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Objective:To investigate the effects of neonatal respiratory distress syndrome(NRDS)on thymus of premature infants.Methods:We collected baseline data from premature infants with gestational age of 28~32 weeks in neonatal intensive care unit of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 1, 2019 to December 31, 2019.The largest transverse diameter and the sagittal of thymus were measured by ultrasonography within 24 h of birth, then, the thymic index(TI)and thymic weight index(TWI)were calculated to assess the size of thymus.The preterm neonates were divided into NRDS group and non-NRDS group according to the diagnosic criteria of NRDS, and the two groups were then divided into antenatal corticosteroid administration(ACS)group and non-ACS group according to ACS exposure.We then compared the TI and TWI between these groups.Results:One hundred and sixty-three preterm neonates were enrolled in our study, including 98 NRDS preterm neonates and 65 non NRDS preterm neonates.After matching gestational age and birth weight of the preterm neonates from two groups, 65 preterm neonates with NRDS comprised the NRDS group, and 65 preterm neonates without NRDS served as controls.Preterm neonates in NRDS group had significantly smaller TI[(1.788 ± 0.803)cm 3 vs.(2.420±1.068)cm 3, t=3.818, P<0.01] and TWI[(1.278 ± 0.380)cm 3/kg vs.(1.695 ± 0.491)cm 3/kg, t=5.401, P<0.01] than those in non-NRDS group.Besides, preterm neonates in NRDS group had smaller lymphocytes count[(3.729 ± 1.263)×10 9/L vs.(4.437 ± 1.608)×10 9/L, t=2.789, P<0.01] than that in non-NRDS group.For NRDS preterm neonates, TI[(1.487 ± 0.515)cm 3 vs(2.185 ± 0.942)cm 3, t=3.542, P<0.01] ]and TWI[(1.134± 0.311)cm 3/kg vs(1.469± 0.385)cm 3/kg, t=3.882, P<0.01] in ACS group were significantly smaller than those in non-ACS group.For non-NRDS preterm neonates, TI and TWI in ACS group also were significantly smaller than those in non-ACS group( t=2.676、3.659, P<0.05). Conclusion:NRDS is associated with thymic involution of preterm neonates, and ACS exposure affected the size of thymic in premature infants.
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Cardiovascular disease， such as coronary heart disease and acute myocardial infarction， is a leading cause of death globally. Due to the limited proliferative and regenerative capacity of adult mammalian cardiomyocytes （CMs）， any of the current therapies cannot reverse the massive loss of CMs and subsequent fibrosis resulting from cardiac injury. Mammals mainly rely on glycolysis in the embryonic stage and fatty acid oxidation after birth for energy production. Recent reports have indicated that this metabolic pattern switch is closely related to the loss of CM proliferation. In this review， we summarize the biological characteristics of CMs and advances in heart regeneration， meanwhile shed light on the important role of CMs energy metabolism in cardiac regeneration.
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@# Objective To investigate the prevalence of the occupational hazard of organic solvent and noise in printing and Methods record medium production enterprises in Longgang District of Shenzhen City. A total of 56 printing and record medium production enterprises were selected as the study subjects by judgmental sampling method to analyze the worksite Results survey of occupational health and the key occupational hazard factors. There were 256 organic solvent samples ， detected in 56 enterprises which included a total of 148 terms and 1 358 categories of volatile constituents. The top three （ ）， - （ ） （ ） volatile constituents were toluene 35.5% n hexane 25.7% and methanol 23.8% . The top three detected samples of the （ ， ， ， ， - ， ，- ， eight key chemical occupational hazard factors benzene toluene xylene ethylbenzene n hexane 1 2 dichloroethane ） ， - ， trichloroethylene and chloroform were toluene n hexane and ethylbenzene. In the workplace air toluene was the most risk ， factor of occupational hazard factors in enterprise and in sample detection while no trichloromethane was detected. The toluene in workplace air was found to exceed the national standard with the rate of 2.6%. It showed that 27.9% of the work sites were found occupational noise hazard which was over national standard in the 10 key work sites. Only 64.3% and 57.1% enterprises - performed occupational hazard factors detection and occupational health examination. Both none or invalid toxicant proof - facilities accounted for 33.9% of the enterprises. Both none or invalid noise proof facilities accounted for 78.6% of the Conclusion ， - enterprises. The occupational hazards factor of toluene n hexane and noise were serious in printing and record ， medium production enterprises in Longgang District of Shenzhen City and the occupational health management was imperfect. The occupational regulation should be enhanced in this industry.
