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AIM: To observe the effect of PCSK9 inhibitors on blood lipid levels and common inflammatory factors in patients with coronary heart disease. METHODS: The clinical data of 201 patients with coronary heart disease who were admitted to the Department of Cardiology of Shanghai East Hospital from April 2020 to June 2021 were retrospectively analyzed. The patients were divided into PCSK9 inhibitor treatment group (101 cases: statin + PCSK9 inhibitor) and control group (100 cases: statin treatment only) according to their medication status. Blood lipids, blood routine, CRP and FIB were re-examined after 1 month of treatment. The changes of blood lipids and inflammatory factors before and after treatment were compared. RESULTS: Before treatment, there was no significant difference in blood lipids, blood routine, CRP and FIB between the two groups (P> 0.05). The levels of sdLDL and Lp(a) were significantly decreased (P< 0.05); the levels of WBC, CRP, N and FIB were significantly decreased (P< 0.05). Compared with the control group, the levels of TC, HDL, LDL-C, CRP and FIB in the PCSK9 inhibitor group were significantly changed (P< 0.05), and the results were statistically significant. CONCLUSION: PCSK9 inhibitors can not only reduce LDL-C levels, but also reduce Lp(a) levels. PCSK9 inhibitors can reduce CRP and FIB levels, suggesting that it can partially improve inflammation in peripheral blood in patients with coronary heart disease.
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The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).
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Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.
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Objective To evaluate the current situation of quality of life and psychological status of pediatric recipients after kidney transplantation and analyze the influencing factors. Methods Ninety-six pediatric recipients undergoing kidney transplantation were enrolled in this study. Baseline data of the recipients were collected. The quality of life was assessed by Pediatric Quality of Life Inventory 3.0 (PedsQLTM3.0). The psychological status was evaluated by Strengths and Difficulties Questionnaire (SDQ). The influencing factors of postoperative quality of life and psychological status of pediatric kidney transplant recipients were subject to univariate and multivariate analyses. Results The total score of quality of life of pediatric kidney transplant recipients was (71±14) and (12.4±5.8) for the total difficulty score. Univariate analysis showed that gender, postoperative body mass index (BMI) and postoperative complications were the influencing factors of the total score of quality of life of pediatric kidney transplant recipients (all P < 0.05). Gender, postoperative complications and follow-up time were the influencing factors of the total difficulty score of pediatric kidney transplant recipients (all P < 0.05). Multivariate analysis demonstrated that gender, postoperative BMI, postoperative complications, dialysis type before kidney transplantation were the influencing factors of postoperative quality of life of pediatric kidney transplant recipients, whereas gender, postoperative complications and follow-up time were the influencing factors of postoperative psychological status (all P < 0.05). Conclusions The quality of life and psychological status of pediatric kidney transplant recipients are good. In clinical practice, special attention should be paid to those children who are female, with low BMI after kidney transplantation, postoperative complications and short follow-up time. Preventive interventions are recommended to further improve the quality of life of the children.
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Objective:To investigate the characteristics of senile neurodegenerative diseases (NDDs) inpatients in south China, especially in Guangdong province, and explore the influencing factors for their medical expenses.Methods:The medical records of 7231 patients with NDDs≥65 years were collected in the electronic health database of our hospital from January 2010 to December 2019, including gender, age, admission ways, chief complaints, length of hospital stays and medical expenses. On the basis of median of the medical expenses (21 345 yuan) of these patients, they were divided into low cost (<21 345 yuan) group and high cost (≥21 345 yuan) group. Univariate Logistic analysis and multivariate Logistic regression analysis were conducted to screen the influencing factors for medical expenses and the independent influencing factors.Results:(1) The main age group of geriatric inpatients with NDDs were 70-79 years (40.96%); the admission source was mainly outpatient (56.70%), and length of hospital stays of a large percent of patients (44.50%) were 8-14 d. (2) From 2010 to 2019, the number of hospitalized geriatric patients with NDDs showed an increasing trend year by year, the overall trend of length of hospital stays was shortened, and the medical expenses showed gradual increase; the causes of hospitalization, percentages of patients caused by infection, abnormal blood pressure and water-electrolyte metabolism disturbances showed decreased trend, percentages of patients caused by heart diseases, cerebrovascular accidents and mental-psychological diseases showed increased trend, and the proportions of patients caused by fracture/trauma/wound injuries were generally stable. The proportion of patients returning home and mortality rate after hospital discharge were declined, and the proportion of patients returning to other medical or community institutions was increased. (3) Living in ICU, length of hospital stays, diabetes, nosocomial infection, chronic kidney disease, urinary tract infection, tumble, body mass index, and anticholinergic drugs were independent risk factors influencing the medical expenses ( P<0.05). Conclusions:An aging trend is noted in patients with NDDs; the number of hospitalized patients and medical expenses increase year by year, and the length of hospital stays gradually decreases. In view of the many factors that influence the medical expenses of this disease, it is suggested to develop the corresponding standardized treatment plan for the main influencing factors in clinical practice.
