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Objective: To study the effect of diurnal temperature range on the number of elderly inpatients with ischemic stroke in Hunan Province. Method: Demographic and disease data, meteorological data, air quality data, population, economic and health resource data of elderly inpatients with ischemic stroke were collected in 122 districts/counties of Hunan Province from January to December 2019. The relationships between the diurnal temperature range and the number of elderly inpatients with ischemic stroke were analyzed by using the distributed lag non-linear model, including the cumulative lag effect of the diurnal temperature range in different seasons, extremely high diurnal temperature range and extremely low diurnal temperature range. Results: In 2019, 152 875 person-times were admitted to the hospital for ischemic stroke in the elderly in Hunan Province. There was a non-linear relationship between the diurnal temperature range and the number of elderly patients with ischemic stroke, with different lag periods. In spring and winter, with the decrease in diurnal temperature range, the risk of admission of elderly patients with ischemic stroke increased (Ptrend<0.001, Ptrend=0.002);in summer, with the increase in diurnal temperature range, the risk of admission of elderly patients with ischemic stroke increased (Ptrend=0.024);in autumn, the change in the diurnal temperature range would not cause a change in admission risk (Ptrend=0.089). Except that the lag effect of the extremely low diurnal temperature range in autumn was not obvious, the lag effect occurred in other seasons under extremely low and extremely high diurnal temperature ranges. Conclusion: The high diurnal temperature range in summer and the low diurnal temperature range in spring and winter will increase the risk of admission of elderly patients with ischemic stroke, and the risk of admission of elderly patients with ischemic stroke will lag under the extremely low and extremely high diurnal temperature ranges in the above three seasons.
Subject(s)
Humans , Aged , Temperature , Ischemic Stroke , Inpatients , Cold Temperature , Hot Temperature , Seasons , China/epidemiologyABSTRACT
Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.
Subject(s)
Animals , Caenorhabditis elegans/metabolism , Cation Transport Proteins/genetics , Homeostasis , Mitochondria/metabolism , Zinc/metabolismABSTRACT
Objective:To quantitatively evaluate the energy loss (EL) and vortex characteristics in the left ventricle by vector flow mapping (VFM) technique in heart failure patients with mid-range ejection fraction (HFmrEF) and reduced ejection fraction (HFrEF).Methods:One hundred and five patients in Qilu Hospital of Shandong University from October 2016 to November 2017 with heart failure and left ventricular ejection fraction (LVEF)<50% were enrolled and divided into HFmrEF Group (LVEF40%~<50%, 56 cases) and HFrEF group (LVEF<40%, 49 cases). Another 32 healthy people at the same period were matched as control group. The EL, vortex area and circulation of isovolumic relaxation phase (IVR), rapid filling phase (RFP), atrial contraction phase (ACP), isovolumic contraction phase (IVC) and rapid ejection phase (REP) in the left ventricle was measured by VFM technique.Results:The EL in HFmrEF group and HFrEF group was lower than that in the control group. In ACP, the EL was gradually decreased among the control group, HFmrEF group and HFrEF group( P<0.05). In ACP, the vortex area and circulation was larger in heart failure patients than those in the control group, and gradually increased from control group, to HFrEF group( P<0.05). Positive correlation between EL and E/e ′ was evidenced in the RFP ( r=0.524, P< 0.001). While in ACP, there was a positive correlation between EL and A peak ( r=0.492, P<0.001), and a negative correlation between EL and vortex area ( r=-0.235, P=0.040). Conclusions:VFM can be applied to evaluate the EL in left ventricle. The EL in the left ventricle of patients with HFmrEF and HFrEF is significantly lower than that in control group. El is correlated with cardiac systolic and diastolic function and vortex area.
