[Effect of TRIM59 Expression Interference on Daunorubicin Chemosensitivity of Chronic Myeloid Leukemia K562 Cells and Its Mechanism].

OBJECTIVE: To investigate the effect of tripipartite motif 59 (TRIM59) expression interference on the chemosensitivity of daunorubicin (DNR) in chronic myeloid leukemia (CML) K562 cells and the related molecular mechanism. METHODS: The expressions of TRIM59 mRNA in bone marrow tissues of patients with CML and K562 cells were detected by RT-qPCR. Liposome-based transfection technology was used to transfect TRIM59-specific siRNA (si-TRIM59) into K562 cells which then were treated with DNR. The proliferation and apoptosis of cells were detected by CCK-8 assay and flow cytometry, respectively, and the expressions of apoptosis-related protein and Wnt/ß-catenin signaling pathway-related protein were detected by Western blot. RESULTS: Compared with the bone marrow tissue of CML patients at the time of initial treatment, the expression of TRIM59 mRNA in bone marrow tissue of CML patients at the time of chemotherapy resistance was significantly increased (P <0.05). Compared with control group, the cell proliferation inhibition rate and apoptosis rate in si-TRIM59 group and DNR group were significantly increased (P <0.05), the expression of Bax, Caspase3 and Cleaved-Caspase3 protein were significantly increased (P <0.05), while the expressions of Bcl-2, Wnt3α, GSK-3ß protein and the ratio of p-ß-catenin/ß-catenin were significantly decreased (P <0.05). Compared with si-TRIM59 group and DNR group, the proliferation inhibition rate and apoptosis rate of si-TRIM59+DNR group were significantly increased (P <0.05), the expression of Bax, Caspase3 and Cleaved-Caspase3 protein were significantly increased, while the expression of Bcl-2, Wnt3α, GSK-3ß protein and the ratio of p-ß-catenin/ß-catenin were significantly decreased (P <0.05). CONCLUSION: TRIM59 expression interference may enhance the chemosensitivity of K562 cells to DNR, and its mechanism may be related to the regulation of Wnt/ß-catenin signaling pathway.

Inflammatory gut as a pathologic and therapeutic target in Parkinson's disease.

Parkinson's disease (PD) remains a significant unmet clinical need. Gut dysbiosis stands as a PD pathologic source and therapeutic target. Here, we assessed the role of the gut-brain axis in PD pathology and treatment. Adult transgenic (Tg) α-synuclein-overexpressing mice served as subjects and were randomly assigned to either transplantation of vehicle or human umbilical cord blood-derived stem cells and plasma. Behavioral and immunohistochemical assays evaluated the functional outcomes following transplantation. Tg mice displayed typical motor and gut motility deficits, elevated α-synuclein levels, and dopaminergic depletion, accompanied by gut dysbiosis characterized by upregulation of microbiota and cytokines associated with inflammation in the gut and the brain. In contrast, transplanted Tg mice displayed amelioration of motor deficits, improved sparing of nigral dopaminergic neurons, and downregulation of α-synuclein and inflammatory-relevant microbiota and cytokines in both gut and brain. Parallel in vitro studies revealed that cultured dopaminergic SH-SY5Y cells exposed to homogenates of Tg mouse-derived dysbiotic gut exhibited significantly reduced cell viability and elevated inflammatory signals compared to wild-type mouse-derived gut homogenates. Moreover, treatment with human umbilical cord blood-derived stem cells and plasma improved cell viability and decreased inflammation in dysbiotic gut-exposed SH-SY5Y cells. Intravenous transplantation of human umbilical cord blood-derived stem/progenitor cells and plasma reduced inflammatory microbiota and cytokine, and dampened α-synuclein overload in the gut and the brain of adult α-synuclein-overexpressing Tg mice. Our findings advance the gut-brain axis as a key pathological origin, as well as a robust therapeutic target for PD.

Modern Appraisal of Patency and Complications in Cerebral Bypass Surgery: A Single Institution Experience.

