as low as possible. Previous studies have evaluated the effect of overall heart radiation dose on long-term cardiovascular events, but the. However, new study has found that the average heart dose does not accurately reflect the degree of heart radiation exposure. In recent years, more and morewidespread attention has been paid to subclinical cardiac injury after radiotherapy, aiming at early identification of latent cardiac injury. In addition, the relationship between specific cardiac substructural doses and arrhythmias is unclear. This paper focuses onIn this article, the limitations of average cardiac dose in predicting radioactive heart injuryradiation- induced cardiac injury, the indicators of early identification of the indicators for cardiac injury and the influencing factors of radiation-induced cardiac injury in breast cancer radioactive heart injurywere illustrated, and focuses on the relationship between radiation damage of different cardiac substructures and arrhythmia was evaluated, so asaiming to achieve fine cardiac risk management in breast cancer patients and reduce the non-cancer mortality in breast cancer patients.
摘要
Objective:To examine the impact of pressure support ventilation(PSV)in combination with low inspired oxygen concentration on atelectasis during the emergence from general anesthesia in elderly patients undergoing robotic-assisted radical prostatectomy.Methods:In this prospective randomized controlled study, a total of 144 elderly patients, aged 65-80 years(average age: 71.4±4.4 years), who were undergoing elective robotic-assisted radical prostatectomy under general anesthesia, were divided into 4 groups(n=36 each)using the random number table method.The groups were as follows: PSV+ 40% fraction of inspiration oxygen(FiO 2)(P40 group), PSV+ 80%FiO 2(P80 group), spontaneous breathing+ 40%FiO 2(S40 group), and spontaneous breathing+ 80%FiO 2(S80 group). These methods were used during the general anesthetic emergence, which refers to the period from the end of the operation to extubation.Atelectasis aeration loss score was measured using ultrasound, and the oxygenation index(OI)was calculated through arterial blood gas analysis.These measurements were recorded at different time points: at the end of surgery(T 1), after extubation(T 2), 30 minutes after entering the post anesthesia care unit(PACU)(T 3), and 48 hours after surgery(T 4). The number of hypoxemia cases(defined as saturation of pulse oxygen <92%)during emergence and within 30 minutes of entering the PACU, as well as the incidence of postoperative pulmonary complications(PPCs)at T 4, were also recorded. Results:A total of 137 patients completed the study.Compared with the P40 group, the patients in the P80 group had higher atelectasis aeration loss scores at T 2[6.0(3.0)scores vs.4.0(2.0)scores; Z=-3.733, P<0.001], the S40 group[8.0(3.0)scores vs.4.0(2.0)scores; Z=-4.868, P<0.001], and the S80 group[9.0(3.0)scores vs.4.0(2.0)scores; Z=-6.835, P<0.001]. At T 3, the S40 group[7.0(2.0)scores vs.5.0(2.0)scores; Z=-4.631, P<0.001]and the S80 group[9.0(2.5)scores vs.5.0(2.0)scores; Z=-6.590, P<0.001]also had higher atelectasis aeration loss scores.There was no significant difference in the incidence of hypoxemia between the four groups during the recovery period( χ2=0.405, P=0.939)and in PACU( χ2=4.048, P=0.256). The incidence of PPCs in the four groups at 48 hours after operation was 5.9%(2/34), 11.4%(4/35), 8.6%(3/35), and 6.1%(2/33)respectively( χ2=0.947, P=0.814). Conclusions:The combination of positive end-expiratory pressure support ventilation(PSV)and low inspired oxygen concentration can effectively decrease the occurrence of atelectasis in elderly patients undergoing robotic-assisted radical prostatectomy during the emergence phase.This approach also helps in reducing the incidence of hypoxemia in the post-anesthesia care unit(PACU)and improves the postoperative oxygenation index.
