Objective:io investigate the expression level and clinical correlation of microRNA-144/451 gene cluster(miR-144/451)in different types of anemia.Methods:The peripheral blood of patients with aplastic anemia(AA),myelodysplastic syndrome(MDS)and diffuse large B-cell lymphoma(DLBCL)who had been diagnosed with anemia for the first time and after chemotherapy were collected.The expression levels of miR-144 and miR-451 were measured by RT-qPCR,and the correlation between the expression levels of miR-144 and miR-451 and routine laboratory indexes was analyzed by Spearman correlation analysis.Results:The expression levels of miR-144 and miR-451 in the peripheral blood of AA and MDS patients were significantly lower than those in normal controls(all P＜0.0 1).No statistical differences were observed in the expression level of miR-144 in three subgroups of DLBCL patients(P＞0.05),while the expression level of miR-451 in peripheral blood of three subgroups of DLBCL patients were significantly higher than those in normal controls(all P＜0.05).Correlation analysis showed that the expression levels of miR-144 and miR-451 in AA patients were positively correlated with red blood cell distribution width-coefficient of variation(RDW-CV)(r=0.629,0.574).There were no significant correlations between the expression levels of miR-144 and miR-451 and laboratory parameters in MDS and DLBCL patients.Conclusion:Different types of anemia disorders have varying levels of miR-144 and miR-451 expression,which is anticipated to develop into a secondary diagnostic and differential diagnostic indicator for clinical anemia diseases.

Humans ; DNA, Mitochondrial ; Cross-Sectional Studies ; East Asian People ; DNA Methylation ; Hypertension/epidemiology* ; China/epidemiology*

OBJECTIVE: To observe the effect of Biantie (bian stone plaste) pretreatment on serum level of prolyl hydroxylase domain 2 (PHD2) and hypoxia-inducible factor-1α (HIF-1α) in rats with acute hypobaric hypoxia induced-brain injury, and to explore the possible mechanism of Biantie on preventing brain injury at high altitude. METHODS: Forty-five male SD rats were randomly divided into a blank group, a model group, a Biantie group, a medication group and a Biantie+inhibitor group, 9 rats in each group. The rats in the Biantie group the and the Biantie+inhibitor group were pretreated with Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9), 2 h each time, once a day; the rats in the medication group were treated with intragastric administration of rhodiola capsule solution (280 mg/kg) for 14 d; the rats in the Biantie+inhibitor group were intraperitoneally injected with the PHD inhibitor dimethyloxalyl glycine (DMOG) at a dose of 40 mg/kg 24 h before the establishment of the model. After the intervention, except for the blank group, the rats in the remaining 4 groups were placed in the oxygen chamber to simulate a high-altitude environment to establish the acute hypobaric hypoxia brain injury model. The arterial blood-gas analysis indexes [blood oxygen saturation (SaO₂), lactic acid (Lac), blood sodium (Na⁺), blood potassium (K⁺)] and brain water content were detected in each group; the histomorphology of cerebral cortex was observed by HE staining; the serum levels of PHD2 and HIF-1α as well as vascular endothelial growth factor (VEGF) were detected by ELISA; the VEGF protein expression in brain tissue was detected by Western blot; the VEGF mRNA expression in brain tissue was detected by real-time fluorescent quantitative PCR. RESULTS: Compared with the blank group, the levels of SaO₂ and Na⁺ in the model group were decreased (P<0.05), while the levels of Lac and K⁺ as well as the water content of brain tissue were increased (P<0.05). Compared with the model group, the level of SaO₂ in the Biantie group and the medication group was increased (P<0.05), while the levels of Lac, K⁺ and the water content of brain tissue were decreased (P<0.05); the level of Na⁺ in the Biantie group was increased (P<0.05). Compared with the Biantie group, the level of SaO₂ in the Biantie+inhibitor group was decreased (P<0.05), and the level of Lac and the water content of brain tissue were increased (P<0.05). In the model group, the cortical tissue cells were loose and disordered, the cortical blood vessels were dilated, and the cells were obviously swollen; the anoxic injury in the Biantie group and the medication group was lighter, and the anoxic injury in the Biantie+inhibitor group was more obvious than that in the Biantie group. Compared with the blank group, the serum PHD2 content in the model group was decreased and the HIF-1α content was increased (P<0.05), and the content of VEGF in serum and VEGF protein and mRNA expressions in brain were increased (P<0.05). Compared with the model group, the content of PHD2 in serum in the Biantie group and the medication group was increased (P<0.05), and the level of HIF-1α was decreased (P<0.05), and the content of VEGF in serum as well as VEGF protein and mRNA expressions in brain were decreased (P<0.05). Compared with the Biantie group, the serum PHD2 content in the Biantie+inhibitor group was decreased and HIF-1α level were increased (P<0.05), and the content of VEGF in serum as well as VEGF mRNA expression in brain were increased (P<0.05). CONCLUSION Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9) could regulate serum PHD2/HIF-1α to down-regulate VEGF expression, reduce brain edema and enhance anti-hypoxia ability, so as to achieve the purpose of preventing brain injury at high altitude.
Animals ; Rats ; Male ; Prolyl Hydroxylases/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Rats, Sprague-Dawley ; Procollagen-Proline Dioxygenase/metabolism* ; Brain Injuries ; Brain/metabolism* ; RNA, Messenger ; Water