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<b>Objective::To compare the protective effect of different bile (porcine bile, oxgall and sheep bile) and their Arisaema cum Bile on rats with acute lung injury, so as to provide reference for the selection of bile and the classification of decoction pieces of Arisaema cum Bile. <b>Method::Wistar male rats were randomly divided into 8 groups (<italic>n</italic>=12), including blank group, model group, porcine bile group, oxgall group, sheep bile group, Arisaema cum Bile with porcine bile group, Arisaema cum Bile with oxgall group and Arisaema cum Bile with sheep bile group. Rats in each treatment group were given corresponding drug solution by gavage at 2.52 g·kg<sup>-1</sup> every day, and rats in the model group and the blank group were given the same volume of normal saline by gavage every day for a total of 8 days. On the 8<sup>th</sup> day, after 1 h of administration, rats in the model group and each treatment group were intraperitoneally injected lipopolysaccharide (LPS, 2 mg·kg<sup>-1</sup>) to prepare rat lung injury model. Blood and lung tissues were collected from every four rats at 3, 6, 24 h after LPS injection, respectively. Lung coefficient, lung water content and wet weight/dry weight ratio of lung tissue (<italic>W</italic>/<italic>D</italic>) were measured, and the levels of tumor necrosis factor (TNF)-<italic>α</italic>, interleukin (IL)-6 and thromboxane B<sub>2</sub> (TXB<sub>2</sub>) in serum and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the contents of malondialdehyde (MDA) and matrix metalloproteinase-9 (MMP-9) in lung tissue were determined by enzyme linked immunosorbent assay (ELISA). The pathological morphology of rat lung tissue was observed and the score of lung tissue injury was calculated. <b>Result::Compared with the model group at the same time point, the lung coefficient, <italic>W</italic>/<italic>D,</italic> lung water content, contents of TNF-<italic>α</italic>, IL-6 and TXB<sub>2</sub> in serum, contents of MDA and MMP-9 in lung tissue of rats in each treatment group were all decreased, and most of them had significant differences (<italic>P</italic><0.05, <italic>P</italic><0.01), but the activities of GSH-Px and SOD were all increased, and most of them had significant differences (<italic>P</italic><0.05, <italic>P</italic><0.01). The oxgall group and the sheep bile group were superior to the porcine bile group in most of the indexes, the Arisaema cum Bile with oxgall group and the Arisaema cum Bile with sheep bile group were superior to the Arisaema cum Bile with porcine bile group, and some of them had significant differences(<italic>P</italic><0.05, <italic>P</italic><0.01). <b>Conclusion::Each bile group and each Arisaema cum Bile group all have protective effects on rats with acute lung injury induced by LPS, and the therapeutic effect of oxgall and sheep bile is better than that of porcine bile, the therapeutic effect of Arisaema cum Bile prepared by oxgall and sheep bile is better than that of Arisaema cum Bile prepared by porcine bile.
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OBJECTIVE: To prepare and characterize triptolide cubic liquidcrystal,study the rheological properties and in vitro transdermal properties. METHODS: Cubic liquid crystal (V2) was prepared by using phytantriol-carbitol-water three-component system. Using the ternary phase diagram method to optimize the target area. V2 was characterized by small-angle X-ray scattering, infrared spectroscopy and differential scanning calorimetry. Rheological properties of V2 was studied by a DHR-2 rheometer. In vitro drug release studies were conducted by using improved Franz diffusion cell method. RESULTS: SAXS is shown as double-diamond lattice cubic liquid crystal; rheological parameters are good; DSC results show V2 can be converted into a hexagonal phase at 65.5 ℃ and converted into a layered liquid crystal at 90 ℃, and the addition of the drug does not change the liquid crystal structure. In vitro transdermal cumulative permeation amount is about 1.54 times that of the gel, and the sustained release of triptolide can be as long as 48 h. CONCLUSION: The prepared triptolide liquid crystal has good appearance and suitable rheology, and its cumulative permeation amount and infiltration rate of V2 are superior to the hydrophilic gel, which provides theoretical reference for triptolide percutaneous administration.
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Liquid crystalline nanoparticles are composed of a certain concentration of amphiphilic lipid self-assembly in water. The attractiveness of this formulation is linked to the nanostructural versatility, compatiblity, digestiblity and bioadhesive properties of their lipid constituents, and the capability of solubilizing and sustaining the release of amphiphilic, hydrophobic and hydrophilic drugs. Liquid crystalline nanoparticles, as a novel drug delivery system, have great promise in drug delivery. The carrier materials, preparation methods, characterization and applications of liquid crystalline nanoparticles were reviewed based on relevant articles published in recent years to provide reference for further study of liquid crystal nanoparticles.