摘要
Objective An exploration of the molecular mechanism of microRNA-146a(miR-146)inter-vention in Sepsis-induced cardiomyopathy(SIC)using P38MAPK/NF-κB.Methods SD rats were divided into four groups by the random number table method:the normal control group,the SIC model group,the miR-146a agonist group,and the miR-146a inhibitor group.Rats in the normal control group and SIC model group were injected intraperitoneally with 0.2 μL/g saline,rats in the miR-146a agonist group were injected intraperitoneally with 0.2 μL/g miR-146a agonist,rats in the miR-146a inhibitor group were injected intraperitoneally with 0.2 μL/g miR-146a inhibitor;24 h later,rats in the SIC model group,miR-146a agonist group,and miR-146a inhibitor group were injected intraperitoneally with lipopolysaccharide(LPS)to prepare the SIC rat model,and the normal control group was injected with an equal amount of saline.Histopathological morphology was observed by HE staining;apoptosis rate of cardiomyocytes was detected by TUNEL;cardiac troponin I(cTnI)and B-type brain natriuretic peptide(BNP)contents were detected by ELISA;creatine kinase cardiac muscle binding(CK-MB)and myoglobin(Mb)contents were detected by chemiluminescence;p38 mitogen activation in rat myocardial tissue was detected by Western blot protein kinase(p38MAPK),nuclear factor-kB(NF-κB),tumor necrosis factor-α(TNF-α)and intercellular adhesion molecule-1(ICAM-1)by Western-Blot;miR-146a,TNF-α,interleukin-1α(IL-1α)and interleukin-1β(IL-1β)mRNA by reverse transcription quantitative(RT-q)PCR.Results Myocardial cells in the normal control group were uniform in size,neatly arranged,with distinct transverse lines,and had normal structure;myocardial cells in the SIC model group and miR-146a inhibitor group were disordered,with myocardial fibers fragmented and expanded at intervals.Myocardial structural damage was minimized in the miR-146a agonist group compared to the SIC model group.Compared with the normal control group,the apoptosis rate,serum cTnI,BNP,CK-MB,Mb levels,myocardial tissue p-p38 MAPK,p-NF-κB p65,TNF-α,ICAM-1 protein expression levels,TNF-α,IL-1α,miR-146a mRNA levels were significantly higher in the SIC model group,miR-146a agonist group and miR-146a inhibitor group,IL-1β mRNA levels were significantly increased and miR-146a mRNA levels were decreased.Compared with the SIC model group,the apoptosis rate,serum cTnI,BNP,CK-MB,Mb levels,myocardial tissue p-p38 MAPK,p-NF-κB p65,TNF-α,ICAM-1 protein expression in the miR-146a agonist group of rats levels,TNF-α,IL-1α,IL-1β mRNA levels were significantly reduced,and miR-146a mRNA levels were increased.Conclusion miR-146a has the ability to modulate the p38 MAPK/NF-κB signaling axis and the release of inflammatory factors.High miR-146a expression has some negative influence on the inflammatory response,reducing the onset and development of the inflammatory response while improving it.It can offer SIC early interven-tion therapy with a pre-study mechanism and theoretical support.
摘要
Objective:To investigate the collection efficiency of peripheral blood hematopoietic stem cells and explore its influencing factors.Method:The parameters of the collection process, blood routine indexes and the number of MNC and CD 34+ cells of the product were detected by Fresenius blood cell separator, Mindray blood cell analyzer and BD flow cytometer. A retrospective analysis was performed on 72 patients who underwent autologous peripheral blood hematopoietic stem cell transplantation in Southwest Hospital of Army Medical University from January 2013 to January 2021, including the correlation among gender, age, blood routine indexes, collection circulation volume and MNC and CD 34+ cell count in these cases, and influence of various factors on collection efficiency of peripheral blood stem cells. The correlation among gender, age, blood routine indexes, collection circulation volume and MNC and CD 34+ cell count in 72 cases of autologous transplantation patients, and influence of various factors on collection efficiency of peripheral blood stem cells were analyzed retrospectively. Results:There were no significant differences in collecting efficiency of peripheral blood stem cells among patients with different age, sex and disease type ( P>0.05). The collected MNC count of all patients was positively correlated with the collection cycle count ( r = 0.33, P<0.001) and WBC count after mobilization ( r = 0.41, P<0.001). The number of CD 34+ cells collected was positively correlated with MNC count after mobilization ( r = 0.38, P<0.001) and the amount of white membrane collected ( r = 0.48, P<0.001). Logistic multivariate regression analysis showed that MNC count after mobilization: P<0.001, 95% CI 0.07(0.05 - 0.09), collection cycle amount [ P<0.001, 95% CI 0.00(0.00 - 0.00)] and postharvest total amount [ P<0.001, 95% CI 0.07(0.05 - 0.10)] were the influencing factors of the collected MNC number. Meanwhile, these factorswere also the influencing factors of the collected CD 34+ number (MNC count after mobilization: P<0.001, 95% CI 0.09(0.04 - 0.14); collection cycle amount: P = 0.003, 95% CI 0.00(0.00 - 0.00); postharvest total amount: P = 0.005, 95% CI 0.08(0.03 - 0.14)). Conclusions:The collection efficiency of peripheral blood stem cells varies greatly among individuals. The more MNC counts after mobilization, the more peripheral blood stem cells could be collected. In order to obtain high collection efficiency, it is necessary to adjust the parameters of peripheral blood MNC before collection, and pay attention to the collection circulation quantity, postharvest total amount and white membrane volume.