BACKGROUND: Cerebral bypass is a valuable surgical technique in well-selected patient populations. Updated clinical guidelines and improved surgical techniques warrant a contemporary reevaluation of the complications and patency to inform clinical practice and enhance postoperative patient care. OBJECTIVE: To assess the complication rates and postoperative graft patency for the 3 most common indications for bypass surgery: moyamoya disease, intracranial atherosclerosis, and intracranial aneurysms. METHODS: Perioperative notes of 175 consecutive bypass patients at a single institution were retrospectively identified to evaluate the clinical course and complications of surgery. RESULTS: The rate of total postoperative complications between moyamoya disease (9 of 98, 9.2%), intracranial atherosclerotic disease (7 of 57, 12.3%), and intracranial aneurysm (4 of 20, 20%) was not statistically different (P = .33). Immediate postoperative bypass patency was significantly higher in moyamoya disease (90 of 96, 93.8%) and intracranial atherosclerotic disease (48 of 51, 94.1%) than in intracranial aneurysm (13 of 18, 72.2%; P = .02). Intravenous heparin administration during bypass suturing was negatively associated with immediate postoperative patency (87% heparin patency vs 99% no heparin patency; P = .02). Double-barrel bypass trended toward an increased risk of wound healing complications (2 of 13, 15.4%) compared with the single-barrel bypass technique (4 of 156, 2.6%; P = .07). CONCLUSION: Cerebral bypass surgery remains an excellent surgical treatment for moyamoya disease, intracranial atherosclerosis, and intracranial aneurysms. This study suggests bypass is safer in moyamoya disease and intracranial atherosclerosis. Additional studies to clarify the risk of single-barrel vs double-barrel bypass and intraoperative heparin-stratified complications may be beneficial.

Prevalence of Disability among the Chinese Older Population: A Systematic Review and Meta-Analysis.

BACKGROUND: Disability is an important problem in aging societies globally. However, the research findings of the prevalence of disability have been inconsistent. This study aims to estimate the prevalence of disability and its influencing factors among the Chinese older population from 1979 to 31 July 2021. METHODS: A systematic review and meta-analysis were conducted using both international (PubMed, Web of Science, CBMdisc, PsycINFO, the Cochrane Library, and EMBASE) and Chinese (CNKI, CQVIP, and WanFang) databases. Meta-analysis was performed using a random-effects model to account for heterogeneity. Subgroup analyses were also done. RESULTS: The pooled prevalence of disability across all 97 studies was 26.2% (95% CI: 23.7-28.6%). The estimates varied according to the types of activities of daily living (ADL), gender, age, and region. Studies based on the identification of cases by using the complete ADL scale showed a higher prevalence than those using the basic ADL scale. The prevalence was slightly higher among female older individuals than among male older individuals. The highest rates were seen in older individuals aged 80 years or older. Elders in central China, southwest China, and northwest China were more likely to be BADL-disabled. CONCLUSION: Prevalence of disability among the Chinese older population is high, around 26%. Using standardized diagnostic systems to correctly estimate the prevalence of disability would be helpful for public health professionals in China.

Treating Metastatic Brain Cancers With Stem Cells.

Stem cell therapy may present an effective treatment for metastatic brain cancer and glioblastoma. Here we posit the critical role of a leaky blood-brain barrier (BBB) as a key element for the development of brain metastases, specifically melanoma. By reviewing the immunological and inflammatory responses associated with BBB damage secondary to tumoral activity, we identify the involvement of this pathological process in the growth and formation of metastatic brain cancers. Likewise, we evaluate the hypothesis of regenerating impaired endothelial cells of the BBB and alleviating the damaged neurovascular unit to attenuate brain metastasis, using the endothelial progenitor cell (EPC) phenotype of bone marrow-derived mesenchymal stem cells. Specifically, there is a need to evaluate the efficacy for stem cell therapy to repair disruptions in the BBB and reduce inflammation in the brain, thereby causing attenuation of metastatic brain cancers. To establish the viability of stem cell therapy for the prevention and treatment of metastatic brain tumors, it is crucial to demonstrate BBB repair through augmentation of vasculogenesis and angiogenesis. BBB disruption is strongly linked to metastatic melanoma, worsens neuroinflammation during metastasis, and negatively influences the prognosis of metastatic brain cancer. Using stem cell therapy to interrupt inflammation secondary to this leaky BBB represents a paradigm-shifting approach for brain cancer treatment. In this review article, we critically assess the advantages and disadvantages of using stem cell therapy for brain metastases and glioblastoma.