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Renal fibrosis is a common and irreversible pathological feature of end-stage renal disease caused by multiple etiologies. The role of inflammation in renal fibrosis tissue has been generally accepted. The latest view is that fatty acid metabolism disorder contributes to renal fibrosis. peroxisome proliferator activated receptor-gamma coactivator 1α (PGC1α) plays a key role in fatty acid metabolism, regulating fatty acid uptake and oxidized protein synthesis, preventing the accumulation of lipid in the cytoplasm, and maintaining a dynamic balanced state of intracellular lipid. In multiple animal models of renal fibrosis caused by acute or chronic kidney disease, or even age-related kidney disease, almost all of the kidney specimens show the down-regulation of PGC1α. Upregulation of PGC1α can reduce the degree of renal fibrosis in animal models, and PGC1α knockout animals exhibit severe renal fibrosis. Studies have demonstrated that AMP-activated protein kinase (AMPK), MAPK, Notch, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), epidermal growth factor receptor (EGFR), non-coding RNA (ncRNAs), liver kinase B1 (LKB1), hairy and enhancer of split 1 (Hes1), and other pathways regulate the expression of PGC1α and affect fatty acid metabolism. But some of these pathways interact with each other, and the effect of the integrated pathway on renal fibrosis is not clear.
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Animals , Fatty Acids , Fibrosis , Lipid Metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Renal Insufficiency, ChronicABSTRACT
Objective:To investigate effects of metformin and rosiglitazone in non-obese polycystic ovary syndrome (PCOS) women with insulin resistance.Methods:Totally 200 non-obese PCOS women with insulin resistance in West China Second Hospital of Sichuan University were enrolled into this study from Sep. 2013 to Jun. 2016, and were randomly divided into two treatment groups: metformin group (1 500 mg/d) and rosiglitazone group (4 mg/d). The treatment lasted for 6 months. Their clinical and biochemical parameters were collected and compared.Results:In both groups, menstrual cycles [metformin group (37±4) days, rosiglitazone group (35±4) days] were shorter after treatment for 6 months (both P<0.01). After treatment for 6 months, body mass index [metformin group (21.6±1.6) kg/m 2, rosiglitazone group (21.7±1.7) kg/m 2] decreased in both groups (both P<0.01); decreased LH/FSH ratio (metformin group 1.67±0.80, rosiglitazone group 1.70±0.83) was also observed (both P<0.05). After treatment for 6 months, fasting insulin level [metformin group (13.5±5.1) mU/L, rosiglitazone group (12.7±5.6) mU/L] and homeostasis model assessment-insulin resistance index (metformin group 3.0±1.2, rosiglitazone group 2.8±1.2) were decreased in both groups (all P<0.01). Conclusions:For non-obese PCOS insulin resistance patients, screening of anthropometric and metabolic parameters is necessary. For PCOS with insulin resistance, lifestyle plus insulin sensitizers such as metformin could improve their clinical symptoms, correct the biochemical and metabolic dysfunction.