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Objective: To investigate the clinical significance of tumor associated macrophages (TAM) in multiple myeloma (MM) and the relationship with angiogenesis and immunosuppression. Methods: Seventy cases of MM patients diagnosed from August 2015 to June 2017 were enrolled in the study as experimental group, 20 cases of benign hematological diseases (13 with iron deficiency anemia and 7 with megaloblastic anemia) patients as control group. Immunohistochemical method was used to detect the expression of CD163, CD34 and VEGF in bone marrow samples, and flow cytometry was used to detect the proportion of regulatory T cell (Treg cells), ELISA was used to detect the level of IL-10, and the clinical features were analyzed. Results: ①Among the 70 patients, there were 31 males and 39 females with a median age of 65 (50~78) years old. TAM infiltration density, microvascular density (MVD), VEGF expression level, Treg ratio and IL-10 level in bone marrow samples of 70 MM patients were significantly higher than those of benign hematological diseases (P<0.05). ②In the MM group, the above indexes of the patients with disease stabilized (15 cases) were lower than those of the newly diagnosed group (35 cases) and the relapse refractory group (20 cases) (P<0.05), those of relapse refractory group were higher than those of newly diagnosed group (P>0.05). ③Of the 35 newly diagnosed MM patients, 27 completed 4 courses of treatment. In the effective group (15 cases), the TAM infiltration density after treatment was significantly lower than that before treatment, the difference was statistically significant[(20.20±7.66) vs (28.87±11.97), t=2.362, P=0.025]; while in the ineffective group of 12 cases, the difference of the TAM infiltration density before and after treatment was not statistically significant[(42.00±13.76) vs (48.25±13.59), t=1.119, P=0.275]. ④TAM infiltration density in the effective group after bortezomib treatment (21 cases) were lower than those in the non-bortezomib treatment group (18 cases)[(16.52 ±4.26) vs (19.27 ±5.82), t=1.662, P=0.170]. ⑤The TAM infiltration density in MM patients was positively correlated with MVD, VEGF expression level, Treg cell ratio and IL-10 level (P<0.001). Conclusion: The infiltration of TAM in the microenvironment of MM, which may promoting angiogenesis and inhibiting immune response, is related to the occurrence, development, therapeutic effect and drug resistance of MM.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Macrophages , Multiple Myeloma , Neoplasm Recurrence, Local , Neovascularization, PathologicABSTRACT
AT Pase family, AAA domain containing 2 (ATAD2) is a newly uncovered oncogene playing an important role in occurrence and development of prostate cancer, breast cancer and other human malignancies. It is a coactivator of a variety of transcription factors, and it can also modulate genes through epigenetic modifications, resulting in overexpression of its downstream oncogenes, and in turn changing the phenotypes of tumor cells; what's more, the expression of ATAD2 is associated with histological grade of cancer, metastasis, disease recurrence and the survival, indicating that it can be used as a molecular marker for prognosis of cancer and has remarkable value in clinical application. Furthermore, ATAD2 contains bromodomain (BRD) and also functions as cellular activity-associated ATPase, which means that ATAD2 may be a potential target for drug therapy. This review summarizes the recent findings and discusses the prospect of this field.