High resistance to Toxoplasma gondii infection in inducible nitric oxide synthase knockout rats.

Nitric oxide (NO) is an important immune molecule that acts against extracellular and intracellular pathogens in most hosts. However, after the knockout of inducible nitric oxide synthase (iNOS -/-) in Sprague Dawley (SD) rats, these iNOS -/- rats were found to be completely resistant to Toxoplasma gondii infection. Once the iNOS -/- rat peritoneal macrophages (PMs) were infected with T. gondii, they produced high levels of reactive oxygen species (ROS) triggered by GRA43 secreted by T. gondii, which damaged the parasitophorous vacuole membrane and PM mitochondrial membranes within a few hours post-infection. Further evidence indicated that the high levels of ROS caused mitochondrial superoxide dismutase 2 depletion and induced PM pyroptosis and cell death. This discovery of complete resistance to T. gondii infection, in the iNOS -/--SD rat, demonstrates a strong link between NO and ROS in immunity to T. gondii infection and showcases a potentially novel and effective backup innate immunity system.

Protective effect of Lactobacillus-containing probiotics on intestinal mucosa of rats experiencing traumatic hemorrhagic shock.

This study was conducted to assess whether Lactobacillus-containing probiotics could protect intestinal mucosa in rats during traumatic hemorrhagic shock and to determine its underlying mechanisms. Healthy male Sprague-Dawley rats (300 ± 20 g) were randomly divided into four groups. During the study, reverse transcription polymerase chain reaction, western blotting, and hematoxylin and eosin methods were used. There was a significant increase in the expression of toll-like receptor 4 (TLR4) in the rats that experienced traumatic hemorrhagic shock, along with increased mRNA of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. Pretreatment with Lactobacillus-containing probiotics reduced TLR4 expression, decreased phosphorylation (Ser536) and acetylation (Lys310) of p65, and decreased TNF-α and IL-6 mRNA. The probiotics combined acetate Ringer's group showed a less severe pathological manifestation compared to the other experimental groups. Lactobacillus-containing probiotics inhibited nuclear factor-kappa B signaling via the downregulation of TLR4, resulting in inflammatory homeostasis, which might be the mechanism whereby Lactobacillus protects the intestinal mucosa from damage caused by the traumatic hemorrhagic shock.

Inflammatory Factors as Potential Markers of Early Neurological Deterioration in Acute Ischemic Stroke Patients Receiving Endovascular Therapy - The AISRNA Study.

BACKGROUND AND PURPOSE: This study aimed to explore several peripheral blood-based markers related to the inflammatory response in a total of 210 patients with acute ischemic stroke (AIS) caused by large artery occlusion in the anterior circulation who received endovascular therapy (EVT) from an observational study of clinical significance of circulating non-coding RNA in acute ischemic stroke (AISRNA). METHODS: We collected baseline characteristics of 210 AIS patients participating in an observational acute stroke cohort: the AISRNA study. The following inflammatory factors were measured in these participants: interleukin-2 [IL-2], IL-4, IL-6, IL-10, tumor necrosis factor-α [TNF-α], and interferon-γ [IFN-γ]. The National Institute of Health Stroke Scale score increase of ≥4 within 24 hours after EVT defined as early neurological deterioration (END). RESULTS: Compared with patients without END, patients with END had a higher incidence of atrial fibrillation (P=0.012), and also had higher levels of IL-6 and IL-10 (P<0.01). Furthermore, we found that the area under the curves (AUCs) of IL-6 and IL-10 for predicting END were 0.768 (0.697-0.829), and 0.647 (0.570-0.719), respectively. Adjusting for age, sex, and atrial fibrillation, the odds ratios (ORs; 95% confidence interval) for incident END for IL-6 and IL-10 were 1.98 (1.05-6.69) and 1.18 (1.04-1.33), respectively. Additionally, we found significant changes over time in the expression levels of IL-4, IL-6, and IL-10 in patients with END compared with patients without END (P<0.05). CONCLUSION: IL-6 and IL-10 levels at admission may be potential markers of END after EVT, and the time course of IL-4, IL-6, and IL-10 is correlated with stroke progression. Further larger studies are needed to confirm the current findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04175691. Registered November 21, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691.

Clinical significance of stroke nurse in patients with acute ischemic stroke receiving intravenous thrombolysis.

BACKGROUND: Reports have proven that shorter door-to-needle time (DTN time) indicates better outcomes in AIS patients received intravenous thrombolysis. Efforts have been made by hospitals and centers to minimize DTN time in many ways including introducing a stroke nurse. However, there are few studies to discuss the specific effect of stroke nurse on patients' prognosis. This study aimed to compare consecutive AIS patients before and after the intervention to analyze the effect of stroke nurse on clinical outcome of AIS patients. METHODS: In this retrospective study, we observed 1003 patients from November 2016 to December 2020 dividing in two groups, collected and analyzed AIS patients' medical history, clinical assessment information, important timelines, 90 mRS score, etc. Comparative analysis and mediation analysis were also used in this study. RESULTS: A total of 418 patients was included in this study, and 199 patients were enrolled in the stroke nurse group and 219 was in the preintervention group. Baseline characteristics of patients showed no significant difference except there seems more patients with previous ischemic stroke history in the group of stroke nurse. (p = 0.008). The median DTN time significantly decreased in the stroke nurse group (25 min versus 36 min, p < 0.001) and multivariate logistic regression analysis showed the 90-day mRS clinical outcome significantly improved in the stroke nurse group (p = 0.001). Mediation analysis indicated the reduction of DTN time plays a partial role on the 90 days mRS score and the stroke nurse has some direct effect on the improvement of clinical outcome (p = 0.006). CONCLUSIONS: The introduction of stroke nurse is beneficial to clinical outcome of AIS patients and can be use of reference in other hospitals or centers.

Combination of Stem Cells and Rehabilitation Therapies for Ischemic Stroke.

Stem cell transplantation with rehabilitation therapy presents an effective stroke treatment. Here, we discuss current breakthroughs in stem cell research along with rehabilitation strategies that may have a synergistic outcome when combined together after stroke. Indeed, stem cell transplantation offers a promising new approach and may add to current rehabilitation therapies. By reviewing the pathophysiology of stroke and the mechanisms by which stem cells and rehabilitation attenuate this inflammatory process, we hypothesize that a combined therapy will provide better functional outcomes for patients. Using current preclinical data, we explore the prominent types of stem cells, the existing theories for stem cell repair, rehabilitation treatments inside the brain, rehabilitation modalities outside the brain, and evidence pertaining to the benefits of combined therapy. In this review article, we assess the advantages and disadvantages of using stem cell transplantation with rehabilitation to mitigate the devastating effects of stroke.

Mesenchymal Stem Cell-Induced Anti-Neuroinflammation Against Traumatic Brain Injury.

Traumatic brain injury (TBI) is a pervasive and damaging form of acquired brain injury (ABI). Acute, subacute, and chronic cell death processes, as a result of TBI, contribute to the disease progression and exacerbate outcomes. Extended neuroinflammation can worsen secondary degradation of brain function and structure. Mesenchymal stem cell transplantation has surfaced as a viable approach as a TBI therapeutic due to its immunomodulatory and regenerative features. This article examines the role of inflammation and cell death in ABI as well as the effectiveness of bone marrow-derived mesenchymal stem/stromal cell (BM-MSC) transplants as a treatment for TBI. Furthermore, we analyze new studies featuring transplanted BM-MSCs as a neurorestorative and anti-inflammatory therapy for TBI patients. Although clinical trials support BM-MSC transplants as a viable TBI treatment due to their promising regenerative characteristics, further investigation is imperative to uncover innovative brain repair pathways associated with cell-based therapy as stand-alone or as combination treatments.

Stem Cells for Aging-Related Disorders.