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Objective:To investigate the clinical characteristics, long-term prognosis and changes of pulmonary function in children with idiopathic pulmonary fibrosis (IPF).Methods:The clinical data, long-term prognosis and changes of pulmonary function of children with IPF admitted to the Department of Pediatric Respiratory Center in Children′s Hospital of Chongqing Medical University from January 2008 to December 2018 were retrospectively analyzed.Results:A total of 28 cases were included, with the median age of 3.9 years (range: 0.5 to 15.7 years). Cough (28 cases, 100.0%), tachypnea (25 cases, 89.3%), cyanosis (19 cases, 67.9%), dyspnea (11 cases, 39.3%), Velcho rales (12 cases, 42.9%), inspiratory three concave sign (11 cases, 39.3%), clubbed fingers and toes (6 cases, 21.4%) and diminished breath sounds (5 cases, 17.9%) were main clinical manifestations.Chest high-resolution computed tomography (HRCT) mainly displayed grid shadow, irregular sac-like light-transparent shadow with ho-neycomb changes and dense shadow, partial (7 cases) pulmonary interstitial emphysema/emphysema/pneumomediastinum.Three cases of lung biopsy showed hyperplasia and consolidation of alveolar space and alveolar septal fibrosis, thickening of alveolar wall and coexistence of new and old lesions.In this group, 4 cases did not receive drug therapy due to other reasons (3 cases abandoned therapy, and 1case died of respiratory and circulatory failure during hospitalization). Twenty-four cases were treated with single or combination of oral Prednisone, N-acetylcysteine and Azithromycin.Eleven cases had improved symptoms when discharged, and 13 cases showed no improvement.Twenty-four cases continued to receive oral medication therapy according to the original protocol.Eight cases were followed up for chest HRCT for 3 months to 4 years, the chest HRCT lesions of 7 cases were similar to before, and those of 1 case increased than before.All cases received telephone follow-up for 2 to 7 years; the maximum duration of medication was 4 years.Twelve cases were lost to follow-up, 7 cases had motion limitation, 3 cases died, and 2 cases had no clinical symptom.Three cases were followed up for pulmonary function for 2 to 3 years, among which 2 cases had pulmonary function decreased than before; 1 case had improvements in forced vital capacity as a percentage of the predicted value and peak expiratory flow as a percentage of the predicted value, but decline in forced expiratory volume in the first se-cond as a percentage of the predicted value.Conclusions:The clinical manifestations of children with IPF are lack of specificity.Chest HRCT is of great value in the diagnosis of IPF and preliminary monitoring of the activity of lesion.In the long-term follow-up, some of cases have improvements in symptoms; pulmonary function mostly decreases, but part of indexes can be improved.
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This case report presents the diagnosis and treatment of a case with subcutaneous sparganosis.
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BACKGROUND@#Since the outbreak of coronavirus disease 2019 (COVID-19), human mobility restriction measures have raised controversies, partly because of the inconsistent findings. An empirical study is promptly needed to reliably assess the causal effects of the mobility restriction. The purpose of this study was to quantify the causal effects of human mobility restriction on the spread of COVID-19.@*METHODS@#Our study applied the difference-in-difference (DID) model to assess the declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time after adjusting for confounders.@*RESULTS@#The DID model showed that a continual expansion of the relative declines over time in 2020. After 4 weeks, population mobility declined by -54.81% (interquartile range, -65.50% to -43.56%). The accrued population mobility declines were associated with the significant reduction of cumulative COVID-19 cases throughout 6 weeks (ie, 1% decline of population mobility was associated with 0.72% [95% CI: 0.50%-0.93%] reduction of cumulative cases for 1 week, 1.42% 2 weeks, 1.69% 3 weeks, 1.72% 4 weeks, 1.64% 5 weeks, and 1.52% 6 weeks). The impact on the weekly new cases seemed greater in the first 4 weeks but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities.@*CONCLUSIONS@#Persistent population mobility restrictions are well deserved. Implementation of mobility restrictions in major cities with large population sizes may be even more important.
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Humans , COVID-19 , China/epidemiology , Cities , SARS-CoV-2ABSTRACT
Pulmonary cavitary lesions in children consist of a group of heterogeneous diseases, mainly caused by infections, and their imaging manifestations can be similar.It is clinically difficult to distinguish them from other lesions such as bullae, cyst, and emphysema.Some scholars have advanced a concept about thin wall(4 mm or less) and thick wall(more than 4mm).People tried to make this distinction by defining cyst as a thin wall and cavity as a thick wall, but there are considerable overlaps between the two categories in etiology and pathophysiology.They are sometimes difficult to distinguish for imageology, and it is still necessary to find the cause of the disease based on the characteristics.This review divides etiology into two categories: infectious and non-infectious etiology.Combined with chest imaging examination, the purpose is to analyze and summarize the features of pulmonary cavitary lesions in children, and provide a diagnostic idea for differentiating various pulmonary cavities to guide clinical treatment.