摘要
Whole breast radiotherapy after breast-conserving surgery for early-stage breast cancer increases local control rate and reduces postoperative recurrence. Compared to supine position, whole breast radiation therapy in the prone position provides dosimetric advantages and cosmetic outcomes in patients with large breasts. With the development of various radiotherapy techniques and tools, the radiation volume and dose for target and organs at risk (such as heart and lung) have changed. Models for the prediction of preferable treatment position in breast radiotherapy without the need for CT simulation and plan evaluation in both positions have been developed and implemented in radiotherapy practice. This paper briefly reviews the progression in the techniques and dosimetry of whole breast radiotherapy in prone position after breast-conserving surgery for early breast cancer.
摘要
@#Objective To investigate the effects of mercury on T lymphocytes and serum immune indexes of workers with Methods occupational mercury exposure. A total of 45 workers with occupational mercury exposure were selected as the ， mercury exposure group and 47 workers without occupational mercury exposure were selected as the control group using the judgment sampling method. Cold atomic absorption spectrometry was used to detect the urinary mercury level of the two groups. （ ） +， + +， + + - + Flow cytometry was used to detect the proportion of cluster of differentiation CD 3 CD3CD4 CD3CD8 and CD3CD19 ， - （ - ） - （ - ） cells in peripheral blood and the levels of tumor necrosis factor α TNF α and interleukin 8 IL 8 in serum. The levels of （ ） ， Results immunoglobulin Ig A IgG and IgM in serum were measured by immune nephelometry. The urinary mercury level of （ ： vs ，P ） individuals in the mercury exposed group was higher than that of the control group median 92.7 13.2 μg/g Cr <0.01 . The +， + +， - + proportion of CD3 CD3CD4 CD3CD19 cells in peripheral blood and serum IgG level in the mercury exposed group （ P ）， - - （ P ） decreased all <0.05 and the serum TNF α and IL 8 levels increased all <0.01 compared with the control group. Urinary - + mercury level was negatively correlated with the proportion of CD3CD19 cells in peripheral blood and serum IgG level in the ［ （r） ， ， P ］， study subjects Spearman correlation coefficient S were −0.21 and −0.31 respectively all <0.05 and positively - - （r ， ， P ） ， correlated with serum TNF α and IL 8 levels S were 0.36 and 0.39 respectively all <0.05 . However the urinary mercury （ P ）， +， + +， level was neither correlated with IgA and IgM levels in serum all >0.05 nor with the proportion of CD3 CD3CD4 + + （ P ） Conclusion CD3CD8 cells in peripheral blood all >0.05 . Occupational exposure to mercury can lead to abnormal ， changes in peripheral blood T lymphocyte subsets B lymphocytes and serum immune factors in workers. The mercury load of occupational mercury exposure workers may impact their immune function.
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Different from other trauma, the scar and pigmentation formed after healing of burn wound not only hinder beauty but also easily lead to a series of sequential psychological problems, such as depression and anxiety. Music therapy, as a supplementary treatment, is widely used in many fields including medical and health care and psychological regulation. However, affected by factors such as medical resources, the awareness and acceptance of music therapy among burn treatment workers in China are still low. Based on the clinical characteristics of burns, this paper matches the applicability of music therapy with it, summarizes the supplementary application of music therapy in the field of burn treatment, expounds this natural science with both science and aesthetics, and puts forward feasible suggestions for its future development.