Objective: Based on the Mendelian randomization analysis, to assess the causal relationship between DNA methylation levels of Janus kinase 2 (JAK2) and obesity. Methods: A case-control study was carried out, including 1 021 individuals [obesity (visceral fat index ≥10) vs. no obesity (visceral fat index <10) was 440 vs. 581] from the Henan Rural Cohort Study. MethylTarget^TM target region methylation sequencing technology was used for testing the DNA methylation level of JAK2. logistic regression models were used to assess the association between the DNA methylation level of JAK2 and obesity. With SNP as the instrumental variable, the association between the DNA methylation level of JAK2 and obesity was explored by using the Mendelian randomization analysis method. Results: There was a positive association between Chr9:4984943 (one DNA methylation site in the promoter of JAK2) and obesity, and the OR (95%CI) was 1.22(1.04-1.42). Methylation level of five sites in the exon of JAK2 (Chr9:4985378, Chr9:4985404, Chr9:4985407, Chr9:4985409 and Chr9:4985435) were negatively associated with obesity, the corresponding OR (95%CI) were 0.53 (0.29-0.95), 0.58(0.36-0.93), 0.69 (0.49-0.97), 0.72 (0.53-0.99) and 0.58 (0.35-0.98) , respectively. Mendelian randomization analysis showed that there was a causal relationship between the DNA methylation levels of JAK2 and obesity, and the corresponding β (95%CI) were -1.985 (-3.520 - -0.450),-3.547 (-6.301 - -0.792) and -3.900 (-6.328 - -1.472) for Mendelian randomization method of inverse variance weighted, Mendelian randomization method of median based and Maximum-likelihood method, respectively. Conclusion: This study supported there was a causal relationship between the DNA methylation level of JAK2 and obesity.
Case-Control Studies ; Cohort Studies ; DNA Methylation ; Genome-Wide Association Study ; Humans ; Janus Kinase 2/genetics* ; Mendelian Randomization Analysis/methods* ; Obesity/genetics* ; Polymorphism, Single Nucleotide

To summarize YU Tian-yuan's experience of applying Danzhong (CV 17) for mental illness in acupuncture and tuina. YU Tian-yuan uses Danzhong (CV 17) alone or in combination with other acupoints to treat mental illnesses such as insomnia, palpitation and chest distress. Professor YU emphasizes 4 tips when treating diseases, nourishing the heart to tranquilize by light stimulation; regulating spirit by combined stimulation; leaving the acupoints and holding on the meridian for a wide range of stimulation; using rubbing and pushing manipulation in several directions for regulating qi to soothe the chest. And in clinical practice, formed a unique therapy to treat mental illness.
Acupuncture ; Acupuncture Points ; Acupuncture Therapy ; Humans ; Mental Disorders/therapy* ; Meridians

The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.
Animals ; Asthma/drug therapy* ; Bronchoalveolar Lavage Fluid ; Inflammation/metabolism* ; Lung ; Male ; Permeability ; Rats

Aim To investigate the mechanism by which ginsenoside Rgl regulates autophagy anrl delays brain aging in mice through AMPK/mTOR signaling pathway.Methods C57BL/6J male mice were ran¬domly divided into four groups, namely brain aging model group ,control group, Rgl anti-aging group,auto¬phagy activator Rapamycin anti-aging group.After the modeling was completed, the test of each experimental index would be carried out on the next day.Morris wa¬ter maze experiment was used to detect the learning and memory ability of mice.Paraffin sections of the hippocampus were prepared, HE , Nissl and immunohis- tochemical staining were used to observe the morpholo¬gy of hippocampal neurons, the number of neurons and Nissl bodies was counted, and autophagy-related proteins p62 , ATG5 , ULK1 were detected.Brain tissue homogenates were prepared to detect the aetivity of brain tissue acetylcholinesterase ( AChE ).Western blot was userl to detect brain tissue autophagy-related proteins LC3II, P62, beclinl, P-AMPK/AMPK, P- mTOR/mTOR and apoptosis protein P53.Results Water maze test showed that Rgl and Hap significantly improved the learning and memory abilities of brain-ag¬ing mice.HE and Nissl staining showed that Rgl and Rap decreased necrotic cells and increased the number of Nissl bodies in the hippocampus of brain-aging mice.Immunohistochemistry staining showed that Rgl and Rap decreased the expression of neuronal autoph- agv protein P62 in hippocampus and increased the ex-pression of ATG5 and ULK1.Rgl and Rap decreased the activity of AhcE in brain-aging mice.Western blot showed that Rgl and Rap increased autophagy-related proteins LC3II, Beclinl , P-AMPK/AMPK, but de¬creased the expression of P-mTOR/mTOR, P62, P53.Conclusions Ginsenoside Rgl can effectively antago¬nize the aging effect of D-gal on mouse brain.The pos¬sible mechanism is related to the regulation of autoph- agv by Rgl through AMPK/mTOR signaling pathway.