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The neuroimaging provides a lot of useful information about the neuromechanism of restless legs syndrome (RLS).The voxel-based morphometry and diffusion tensor imaging findings reported brain microstructural abnormalities,which were more consistent concerning levels of white matter and belonged to the sensorimotor and limbic system.Functional magnetic resonance imaging (MRI) studies also demonstrated the neural activity and/or functional connectivity changes in the sensorimotor and limbic network.Positron emission tomography and single photon emission computed tomography studies supported the dysfunction of the dopaminergic pathways involving not only the nigrostriatal but also mesolimbic pathways.Iron-sensitive MRI verified low brain iron content mainly in substantia nigra and thalamus.The primary change might be the reduction of brain iron content,which leads to the dysfunction of the nigrostriatal and mesolimbic dopaminergic pathways and in turn to a dysregulation of sensorimotor and limbic network resulting in the symptoms of RLS.
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Objective To evaluate the efficacy of adductor canal block combined with infiltration anesthesia for postoperative analgesia in the patients undergoing total knee arthroplasty. Methods Sixty pa?tients of both sexes, aged 65-80 yr, weighing 40-80 kg, of American Society of Anesthesiologists physi?cal statusⅠ or Ⅱ, scheduled for elective unilateral total knee arthroplasty, were divided into 3 groups ( n=20 each) using a random number table: single?injection adductor canal block + infiltration anesthesia group ( group A) , single?injection femoral nerve block+infiltration anesthesia group ( group F) , and infil?tration anesthesia group ( group I) . Ultrasound?guided adductor canal block and femoral nerve block were performed with 0.5% ropivacaine 20 ml before induction of anesthesia in A and F groups, respectively. Af?ter completion of the block, all the patients were ventilated through the laryngeal mask airway under general anesthesia. After installation of the knee prosthesis, local infiltration anesthesia was conducted with 0.2%ropivacaine 50 ml around the knee joint. Acetaminophen oxycodone capsule was taken orally one pill every 6 h starting from the morning on 1st day after surgery. When visual analogue scale ( VAS) score > 5, tram?adol 100 mg was injected intramuscularly as rescue analgesic. At 4, 8, 24, 48 and 72 h after surgery, VAS scores at rest and during activity were recorded, the quadriceps strength was measured, and the re?quirement for analgesic drugs and development of adverse reactions were recorded. Results Compared with group I, VAS scores at rest and during activity were significantly decreased at 4, 8, and 24 h after surger?y, and the consumption of tramadol was significantly decreased after surgery in A and F groups ( P<0.05) . The quadriceps strength at 4 and 8 h after surgery was significantly higher in A and I groups than in group F ( P<0.05) . No patients developed serious adverse reactions in the three groups. Conclusion Adductor ca?nal block combined with infiltration anesthesia provides reliable efficacy for postoperative analgesia with little influence on the quadriceps strength in the patients undergoing total knee arthroplasty.
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Although empirically well understood in their clinical administration, volatile anesthetics are not yet well comprehended in their mechanism studies. A major conundrum emerging from these studies is that there is no validated model to assess the presumed candidate sites of the anesthetics. We undertook this study to test the hypothesis that the single-celled Paramecium could be anesthetized and served as a model organism in the study of anesthetics. We assessed the motion of Paramecium cells with Expert Vision system and the chemoresponse of Paramecium cells with T-maze assays in the presence of four different volatile anesthetics, including isoflurane, sevoflurane, enflurane and ether. Each of those volatiles was dissolved in buffers to give drug concentrations equal to 0.8, 1.0, and 1.2 EC50, respectively, in clinical practice. We could see that after application of volatile anesthetics, the swimming of the Paramecium cells was accelerated and then suppressed, or even stopped eventually, and the index of the chemoresponse of the Paramecium cells (denoted as I ( che )) was decreased. All of the above impacts were found in a concentration-dependent fashion. The biphasic effects of the clinical concentrations of volatile anesthetics on Paramecium simulated the situation of high species in anesthesia, and the inhibition of the chemoresponse also indicated anesthetized. In conclusion, the findings in our studies suggested that the single-celled Paramecium could be anesthetized with clinical concentrations of volatile anesthetics and therefore be utilized as a model organism to study the mechanisms of volatile anesthetics.
ABSTRACT
Although empirically well understood in their clinical administration, volatile anesthetics are not yet well comprehended in their mechanism studies. A major conundrum emerging from these studies is that there is no validated model to assess the presumed candidate sites of the anesthetics. We undertook this study to test the hypothesis that the single-celled Paramecium could be anesthetized and served as a model organism in the study of anesthetics. We assessed the motion of Paramecium cells with Expert Vision system and the chemoresponse of Paramecium cells with T-maze assays in the presence of four different volatile anesthetics, including isoflurane, sevoflurane, enflurane and ether. Each of those volatiles was dissolved in buffers to give drug concentrations equal to 0.8, 1.0, and 1.2 EC50, respectively, in clinical practice. We could see that after application of volatile anesthetics, the swimming of the Paramecium cells was accelerated and then suppressed, or even stopped eventually, and the index of the chemoresponse of the Paramecium cells (denoted as I ( che )) was decreased. All of the above impacts were found in a concentration-dependent fashion. The biphasic effects of the clinical concentrations of volatile anesthetics on Paramecium simulated the situation of high species in anesthesia, and the inhibition of the chemoresponse also indicated anesthetized. In conclusion, the findings in our studies suggested that the single-celled Paramecium could be anesthetized with clinical concentrations of volatile anesthetics and therefore be utilized as a model organism to study the mechanisms of volatile anesthetics.