Subject(s)
Humans , Anxiety , Burns/therapy , Cicatrix , Music Therapy , Wound Healing摘要
Vitamin D plays an important role in mineral and bone homeostasis, immune responses, cardiovascular function and keratinocyte proliferation and differentiation. Vitamin D performs most of its functions by binding to vitamin D receptors (VDR), which interact with other intracellular signaling pathways to regulate bone metabolism, inflammation, immunity, cell cycle progression and apoptosis. Autophagy is a basic stress response in yeast, plants and mammals, and plays a critical role in maintaining optimal functional states at the level of cells and organs. Vitamin D/VDR plays an anti-infection role via inducing and regulating autophagy.
Subject(s)
Animals , Humans , Autophagy , Inflammation , Mammals/metabolism , Receptors, Calcitriol/metabolism , Vitamin D/physiology , Vitamins摘要
The cultivation of medical humanistic quality is indispensable in the standardized training of pediatric residents, and it is urgent to explore new educational methods to improve their medical humanistic quality level. In this study, 60 standardized pediatricians participated in the standardized training, 36 in the experimental group received innovative interactive medical humanities education, while 24 in the control group were set up to receive traditional medical humanities education. Short-term and long-term test scores were conducted by questionnaire at the beginning of the standardized training and 2 years later. The results showed that there was no significant difference between the experimental group and the control group in the self-scores of professional quality, moral cultivation, communication skills, legal knowledge and innovative spirit (P>0.05) , but the scores of teaching teachers were improved except innovative spirit (P<0.05) . In addition, compared with the control group, the number of pediatricians with professional honor increased, the doctor-patient communication ability improved, the medical disputes reduced, and the family satisfaction improved in experimental group were increased (P<0.05) . These results indicated that innovative interactive medical humanistic education is an effective method to improve the medical humanistic quality of pediatric residents in standardized training.
摘要
Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on perioperative anxiety and postoperative pain in living kidney donors (LKDs).Methods:Seventy-two American Society of Anesthesiologists physical status Ⅰ or Ⅱ LKDs, aged 18-64 yr, with body mass index of 18-28 kg/m 2, undergoing living kidney transplantation, were selected, and divided into 2 groups ( n=36 each) using a random number table method: TEAS group (group T) and sham stimulation group (group S). In group T, TEAS was performed on the forenoon at 1 day before surgery (T 0), at 30 min before anesthesia induction on the morning of the operation day (T 1) and on the forenoon at 1 day after surgery (T 2) at bilateral Neiguan, Taichong and Yintang with a frequency 2-100 Hz, disperse-dense waves and current intensity 6-15 mA, and each TEAS lasted for 30 min.Only electrode patches were applied at the same acupoint and at the same time point, but no stimulation was applied in group S. In T and S groups, brachial venous blood samples were collected before each stimulation for measurement of the plasma 5-hydroxytryptamine (5-HT) concentration.The Hospital Anxiety Depression Scale-Anxiety subscale (HADS-A) scores at T 0, T 1, T 2, on day 3 after surgery (T 3) and before discharge (T 4) in the 2 groups were recorded.The consumption of anesthetics during operation, laryngeal mask airway removal time, requirement for rescue analgesia within 72 h after surgery and the development of postoperative complications were recorded.The LKDs were followed up by telephone at 3 months after surgery (T 5) to record the scores of HADS-A and Leeds Assessment of Neuropathic Symptoms and Sign (LANSS) scale. Results:Compared to group S, the incidence of anxiety was significantly decreased T 1, T 2 and T 3, the incidence of rescue analgesia within 72 h after surgery was decreased, plasma concentration of 5-HT was increased at T 1 and T 2, the incidence of postoperative nausea and vomiting was decreased, and the time to first flatus was shortened in group T ( P<0.05). There was no significant difference in the consumption of anesthetics during operation, laryngeal mask airway removal time, and the incidence of anxiety and neuropathic pain within 3 months after surgery between the 2 groups ( P>0.05). Conclusion:TEAS can relieve early preoperative and postoperative anxiety and alleviate postoperative pain in LKDs.