This review captures recent advances in biological and translational research on stem cells. In particular, we discuss new discoveries and concepts regarding stem cell treatment of aging-related disorders. A myriad of stem cell sources exists, from hematopoietic to mesenchymal and neural cell lineages. We examine current applications of exogenous adult bone marrow-derived stem cells as an effective and safe transplantable cell source, as well as the use of electrical stimulation to promote endogenous neurogenesis for Parkinson's disease. We also explore the potential of transplanting exogenous umbilical cord blood cells and mobilizing host resident stem cells in vascular dementia and aging. In addition, we assess the ability of small molecules to recruit resident stem cells in Alzheimer's disease. Finally, we evaluate mechanisms of action recently implicated in stem cell therapy, such as the role of long non-coding RNAs, G-protein coupled receptor 5, and NeuroD1. Our goal is to provide a synopsis of recent milestones regarding the application of stem cells in aging.

[Clinical Value of 1.5-T Non-contrast Whole-heart Magnetic Resonance Coronary Angiography in Evaluating the Severity of Coronary Stenosis].

Objective To evaluate the diagnostic performance of 1.5-T non-contrast free-breathing whole-heart magnetic resonance coronary angiography(MRCA)for≥50% and≥70% coronary artery stenosis in coronary artery disease(CAD).Methods Forty-one patients clinically scheduled for invasive coronary angiography(ICA)underwent 1.5-T non-contrast free-breathing whole-heart MRCA.The diagnostic performance for≥50% and≥70% stenosis was evaluated and compared using ICA as a reference standard.Results MRCA was completed in all the 41 patients with the total acquisition time of(10.1 ± 2.2)min.The sensitivity,specificity,and accuracy of MRCA for≥50% and≥70% stenosis were 100%(95% CI:89%-100%)and 82%(95%CI:63%-94%),38%(95%CI:9%-76%)and 54%(95%CI:25%-81%),and 88%(95%CI:73%-95%)and 73%(95%CI:57%-85%)on a per-patient basis,respectively;they were 95%(95%CI:87%-99%)and 86%(95%CI:73%-95%),58%(95%CI:45%-71%)and 76%(95%CI:65%-85%),and 78%(95%CI:69%-84%)and 80%(95%CI:71%-86%)on a per-vessel basis,respectively.The sensitivity of MRCA for≥50% stenosis was higher than that for≥70% stenosis(97%vs.88%,χ 2=5.73,P=0.017),and the specificity showed an opposite trend(86% vs. 94%,χ 2=14.12,P<0.001)on a per-segment basis.Conclusions The 1.5-T non-contrast whole-heart MRCA can detect both≥50% and≥70% coronary artery stenosis with high sensitivity and accuracy.MRCA showed lower sensitivity while higher specificity for≥70% stenosis than for≥50% stenosis on a per-segment basis.

An Examination of Mobile Spinal Cord Stimulators on Treating Parkinson Disease.

In animal models of Parkinson disease (PD), spinal cord stimulation (SCS) exhibits neuroprotective effects. Recent advancements in SCS technology, most importantly mobile stimulators, allow for the conventional limitations of SCS such as limited stimulation time and restricted animal movements to be bypassed, offering potential avenues for improved clinical translation to PD patients. Small devices that could deliver continuous SCS to freely moving parkinsonian rats were shown to significantly improve behavior, preserve neurons and fibers in the substantia Nigra/striatum, reduce microglia infiltration, and increase laminin-positive area of the cerebral cortex. Through possible anti-inflammatory and angiogenic mechanisms, it has been demonstrated that there are behavioral and histological benefits to continuous SCS in a time-dependent manner. This review will discuss the benefits of this technology as well as focus on the limitations of current animal models.

IL-2/IL-2R Antibody Complex Enhances Treg-Induced Neuroprotection by Dampening TNF-α Inflammation in an In Vitro Stroke Model.