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【Objective】 To study the effects of different activators and doses on the concentration of growth factor in platelet rich plasma(PRP). 【Methods】 15 healthy volunteers, recruited to prepare PRP by COM.TEC blood cell separator, were divided into 5 groups: PRP group with no activator, Calcium gluconate PRP group, Thrombin 100U/ mL-PRP group, Thrombin 50U/ mL-PRP group, and Thrombin 100U/ml-calcium gluconate -PRP group. The white blood cell count and platelet count in PRP and whole blood were detected. The concentrations of PDGF-AA, TGF-βand VEGF in PRP inactive group and 4 different activators 1 hour after activation were determined by ELISA. 【Results】 The mean concentration of platelets in PRP was 1 462.86×109/L, which was 5.77 times that in the whole blood. The mean concentrations (pg/mL) of PDGF-AA(174 348.00±132 872.39 vs 217 909.67±182 517.96 vs 221 020.38±153 321.51 vs 208 550.35±177 100.47), TGF-β(12 573.14±3 173.20 vs 14 678.45±5 880.96 vs 14 694.39±5 083.90 vs 12 675.65±4 981.83) and VEGF (653.45±489.82 vs 671.61±506.68 vs 690.05±416.13 vs 678.93±501.07) in 4 different activator groups were significantly higher than those in inactivated group (P<0.05). There was no significant difference in the concentrations of PDGF-AA, TGF-βand VEGF among different activators. Platelet concentration(1 462.86±628.41×109/L) in PRP had a strong positive correlation with PDGF concentration (221 020.38±153 321.51 pg/mL)in thrombin 50 U/ mL-PRP group (P<0.05) and TGF-βconcentration(pg/mL) (12 573.14±3 173.20 vs 14 678.45±5 880.96 vs 14 694.39±5 083.90 vs 12 675.65±4 981.83, respectively) in four different activator groups (P<0.05), but had no correlation with VEGF in each group. 【Conclusion】 PRP was prepared by blood cell separator with high purity. There was no difference in the concentrations of PDGF-AA, TGF-βand VEGF among different activators and different thrombin doses. The correlation between platelet concentration and growth factor concentration in PRP was related to the type of activator and growth factor.
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Objective:To explore clinical features, etiology and mechanism of pulmonary bullae in children.Methods:The clinical data of children with diagnosis or suspected diagnosis of pulmonary bullae, including the general situation, etiology, pathogen composition, number and location, prognosis and so on, in the Inpatient Department of Children′s Hospital of Chongqing Medical University from March 1993 to August 2019 were retrospectively analyzed.Results:Among the 163 patients, there were 130 cases of respiratory tract infection, and 11 cases of pneumothorax alone.Totally, 22 cases were found pulmonary bullae in the chest CT examination without typical symptoms.Etiology: viruses accounted for 19.02%(31/163 cases), with mainly respiratory syncytial virus (9.20%, 15/163 cases); bacterial infection took up 28.83%(47/163 cases), mostly Haemophilus influenzae (13/163 cases, 7.98%) and Staphylococcus aureus (10/163 cases, 6.13%). Pulmonary bullae was more common in the right lung (82 cases). It took 7 days to 9 months for bullae to reduce, shrink or disappear.In some cases, there was no significant change in bullae even after 19 months. Conclusion:Pulmonary bullae can be seen in infection, tumor, auto-immune diseases and so on, most of which are bacterial infections.Bullae may exist for a long time.The mechanism of pulmonary bullae may include the narrowing of lumen, followed by the thickening of bronchial wall, ischemic necrosis and alveolar expansion due to the clogging of distal small vessels or capillaries, the degradation of connective tissue and dissociation of elastic tissue, the destruction of the bronchiolar wall, disturbing ion channels and mitochondria metabolism and destroying the connection of epithelial cells.