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Objective:To investigate the effect of fibrinogenase combined with aspirin on blood viscosity and clinical efficacy in patients with acute cerebral infarction.Methods:Senventy patients with mild to moderate acute cerebral infarction from October 2016 to June 2020 were collected from the Third People′s Hospital of Dalian. Patients were divided into control group and treatment group according to the random number table method, with 35 cases in each group. The control group was given oral aspirin plus an intravenous drip of normal saline equal to the treatment group, while the treatment group was given aspirin plus fibrinogenase by intravenous drip. Both groups were given symptomatic treatment such as management of blood glucose, blood pressure, arteriosclerosis plaque stabilization and improvement of circulation for 10 d. Blood viscosity and neurological deficit score were measured before and after treatment.Results:Compared with baseline values, WBV showed a slight decrease in all shear rates in the control group after treatment compared with that before treatment, but the difference was not statistically significant ( P>0.05). In the treatment group, all shear rates decreased compared with that before treatment ( P<0.05), and the effect of WBV was significant compared with that of the control group ( P<0.05). The improvement of neurological function in the treatment group was better than that in the control group. The significant efficiency and the total effective rate in the treatment group were significantly higher than those in the control group: 34.3% (12/35) vs. 25.7% (9/35), 88.6% (31/35) vs.71.4% (25/35). Conclusions:Fibrinogenase combined with aspirin in the treatment of acute cerebral infarction patients can safely and effectively reduce blood viscosity and improve clinical symptoms.
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OBJECTIVE@#To investigate the effect of lysosomal-associated protein transmembrane-4 Beta(Laptm4b) deletion on hematopoietic stem/progenitor cells (HSPCs) homeostasis in mice.@*METHODS@#The hematopoietic system specific Laptm4b-deficient mice were constructed. The number and proportion of HSPCs (LSK, LT, ST, MPP, etc) in Laptm4b-deficient mice were analyzed by flow cytometry. Single SLAM-HSC cell was sorted by flow sorter and cultured in vitro to measure the effect of Laptm4b deletion on the colony forming ability of hematopoietic stem cells (HSCs). The effect of Laptm4b-deficient on the reconstitution ability of HSCs in mice was detected by competitive transplantation experiment of SLAM-HSC cells.@*RESULTS@#Laptm4b deficiency could moderately upregulate the proportion of T cells in the peripheral blood of the mice, but showed no significant effect on the proportion and number of HSPCs. Laptm4b deletion showed no effect on the reconstruction ability of HSCs after competitive transplantation, but it could inhibit the colony formation of HSCs in vitro.@*CONCLUSION@#LAPTM4B may play a role in HSCs under the proliferation stress. Laptm4b-deficient in mice hematopoietic system showed no significant effect on the HSPCs homeostasis maintenance and reconstruction ability.
Subject(s)
Animals , Mice , Cell Proliferation , Flow Cytometry , Hematopoietic Stem Cells , Homeostasis , Transcription Factors摘要
In spite of no homology in sequences‚ Vip3A and Cry1Ia toxins of Bacillus thuringiensis (Bt) share common characteristics‚ such as translocation across cell membranes after synthesis at the early stage of sporulation. The aim of the present study was to compare the regulation patterns and activities of the promoters of vip3A (P
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BACKGROUND@#Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Large tumor suppressor 1 (LATS1) and large tumor suppressor 2 (LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether Lats1 and Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice.@*METHODS@#Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of Lats1 and Lats2 in subsets of progenitor cells and mature bone marrow cells. A clustered regularly interspaced short palindromic repeats system was used to generate Lats1 or Lats2 knockout mice. Complete blood cell counts were used to compare the absolute number of white blood cells, lymphocytes, monocytes, neutrophils, and platelets between Lats1 or Lats2 heterozygotes and littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in Lats1 or Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student's t test.@*RESULTS@#Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. Lats1 or Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in Lats1 (HPC: wild-type [WT] vs. heterozygote, 220,426.77 ± 54,384.796 vs. 221,149.4 ± 42,688.29, P = 0.988; HSC: WT vs. heterozygote, 2498.932 ± 347.856 vs. 3249.763 ± 370.412, P = 0.105) or Lats2 (HPC: WT vs. heterozygote, 425,540.52 ± 99,721.86 vs. 467,127.8 ± 89,574.48, P = 0.527; HSC: WT vs. heterozygote, 4760.545 ± 1518.01 vs. 5327.437 ± 873.297, P = 0.502) heterozygotes were not impaired. Moreover, the depletion of Lats1 or Lats2 did not affect the overall survival of the heterozygotes (Lats1: P = 0.654; Lats2: P = 0.152).@*CONCLUSION@#These results indicate that a single allele of Lats1 or Lats2 may be sufficient for normal hematopoiesis.