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<p><b>OBJECTIVE</b>To detect desialylation of platelets in primary immune thrombocytopenia(ITP) patients with FITC-labelled ECL and RCA-1, and compare the correlation of the desialylation level and the efficacy of first-line therapy for ITP.</p><p><b>METHODS</b>Before treatment, 48 ITP patients were selected and their levels of ECL and RCA-1 were detected with flow cytometry.</p><p><b>RESULTS</b>The desialylation level in the different efficacy groups by using the first-line therapy of corticosteroids and (or) intravenous immunoglobulin G (IVIG) had a statistically significant difference (P<0.05). The correlation analysis showed negative relation of the therapeutic efficacy with desialylation level, that is to say, the more high of desialylation level, the more poor therapeutic efficacy of the first-line therapy.</p><p><b>CONCLUSION</b>The desialylation level of platelets in ITP patients is related with the first-line therapeutic efficacy, the efficacy for patients with high desialylation level is poor, suggesting that the FcR-independent pathway exists in clearance of platelets in ITP patients. Therefore, the desialylation level of platelets may suggest the first-line therapeutic efficacy for ITP patients to a certain degree, and may be used as a potential target for the treatment of refractory ITP.</p>
Subject(s)
Humans , Adrenal Cortex Hormones , Blood Platelets , Flow Cytometry , Immunoglobulin G , Immunoglobulins, Intravenous , Purpura, Thrombocytopenic, IdiopathicABSTRACT
<p><b>OBJECTIVE</b>To investigate the first switched time of PML/RARα fusion gene in patients with acute promyelocytic leukemia (APL) and its clinical significance.</p><p><b>METHODS</b>sixty cases of newly diagnosed APL were enrolled in this study. They received standard remission induction, consolidation and maintenance treatments according to the clinical pathway for APL, and were followed up. During the same time the PML/RARα fusion gene mRNA expression of all cases was detected by multi-nested PCR.</p><p><b>RESULTS</b>except for 3 death cases and 1 case failed to follow-up, the PML/RARα fusion genes in the remaining 56 cases were firstly found to be negative from 24 to 381 days respectively, the mean value of the first switched time was 131 ± 90 days. There was no statistically significant difference in age, sex and risk stratification between different groups. However, the cases with L-type PML/RARα gene had shorter time compared with the patients with S-type PML/RARα gene (P = 0.032); then, for the above-mentimed 56 cases, the follow-up duration ranged from 25-1979 days (median 946 days), long-term molecular remissions had been observed in most cases, but 1 case with the first switched time of 133 days unfortunately recurred to be positive and followed by clinical relapse.</p><p><b>CONCLUSION</b>The PML/RARα fusion gene in newly diagnosed APL patients was first switched to be negative in about 4 months after treatment. The first switched time of PML/RARα fusion gene can objectively reflect the reduction of leukemia cells, and the differences among different subtypes of PML/RARα fusion gene may have some suggestions for the treatment, but without important significance for the evaluation of prognosis and recurrence for APL patients. In addition, minimal residual disease (MRD) can be dynamically monitored by detecting PML/RARα fusion gene, thus having an important clinical significance for analysis of APL recurrence.</p>
Subject(s)
Humans , Leukemia, Promyelocytic, Acute , Neoplasm, Residual , Oncogene Proteins, Fusion , Polymerase Chain Reaction , Prognosis , Recurrence , Remission InductionABSTRACT
<p><b>OBJECTIVE</b>To explore Chinese medicine (CM) syndrome distribution of chronic hepatitis B virus (HBV) carriers in immunotolerant phase (ITP).</p><p><b>METHODS</b>One hundred and eighty-five chronic HBV carriers in ITP, seen in the Third Affiliated Hospital of Sun Yat-sen University from May 2009 to December 2010, were admitted in an observational study under the guidance of CM. Patients' CM symptoms and signs, demographics, liver biochemistries, and qualitative HBV DNA were recorded in the questionnaires. CM syndromes were then differentiated to 15 detailed types and analyzed by generalization. Lastly, the location, pathogenic factors and nature of the disease were also assessed.</p><p><b>RESULTS</b>When CM syndrome patterns were differentiated to 15 types, there were 27 (15%) no syndrome cases, 94 (50%) single syndrome cases and 64 (35%) compound syndromes cases. The main detailed syndromes included Liver (Gan)-qi depression (LQD), Kidney (Shen)-qi deficiency (KQD), Spleen (Pi)-qi deficiency (SQD) and Kidney-yang deficiency (KYAD). After CM syndromes generalized to five types, their frequency was Spleen-Kidney deficiency (SKD)>LQD>inner dampness-heat retention (IDHR)>Liver-Kidney deficiency (LKD)>blood stasis blocking collateral (BSBC). SKD and LQD occupied 64%. The disease location included Liver, Gallbladder (Dan), Spleen, Stomach (Wei) and Kidney. The pathogenic factors were mainly qi stagnation, qi deficiency, yang deficiency, concurrently dampness-heat and blood stasis. The deficiency syndrome was more than excess syndrome in its nature.</p><p><b>CONCLUSIONS</b>Most of chronic HBV carriers in ITP have their CM syndrome, and the most common types are SKAD, LQD. This study suggests that the natural history may be improved through breaking the state of immune tolerance or shorten the time of ITP by strengthening Spleen-Kidney and reliving Liver qi.</p>