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Objective:To explore the clinical characteristics and the therapeutic approach in children with pulmonary embolism(PE).Methods:The clinical data of 8 patients with PE who hospitalized at the Children′s Hospital of Chongqing Medical University from March 2001 to October 2018 were retrospectively analyzed.Results:Among the 8 cases with PE, 3 cases were male and 5 cases were female, the age of subjects ranged from 0.6 to 11.7 years old, the median age was 7.96 years old.All of them had underlying diseases, among them, congenital heart disease with infective endocarditis accounted for 37.5%(3 case). Among the 8 cases, 4 cases presented with symptoms of respiratory tract infection, 7 cases had shortness of breath, 5 cases had cough, 3 cases had chest pain, 2 cases had hemoptysis, and 1 case had typical triad of PE with chest pain, dyspnea and hemoptysis.Among the 8 cases, 7 cases did the arterial blood gas analysis and showed hypoxemia; 6 cases did the D-dimer and the value>500 μg/L; 5 cases did the electroca-rdiogram and 4 cases(80.0%) showed sinus tachycardia, and 2 cases(40.0%) had ST-T changes, all of them did echocardiography and 3 cases(37.5%) of which indicated pulmonary artery excrescence, 7 cases of which did spiral CT pulmonary angiography and 5 cases(71.4%) of them prompted pulmonary vascular filling defects, 6 cases(75.0%) of which were embolized in the lower lobe of the lung.Three cases received anticoagulant therapy, and 1 of them was treated with combined thrombectorny, 1 case of them died.Two cases received thrombectomy, 1 case of them died.Three cases were not treated with thrombectomy and anticoagulation therapy, 2 cases of them died.Conclusions:The mortality of PE in children is high.The clinical manifestations of PE in children are not typical and difficult to distinguish from respiratory infections.For children with high risk factors of PE, once clinical symptoms related to PE occur, D-dimer, echocardiography, and spiral CT pulmonary angiography should be done soon for early diagnosis and treatment.
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Objective: To observe the effects of laurocapram and borneol as transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, hormone-sensitive lipase (HSL) and hydroxymethylglutaryl CoA (HMG-CoA) reductase in hyperlipidemia rabbits.Methods: Forty New-Zealand rabbits were randomly divided into 5 groups using the random number table method, with 8 rats in each group. Rabbits in the blank group were fed routinely with a normal diet; rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model. Rabbits in the blank and the model groups were not given any intervention. After the model was prepared successfully, rabbits in the non-transdermal penetration enhancer group received herbal cake-partitioned moxibustion without transdermal penetration enhancers; rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively. After 4 weeks of treatment, the serum was isolated and enzyme-linked immunosorbent assay (ELISA) was applied for the detection of HSL and HMG-CoA reductase. The liver tissues were isolated, and total cholesterol (TC) and triglycerides (TG) were measured by enzymatic methods. One-step method was applied for high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) detection, and transmission turbidimetry was for apolipoprotein A1 (Apo-A1) and apolipoprotein B (Apo-B) detection. Results: The serum concentrations of the drugs in the laurocapram and the borneol groups were significantly higher than those in the non-transdermal penetration enhancer group (both P<0.05); all drug penetrations in the borneol group were significantly higher than those in the laurocapram group (both P<0.05), except for tanshinone ⅡA. Compared with the non-transdermal penetration enhancer group, the HSL was significantly increased while the HMG-CoA reductase was significantly decreased in the laurocapram and the borneol groups (both P<0.05); between groups, the HSL in the borneol group was significantly higher than that in the laurocapram group (P<0.05). Compared with the blank group, the levels of LDL-C, TG, TC and Apo-B in rabbit liver were significantly increased in the model group (P<0.05); compared with the model group, the levels of LDL-C, TG, TC and Apo-B in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups were significantly decreased (all P<0.05); between groups, the TG and TC in the laurocapram group and the LDL-C, TG, TC and Apo-B in the borneol group were significantly lower than those in the non-transdermal penetration enhancer group (all P<0.05), and the TG, LDL-C and Apo-B in the borneol group were significantly lower than those in the laurocapram group (all P<0.05). Compared with the blank group, the HDL-C and Apo-A1 were significantly decreased in the model group (both P<0.05), while compared with the model group, the HDL-C and Apo-A1 were significantly increased in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups (all P<0.05). Between groups, the Apo-A1 in the laurocapram group, the HDL-C and Apo-A1 in the borneol group were significantly higher than those in the non-transdermal penetration enhancer group (all P<0.05).Conclusion: The application of laurocapram and borneol, as transdermal penetration enhancers, in herbal cake-partitioned moxibustion can promote the penetration of the drugs in the herbal cake, increase the levels of HDL-C and Apo-A1, improve the metabolism of HSL and HMG-CoA reductase, and also simultaneously reduce the levels of TC, TG, LDL-C and Apo-B in the liver. The transdermal penetration enhancement effect of borneol is slightly better than or equivalent to that of laurocapram.
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We report a female infant born preterm to a woman at 35 gestational weeks and four days in a normal pregnancy prior to delivery, with normal liquor volume and good maternal and infant outcomes. The baby was transferred to the neonatal department 30 min after birth at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, on March 21, 2020. The infant weighed 2 800 g with 7 and 9 Apgar scores respectively at 1 and 5 min. The mother had been diagnosed with COVID-19 at 26 +6 weeks of pregnancy and the maternal serum level of IgM was negative and that of IgG was 20.77 AU/ml (normal reference <10 AU/ml) before delivery. The baby had hypoglycemia on admission, and the blood sugar stabilized after treatment. Though early mild feeding intolerance occurred, the baby was able to feed normal by eight days after birth. The baby was in good condition during hospitalization and discharged. Throat swab specimens obtained from the infant on the 2nd, 3rd and 8th day after birth for SARS-Cov-2 RNA detection were all negative. On the 2nd and 8th day after birth, SARS-Cov-2 IgM in the neonatal serum were negative, while elevated IgG levels of 30.2 AU/ml and 25.3 AU/ml (normal reference value <10 AU/ml) were observed, suggesting that the infant's IgG antibody of SARS-CoV-2 may have come from the mother. According to this case report, no intrauterine vertical transmission was found in the pregnancy with SARS-CoV-2 infection in the second trimester, while further follow-up is still needed.
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Prohibitin (PHB), an evolutionarily conserved mitochondrial inner membrane protein, is highly expressed in cells that require strong mitochondrial function. Recently, we demonstrated that the deletion of Phb in spermatocytes results in impaired mitochondrial function. In addition, PHB expression in the mitochondrial sheath of human sperm has a significantly negative correlation with mitochondrial reactive oxygen species levels, but a positive one with mitochondrial membrane potential and sperm motility. These results suggest that mitochondrial PHB expression plays a role in sperm motility. However, the mechanism of PHB-mediated regulation of sperm motility remains unknown. Here, we demonstrate for the first time that PHB interacts with protein kinase B (AKT) and exists in a complex with phospho-PHB (pT258) and phospho-AKT in the mitochondrial sheath of murine sperm, as determined using colocalization and coimmunoprecipitation assays. After blocking AKT activity using wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), murine sperm have significantly ( P < 0.05) decreased levels of phospho-PHB (pT258) and the total and progressive motility. Furthermore, significantly ( P < 0.05) lower levels of phospho-PI3K P85 subunit α+γ (pY199 and pY467) and phospho-AKT (pS473; pT308) are found in sperm from infertile asthenospermic and oligoasthenospermic men compared with normospermic subjects, which suggest a reduced activity of the PI3K/AKT pathway in these infertile subjects. Importantly, these sperm from infertile subjects also have a significantly ( P < 0.05) lower level of phospho-PHB (pT258). Collectively, our findings suggest that the interaction of PHB with AKT in the mitochondrial sheath is critical for sperm motility, where PHB phosphorylation (pT258) level and PI3K/AKT activity are key regulatory factors.
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Objective: To study the constituents and metabolites in rat brain after ig administration of Xueshuan Xinmaining Tablet (XXT) based on the serum medicinal chemistry. Methods: The acute blood stasis rat model was replicated by ice bath-adrenalin method, and XXT [1.4 (g∙kg-1∙d-1)] was administered orally for 8 d. The brain samples were collected and pretreated after ig administration for the last time. Then the absorbed prototype constituents and their metabolites in rats plasma were rapidly analyzed and identified by combination of ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and multivariate statistical analysis. Results: Finally, a total of 11 absorbed prototype constituents and three metabolites were identified, including phenanthrene, bufonis venenum oxadiene, and other structural types of compounds. These constituents absorbed into brain may be the potential bioactive components in XXT. Conclusion: The establishment of UPLC-Q-TOF/MS analysis method explained comprehensively the brain migration component of XXT, and provided scientific basis for clarifying its substance basis of pharmacodynamics of this large variety of Chinese medicine.
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Chimeric antigen receptor T (CAR-T) cell therapy is an emerging immunotherapy that has allowed for major breakthroughs in the treatment of hematological neoplasms. However, little progress has been made in the treatment of solid tumors, primarily due to the difficulty in homing to tumor tissues by CAR-T cells during treatment. The complex tumor microenvironment and the barrier function of tumor tissues prevent CAR-T cells from contacting tumor cells, thereby preventing them from exerting their antitumor ac-tivity. This review article summarizes not only the progress made in the study of homing disorders of CAR-T cells in the treatment of solid tumors but also the current methods to overcome these disorders.
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Objective:To observe the effect of moxibustion on the mRNA and protein expressions of heat-shock protein 70 (HSP70) in gastric cancer-bearing rats. Methods: A total of 40 healthy Sprague-Dawley (SD) rats were adaptively fed for one week. The gastric cancer model was prepared by Walker-256 cancer tissue transplantation. After 7 d, 10 rats were randomly selected to verify the successful modeling, and the remaining 30 rats were divided into a model group, a moxibustion group and an infrared group by the random number table method, with 10 rats in each group. After enrollment, the moxibustion group received suspended moxibustion at Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36), (the first group of acupoints) on the 1st day, and suspended moxibustion at bilateral Pishu (BL 20) and Weishu (BL 21), (the second group of acupoints) on the 2nd day, 20 min each time, once a day. Moxibustion was alternately performed every other day at the two groups of acupoints for 21 d. From the day of enrollment, rats in the infrared group were irradiated with the infrared radiation at the stomach area on the 1st day, and at the T12-T13 interspinous region on the 2nd day, 20 min each time, once a day, and the two locations were alternately irradiated every other day for 21 d. During the treatment, rats in the model group were intervened by grasping and fixation without treatment. At the end of the treatment, blood was collected from the inner eye orbit, and the HSP70 expression in peripheral blood was determined by enzyme linked immunosorbent assay (ELISA). Rats were sacrificed, the tumor volume and growth inhibition rate were measured. The position and changes of HSP70 in gastric cancer were observed by streptavidin-perosidase (SP); HSP70 protein expression was determined by ELISA; HSP70 mRNA expression in cancer tissues was determined by reverse transcription-polymerase chain reaction (RT-PCR) assay. Results: In comparison of the model group, the volume growth of the gastric cancer in the moxibustion group was significantly restricted (P＜0.01); the volume growth inhibition rate in the moxibustion group was 37.93%; the HSP70 expression in peripheral blood and the cancer tissues was significantly increased (both P＜0.01); the expression of HSP70 mRNA and HSP70 content in gastric tumor were both obviously increased in the moxibustion group (P＜0.01); and a large amount of HSP70 was released to the outside of cancer cells in the moxibustion group. In comparison of the model group, the volume growth of the gastric cancer in the infrared group was slightly restricted (P＜0.05) with a volume growth inhibition rate of 15.89%; the HSP70 expression in the infrared group was increased significantly in peripheral blood (P＜0.01) and in the gastric cancer tissues (P＜0.05); more HSP70 was released outside of the cancer cells in the infrared group. In comparison of the infrared group, the volume growth of gastric cancer was more restricted in the moxibustion group (P＜0.05), and the HSP70 expression in the gastric cancer tissues was also higher (P＜0.05); more HSP70 was released outside of the cancer cells in the moxibustion group. Conclusion: Moxibustion and infrared treatment inhibit the gastric cancer growth in the gastric cancer-bearing rats, up-regulate the HSP70 expression in gastric cancer tissues, and promote the production and extracellular release of HSP70, and the effect of moxibustion is more obvious.