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BACKGROUND@#Zinc finger and BTB domain-containing protein 46 (Zbtb46) is a transcription factor identified in classical dendritic cells, and maintains dendritic cell quiescence in a steady state. Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia (AML). We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells (HSPCs) compared to mature cells, and higher in AML cells compared to normal bone marrow (BM) cells. However, the role of Zbtb46 in HSPCs and AML cells remains unclear. Therefore, we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells.@*METHODS@#We generated Zbtb46 and Zbtb46Mx1-Cre mice. The deletion of Zbtb46 in Zbtb46Mx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46 and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry.@*RESULTS@#The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46 littermates (Zbtb46vs. Zbtb46 cKO, HPC: 801,310 ± 84,282 vs. 907,202 ± 97,403, t = 0.82, P = 0.46; LSK: 86,895 ± 7802 vs. 102,210 ± 5025, t = 1.65, P = 0.17; HSC: 19,753 ± 3116 vs. 17,608 ± 3508, t = 0.46, P = 0.67). The repopulation ability of HSCs from Zbtb46Mx1-Cre mice was similar to those from Zbtb46 control (P = 0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation.@*CONCLUSION@#Collectively, our data indicate that Zbtb46 is essential for survival and proliferation of AML cells, but dispensable for normal hematopoiesis.
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Atherosclerosis is one of the causes of many cardiovascular diseases. Lipid metabolism disorder is an important risk factor for atherosclerosis. Lipase-targeted screening may help discovery of hypolipidemic and anti-atherosclerotic drugs. Traditional methods for enzyme-based screening exhibit drawbacks of tedious operation steps, reduced enzyme activity, slow mass transfer, as well as high false positive rate. In this paper, an integrated perfusion enzyme affinity selection system based on hollow fiber was constructed to screen hypolipidemic and anti-atherosclerotic compounds from traditional Chinese medicines, and the total saponins of Kudingcha were taken as a case. First, we built a hollow fiber based perfusion system and optimized the methodology for enzyme affinity selection. Then, two active compounds of kudinosides A and C were identified as potential lipase inhibitors from the total saponins of Kudingcha by the proposed system. Last, the activity of kudinosides A and C was verified by lipase inhibitory assay and formation of foam cell model induced by low density lipoprotein aggregates, exhibiting the reliability of the system. This platform shows the advantages of integration, fast mass transfer, simple operation, low cost, as well as improved throughput and efficiency, which is especially suitable for rapid screening active components from traditional Chinese medicine.
摘要
ObjectiveThe mechanism that affects the infiltration of immune cells in pancreatic cancer has not yet been clarified. This study aims to investigate the lncRNA mRNA regulatory pathways that affect immune infiltration in pancreatic cancer.MethodsTCGA and GEO gene expression data were used to screen common differential lncRNAs. We perform survival analysis, target gene prediction, GO, KEGG enrichment analysis, immune infiltration analysis, gene set enrichment analysis (GSEA) on the selected differential lncRNAs to identify the relevant pathways of immune infiltration.ResultsThe pancreatic cancer patients with high expression of ADAMTS9 AS1 have a higher survival rate when compared to patients with low expression (P=0.010). The combined analysis of TCGA and GSE86436 revealed the difference and survival-related ADAMTS9 AS1. The functional prediction of ADAMTS9 AS1 was related to immunity. Using the TIMER database, the lncRNA affected the infiltration of immune cells in pancreatic cancer tissues. The clinical analysis was demonstrated that the ADAMTS9 AS1 was related to pathological grade. The target gene SEMA3G was screened by co-expression analysis using the IMMPORT database and TIMER database. Lastly, GSEA analysis of ADAMTS9-AS1 showed that the lncRNA was also related to tumor metabolism.ConclusionThese results indicate that ADAMTS9-AS1-SEMA3G is associated with the prognosis and immune invasion level of pancreatic cancer, which can provide a theoretical basis for subsequent genetic verification experiments and immune research.