The present in vitro study showed that IL-2/IL-2R antibody complex facilitates Treg-induced neuroprotection in the oxygen glucose deprivation/reoxygenation (OGD/R) model of stroke. First, we examined the role of IL-2/IL-2R-treated Tregs in OGD/R-exposed rat primary cortical cells (PCCs), which represent the cell type of the ischemic gray matter in the stroke brain. Here, OGD/R induced cell death, which was attenuated by Tregs and more robustly by IL-2/IL-2R-treated Tregs, but not by IL-2/IL-2R treatment alone. Second, we next assessed IL-2/IL-2R effects in OGD/R-exposed human oligodendrocyte progenitor cells (OPCs), which correspond to the white matter injury after stroke. Results revealed that a similar pattern neuroprotection as seen in the gray matter, in that OGD/R triggered cell death, which was ameliorated by Tregs and more effectively by IL-2/IL-2R-treated Tregs, but IL-2/IL-2R treatment alone was not therapeutic. Third, as we begin to understand the mechanism underlying IL-2/IL-2R engagement of Tregs, we investigated the inflammatory response in OGD/R-exposed human neural progenitor cells (NPCs), which recapitulate both ischemic gray and white matter damage in stroke. Similar to PCCs and OPCs, OGD/R produced cell death and was blocked by Tregs and more efficiently by IL-2/IL-2R-treated Tregs, whereas IL-2/IL-2R treatment alone did not alter the ischemic insult. Moreover, the inflammatory marker, TNF-α, was upregulated after OGD/R, dampened by both Tregs and more efficiently by IL-2/IL-2R-treated Tregs but more pronounced in the latter, and not affected by IL-2/IL-2R treatment alone, suggesting IL-2/IL-2R-Treg-mediated modulation of inflammatory response in stroke. Altogether, these observations support the use of IL-2/IL-2R treatment in enhancing the anti-inflammatory effects of Tregs in stroke.

Pituitary Adenylate Cyclase-Activating Polypeptide: A Potent Therapeutic Agent in Oxidative Stress.

Stroke is a life-threatening condition that is characterized by secondary cell death processes that occur after the initial disruption of blood flow to the brain. The inability of endogenous repair mechanisms to sufficiently support functional recovery in stroke patients and the inadequate treatment options available are cause for concern. The pathology behind oxidative stress in stroke is of particular interest due to its detrimental effects on the brain. The oxidative stress caused by ischemic stroke overwhelms the neutralization capacity of the body's endogenous antioxidant system, which leads to an overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and eventually results in cell death. The overproduction of ROS compromises the functional and structural integrity of brain tissue. Therefore, it is essential to investigate the mechanisms involved in oxidative stress to help obtain adequate treatment options for stroke. Here, we focus on the latest preclinical research that details the mechanisms behind secondary cell death processes that cause many central nervous system (CNS) disorders, as well as research that relates to how the neuroprotective molecular mechanisms of pituitary adenylate cyclase-activating polypeptides (PACAPs) could make these molecules an ideal candidate for the treatment of stroke.

Distribution of Lactoferrin Is Related with Dynamics of Neutrophils in Bacterial Infected Mice Intestine.

Lactoferrin (Lf) is a conserved iron-binding glycoprotein with antimicrobial activity, which is present in secretions that recover mucosal sites regarded as portals of invaded pathogens. Although numerous studies have focused on exogenous Lf, little is known about its expression of endogenous Lf upon bacterial infection. In this study, we investigated the distribution of Lf in mice intestine during Escherichia coli (E. coli) K88 infection. PCR and immunohistology staining showed that mRNA levels of Lf significantly increased in duodenum, ileum and colon, but extremely decreased in jejunum at 8 h and 24 h after infection. Meanwhile, endogenous Lf was mostly located in the lamina propria of intestine villi, while Lf receptor (LfR) was in the crypts. It suggested that endogenous Lf-LfR interaction might not be implicated in the antibacterial process. In addition, it was interesting to find that the infiltration of neutrophils into intestine tissues was changed similarly to Lf expression. It indicated that the variations of Lf expression were rather due to an equilibrium between the recruitment of neutrophils and degranulation of activated neutrophils. Thus, this new knowledge will pave the way to a more effective understanding of the role of Lf in intestinal mucosal immunity.

[The relationship between heart rate inflection point and lactate recovery and lung function in healthy adults at the Plateau].

Objective: To explore the relationship between heart rate deflection point (HRDP) and blood lactate recovery ability and lung function of healthy people aged 20～40 years old in a plateau environment of 3 200 m. Methods: 225 healthy people aged 20～40 who lived on a plateau of 3 200 m were used as the research subjects. The HRDP strength, heart rate recovery ability and blood lactate recovery ability were evaluated by the changes of heart rate and blood lactate recovery before, during and after the modified Conconi test. Results: ①The heart rate of the subjects increased with the increase in exercise intensity, and the heart rate of the recovery period after exercise showed a downward trend, the rate of Conconi test center was significantly lower in male than that in female(P＜ 0.05). At the same age, male HRDP appeared later, and female HRDP appeared earlier. At the same sex stage, the time of HRDP appeared earlier in the male group with increasing age, while the phenomenon in the female group was not significant. HRDP speed had a downward trend with age. ②The inflection point concentration of blood lactic acid in the subjects gradually decreased with age, but there was no significant difference between the low-age group and the high-age group; the blood lactic acid level in the Conconi test of healthy adult males living on the plateau was significantly lower than that of females(P＜0.05). ③FVC, MVV, FEV1 and FEV1/FVC levels in each gender group showed a downward trend with age, and the data of the male group and above were significantly higher than the female group of the same age (P＜0.05). ④Load-Heart Rate curve and Heart Rate-Blood Lactate fitting curve showed that the correlation coefficients of the male group were 0.8345, 0.8954, 0.8680, and 0.8892 in sequence; the correlation coefficients of the female group were in sequence 0.9318, 0.9661, 0.9663 and 0.9599. HRDP values of all genders and age groups were significantly correlated with their MVV levels (P＜0.05). Except for subjects 36～40 years old in the male group, lung function and lactate elimination rate of all genders and age groups were also significantly correlated (P＜0.05). Conclusion: There are age and gender differences in exercise heart rate response rules and respiratory system functions of healthy people aged 20～40 years old living on 3 200 m plateau. There is a significant correlation between HRDP and lactic acid recovery capacity and lung function. The above indicators can be used to assess the aerobic exercise endurance ability of healthy adults living on plateau.

Research on the establishment of a TPM3 monoclonal stable transfected PANC-1 cell line and the experiment of the EMT occurrence in human pancreatic cancer.

Background: Pancreatic cancer is one of the most aggressive human malignancies that is associated with early metastasis and chemoresistance. Tropomyosin (TPM) is an indispensable regulatory protein for muscle contraction, Abnormal expressions of TPM gene are closely related to the carcinogenesis and metastasis of malignant tumors. Purpose: In this experiment, a monoclonal stable transfected cell line was established by the knock-down of TMP3 expression in PANC-1 cells with the lentivirus method, and the impacts of the downregulated TPM3 gene expression on the EMT-related molecules and biological behaviors of PANC-1 cells were explored. Methods: Based on the TPM3 gene sequence, we designed the RNA interference sequence, constructed and screened out the recombinant plasmid segment TPM3-shRNA with the optimal silencing effect, and carried out lentivirus titer determination and packaging. The recombinant lentiviral interference vector LV-TPM3-shRNA was transfected into PANC-1 cells; the transfection efficiency was then evaluated to screen out the monoclonal stable transfected PANC-1 cell line with downregulated TPM3 expression. The qRT-PCR and Western blot were used to detect the changes in the gene- and protein-levels expressions of EMT-related transcription factors in the target cell line and to respectively test the variations of the invasion and proliferation capacities. Results: It is shown that the monoclonal stable transfected PANC-1 cell line with downregulated TPM3 expression was successfully established with the recombinant lentiviral vector. After knocking down the expression of TPM3 gene in PANC-1 cells, EMT occurred in the cells; the cell phenotype showed malignant transformation, and the in vitro biological behaviors of the cells (such as proliferation and invasion) were enhanced to different degrees. Conclusion: It is indicated that the TPM3 gene can be a potential target spot for the treatment of pancreatic cancer.

Serum uric acid levels and hyperuricemia in patients with psoriasis: a hospital-based cross-sectional study

Abstract: A hospital-based cross-sectional study was performed, including 117 psoriatic patients and 117 controls matched for age, gender, and body mass index. Psoriatic patients had higher levels of serum uric acid (6.25 ± 1.62 vs 5.71 ± 1.35 mg/dl; P=0.019) and significantly greater prevalence of hyperuricemia (31.6% vs 16.2%; P=0.009) than individuals without psoriasis. Psoriatic patients had significantly higher serum uric acid than controls in subjects without metabolic syndrome. Multivariate logistic regression analysis showed that psoriasis can be a strong predictor of hyperuricemia (odds ratio 2.61; 95% confidence interval 1.34-5.00; P=0.004).