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Objective:To observe the lipid-lowering effect of different transdermal absorption enhancers applied to the herbal cake-partitioned moxibustion in hyperlipidemia model rabbits, and to explore the possible mechanism. Methods:Forty New-Zealand rabbits were randomly divided into 5 groups using the random number table method, with 8 rats in each group. Rabbits in the blank group were fed routinely with normal diet; rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model. Rabbits in the blank and the model groups were not treated. After the model was prepared, rabbits in the non-transdermal absorption enhancer group received herbal cake-partitioned moxibustion without transdermal absorption enhancer; rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively. After 4 weeks of treatment, serum was collected for enzyme-linked immunosorbent assay (ELISA), and the liver tissues were isolated for immunohistochemistry, quantitative polymerase chain reaction (qPCR) and Western-blotting (WB) detection. Results: Serum ELISA results showed that leptin was significantly decreased in the model group compared with the blank group (P＜0.05); compared with the model group, leptin was significantly increased in the non-transdermal absorption enhancer, the laurocapram and the borneol groups (all P＜0.05); compared with the non-transdermal absorption enhancer group, leptin was significantly increased in the laurocapram group and the borneol group (both P＜0.05); there was no significant difference in leptin between the laurocapram and the borneol groups (P＞0.05). The qPCR results of rabbit liver tissues showed that the mRNA expressions of leptin, Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) in the model group were significantly lower than those in the blank group (all P＜0.05); compared with the model group, the mRNA expressions of leptin, leptin receptor (LR), JAK2 and STAT3 in the non-transdermal absorption enhancer, the laurocapram and the borneol groups were significantly increased (all P＜0.05); compared with the non-transdermal absorption enhancer group, the mRNA expressions of leptin, LR, JAK2 and STAT3 in the laurocapram and the borneol groups were significantly increased (all P＜0.05); compared with the laurocapram group, the mRNA expressions of leptin, LR, JAK2 and STAT3 in the borneol group were significantly increased (P＜0.05). The trend of immunohistochemistry and WB detection results was basically consistent with the qPCR assay results. The immunohistochemistry and WB detection results of phosphorylated JAK2 (phospho-JAK2) and phosphorylated STAT3 (phospho-STAT3) were basically consistent with those of JAK2 and STAT3. Conclusion: The molecular expression of Leptin/JAK2/STAT3 pathway in the hyperlipidemia model rabbits was decreased. The molecular expression of Leptin/JAK2/STAT3 pathway was significantly increased after the herbal cake-partitioned moxibustion. The application of laurocapram and borneol, as transdermal absorption enhancers, in the herbal cake-partitioned moxibustion could more obviously up-regulate the factors of the Leptin/JAK2/STAT3 lipid-regulating pathway than the herbal cake-partitioned moxibustion alone.
ABSTRACT
OBJECTIVE： To rapidly identify chemical components of Zhitong huazheng capsules （shorted for “ZTHZC”）， and to provide reference for further elucidating the pharmacodynamic material basis and overall quality control. METHODS： UPLC-Q-TOF/MS method was adopted to separate the chemical components of ZTHZC. By reviewing literatures that related to chemical components of ZTHZC and its single Chinese traditional medicinal crops， the chemical structure of the chemical components was saved into a .mol format file， and supplemented the UNIFI database. The chemical constituents of ZTHZC were qualitatively analyzed by UNIFI database screening， and validated according to their precise molecular mass， characteristic ions， neutral loss， secondary mass spectrometry cleavage， chromatographic retention behavior， combined reference information and literature reports. RESULTS： A total of 70 chemical components were identified in this experiment， including 38 organic acids and organic acid esters， 8 alkaloids， 9 flavonoids， 5 triterpenoid saponins， 5 aldehydes， 2 ketones， 1 quinone， 1 polyacetylene and 1 monoterpenoid. CONCLUSIONS： This study provides a rapid detection and identification method for chemical components of ZTHZC， and also provides a scientific basis for the clarification of ZTHZC’s quality control and pharmacodynamics.