To systematically evaluate the effect of traditional Chinese medicine（TCM） on the expression of inflammatory factors in peripheral blood of patients with coronary heart disease complicated with anxiety and depression，and explore its efficacy and safety in treatment of anxiety and depression. In this study，CNKI，VIP database，WanFang database，PubMed and Cochrane Library were searched to collect randomized controlled trials（RCTs） of TCM in the treatment of coronary heart disease complicated with anxiety and depression，and 2 researchers independently screened the literatures and extracted the data. The quality of the included literatures was evaluated with Cochrance bias risk evaluation tool and Meta analysis was conducted by Cochrane Revman 5.3 software. A total of 21 research articles were included，with a total sample size of 2 342 cases，1 175 cases in the treatment group and 1 167 cases in the control group. Meta analysis results showed that the treatment group reduced the hypersensitive C-reactive protein（hs-CRP）［standard mean difference（SMD）=-1.61，95% confidence interval（CI）（-2.14，-1.09），P<0.01］，interleukin（IL）-8［mean difference（MD）=-5.03，95% CI（-8.37，-1.70），P=0.003］，IL-17［MD=-33.27，95% CI（-40.15，-26.39），P<0.01］，tumor necrosis factor（TNF）-α［SMD=-1.18，95% CI（-1.98，-0.38），P<0.01］，and homocysteine（Hcy）［MD=-3.45，95% CI（-4.85，-2.04），P<0.01］. The treatment group was better than the control group in terms of relieving anxiety and depression，i.e. scores of Hamilton anxiety scale（HAMA） ［SMD=-1.97，95% CI（-2.48，-1.46），P<0.01］，Hamilton depression scale（HAMD） ［SMD=-1.94，95% CI（-2.50，-1.38），P<0.01］，and self-rating depression scale（SDS）［SMD=-0.72，95% CI（-0.90，-0.54），P<0.01］，so in terms of ，with statistically significant difference. 4 articles mentioned that no obvious adverse reactions occurred，4 articles mentioned that the treatment group had drowsiness，dry mouth and bitter mouth，gastrointestinal reactions，but the incidence rates were significantly lower than those of the control group. The other 13 articles did not mention the occurrence of adverse reactions.

ObjectiveTo investigate the role of lncRNA-PVT1/miR-15a/ Bmi-1 pathway in the proliferation of HGC-27 gastric cancer cells in vitro. MethodsGastric cancer cell line HGC-27 was cultured in vitro and divided into the following groups： （1） blank control， si-PVT1 and si-PVT1 NC. The si-PVT1 and si-PVT1 NC groups were transferred with PVT1 siRNA and PVT1 siRNA scramble， respectively. （2） blank control， miR-15a and miR-15a NC. （3） blank control， si-Bmi-1 and si-Bmi-1 NC. Cell proliferation was evaluated by using MTS. The expression of PVT1， miR-15a and Bmi-1 was detected in the condition of PVT1 inhibition. In order to validate the relationship between miR-15a and Bmi-1， miR-15a mimic was transfected into HGC-27 gastric cancer cell line， and the expression of miR-15a and Bmi-1 was examined. The potential complementary binding sites of PVT1 and miR-15a， and miR-15a and Bmi-1 were predicted by bioinformatics. Dual-luciferase reporter assay was performed to detect luciferase activity of the different groups of cells in order to verify the relationship between PVT1 and miR-15a and miR-15a and Bmi-1. Relevant rescue experiment was conducted in order to further validate the mutual relationship of lncRNA-PVT1， miR-15a and Bmi-1. ResultsOD₄₉₀ value and cell proliferation rate were significantly decreased in the condition of PVT1 or Bmi-1 inhibition， or miR-15a overexpression （P<0.01）. The expression of Bmi-1 was decreased in si-PVT1 group， whereas miR-15a was increased （P<0.01）. miR-15a was increased after transfection， whereas the expression of Bmi-1 was decreased （P<0.01）. The dual luciferase reporter assay indicated that both the PVT1 and Bmi-1 reporter gene luciferase activity were decreased significantly in miR-15a mimics group， down-regulating 56% and 32%， respectively （P<0.01）. The expression of PVT1 and Bmi-1 was elevated in the condition of PVT1 knockdown and miR-15a inhibition， whereas both of their expression were further decreased in the condition of PVT1 knockdown and miR-15a transfection. ConclusionLncRNA-PVT1 could upregulate Bmi-1 （lncRNA-PVT1/miR-15a/Bmi-1 pathway） to promote the proliferation of gastric cancer cells in vitro by inhibiting miR-15a.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome