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Fangchinoline (FA) is an alkaloid derived from the traditional Chinese medicine Fangji. Numerous studies have shown that FA has a toxic effect on various cancer cells, but little is known about its toxic effects on germ cells, especially oocytes. In this study, we investigated the effects of FA on mouse oocyte maturation and its potential mechanisms. Our results showed that FA did not affect meiosis resumption but inhibited the first polar body extrusion. This inhibition is not due to abnormalities at the organelle level, such as chromosomes and mitochondrial, which was proved by detection of DNA damage and reactive oxygen species. Further studies revealed that FA arrested the oocyte at the metaphase I stage, and this arrest was not caused by abnormal kinetochore-microtubule attachment or spindle assembly checkpoint activation. Instead, FA inhibits the activity of anaphase-promoting complexes (APC/C), as evidenced by the inhibition of CCNB1 degeneration. The decreased activity of APC/C may be due to a reduction in CDC25B activity as indicated by the high phosphorylation level of CDC25B (Ser323). This may further enhance Maturation-Promoting Factor (MPF) activity, which plays a critical role in meiosis. In conclusion, our study suggests that the metaphase I arrest caused by FA may be due to abnormalities in MPF and APC/C activity.
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Benzylisoquinolines , Maturation-Promoting Factor , Meiosis , Mesothelin , Oocytes , Animals , Meiosis/drug effects , Oocytes/drug effects , Female , Benzylisoquinolines/pharmacology , Maturation-Promoting Factor/metabolism , Mice , cdc25 Phosphatases/metabolism , cdc25 Phosphatases/genetics , Anaphase-Promoting Complex-Cyclosome/metabolism , Mice, Inbred ICR , Reactive Oxygen Species/metabolism , DNA Damage/drug effects , Cyclin B1/metabolism , Cyclin B1/geneticsABSTRACT
Background: The aim of this study is to design a deep learning (DL) model to preoperatively predict the occurrence of central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC). Methods: This research collected preoperative ultrasound (US) images and clinical factors of 611 PTMC patients. The clinical factors were analyzed using multivariate regression. Then, a DL model based on US images and clinical factors was developed to preoperatively predict CLNM. The model's efficacy was evaluated using the receiver operating characteristic (ROC) curve, along with accuracy, sensitivity, specificity, and the F1 score. Results: The multivariate analysis indicated an independent correlation factors including age ≥55 (OR = 0.309, p < 0.001), tumor diameter (OR = 2.551, p = 0.010), macrocalcifications (OR = 1.832, p = 0.002), and capsular invasion (OR = 1.977, p = 0.005). The suggested DL model utilized US images achieved an average area under the curve (AUC) of 0.65, slightly outperforming the model that employed traditional clinical factors (AUC = 0.64). Nevertheless, the model that incorporated both of them did not enhance prediction accuracy (AUC = 0.63). Conclusions: The suggested approach offers a reference for the treatment and supervision of PTMC. Among three models used in this study, the deep model relied generally more on image modalities than the data modality of clinic records when making the predictions.
Subject(s)
Carcinoma, Papillary , Deep Learning , Thyroid Neoplasms , Humans , Lymphatic Metastasis/diagnostic imaging , Risk Factors , Thyroid Neoplasms/diagnostic imagingABSTRACT
The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family includes CMTM1-8 and CKLF, and they play key roles in the hematopoietic, immune, cardiovascular, and male reproductive systems, participating in the physiological functions, cancer, and other diseases associated with these systems. CMTM family members activate and chemoattract immune cells to affect the proliferation and invasion of tumor cells through a similar mechanism, the structural characteristics typical of chemokines and transmembrane 4 superfamily (TM4SF). In this review, we discuss each CMTM family member's chromosomal location, involved signaling pathways, expression patterns, and potential roles, and mechanisms of action in pancreatic, breast, gastric and liver cancers. Furthermore, we discuss several clinically applied tumor therapies targeted at the CMTM family, indicating that CMTM family members could be novel immune checkpoints and potential targets effective in tumor treatment.
Subject(s)
Chemokines , MARVEL Domain-Containing Proteins , Neoplasms , Humans , Chemokines/genetics , MARVEL Domain-Containing Proteins/genetics , Signal Transduction , Neoplasms/geneticsABSTRACT
Abstract@#Gurrently, healthy behaviors are the cornerstone of both physical and mental wellbeing,and more researches are focusing on improving behaviors to alleviate depression among children and adolescents. Based on the concept of 24 h movement behaviors proposed in recent years, the study examines the relationship among physical activity, sedentary behavior, sleep and depressive symptoms in children and adolescents. The research suggests that physical activity could effectively alleviate depression among children and adolescents, and its effectiveness is influenced by factors including type, intensity, duration and frequency of physical activity. Excessive sedentary behavior may increase depressive symptoms, and the impacts of different types, durations, and frequencies of sedentary behavior on depressive symptoms among children and adolescents vary. In addition to its direct impact on depression, sleep could also serve as a mediator among physical activity, sedentary behavior and depression, and there is also a crowdingout effect of time between physical activity and sedentary behavior. Future research should focus on the mechanisms and pathways underlying how 24 h movement behaviors affecting depression among children and adolescents, in order to provide more accurate solutions for the prevention and treatment of depression.
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Among the current five Variants of Concern, infections caused by the SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, architecture of intact Delta virions remains veiled. Moreover, molecular evidences for the detailed mechanism of S-mediated membrane fusion are missing. Here we reported the in situ structure and distribution of S on the authentic Delta variant, and discovered invagination in the distinctive Delta architecture. We also captured fusion snapshots from the virus-virus fusion events, provided structural evidences for Deltas attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S over that of the Wuhan-Hu-1 S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant. In BriefCryo-ET of intact SARS-CoV-2 Delta variant revealed its distinctive architecture and captured snapshots of its membrane fusion in action.
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The causative pathogen of Coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an enveloped virus assembled by a lipid envelope and multiple structural proteins. In this study, by integrating experimental data, structural modeling, and coarse-grained molecular dynamics simulations, we constructed multiscale models of SARS-CoV-2. Our 500-ns coarse-grained simulation of the intact virion allowed us to investigate the dynamic behavior of the membrane-embedded proteins and the surrounding lipid molecules in situ. Our results indicated that the membrane-embedded proteins are highly dynamic, and certain types of lipids exhibit various binding preferences to specific sites of the membrane-embedded proteins. The equilibrated virion model was transformed into atomic resolution, which provided a 3D structure for scientific demonstration and can serve as a framework for future exascale all-atom MD simulations.
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Objective:To investigate outcomes and safety of doxycycline-moxifloxacin sequential regimen in the treatment of Mycoplasma genitalium urethritis/cervicitis. Methods:From June 2019 to December 2020, patients with Mycoplasma genitalium urethritis/cervicitis confirmed by nucleic acid amplification testing were successively recruited at Department of Sexually Transmitted Diseases, Hospital of Dermatology, Chinese Academy of Medical Sciences, and received sequential therapy with oral doxycycline for 7 days followed by oral moxifloxacin for 7 days. Clinical and/or etiological assessment was conducted 2 to 3 weeks after the end of treatment. Fisher′s exact test was used to analyze factors influencing the treatment outcome. Results:Totally, 36 eligible subjects were enrolled, including 30 males and 6 females. Among them, 18 (50%) patients completed post-treatment etiological assessment, which showed that 12 achieved microbiological cure, and treatment failures occurred in 6; another 18 patients achieved clinical cure. The overall response rate to doxycycline-moxifloacin sequential therapy was 83.3% (30/36, 95% confidence interval[ CI]: 70.5%, 96.1%) . The treatment outcome showed no significant association with the patients′ age, gender, marital status, number of sexual partners in the past 1 month, history of sexually transmitted diseases, history of antibiotic use in the past 1 month, or co-infections (all P > 0.05) . Conclusion:The efficacy of doxycycline-moxifloacin sequential regimen is limited in the treatment of Mycoplasma genitalium infections in Nanjing area, and clinicians should be alerted to the possibility of treatment failure in clinical practice.
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OBJECTIVE To determi ne the contents of total fla vonoids i n Scutellaria barbata standard decoction ,evaluate in vitro antioxidant activity ,establish the fingerprint and conduct chemical pattern recognition analysis. METHODS The contents of total flavonoids in S. barbata standard decoction (calculated by scutellarein )were determined by ultraviet-visible spectrophotometry. In vitro antioxidant activity of S. barbata standard decoction was investigated by free radical scavenging tests of 1,1-diphenyl- 2-trinitrophenylhydrazine(DPPH)and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid )ammonium salt (ABTS);HPLC method was adopted. Using scutellarin as reference ,the fingerprints of 16 batches of S. barbata standard decoction were drawn and evaluated by Similarity Evaluation System of TCM Chromatogram Fingerprint (2004 A edition ),and the common peaks were determined;Pearson correlation analysis was carried out by using SPSS 24.0 software to screen substances with in vitro antioxidant activity. Taking them as variables ,cluster analysis and principal component analysis were carried out by using SPSS 24.0 and SIMCA 14.1 software. RESULTS The linear range of total flavonoids were 2.106-21.06 μg/mL(R2=0.999 3);RSDs of precision , reproducibility and stability tests (120 min)were all lower than 2%;the recovery was 100.62%(RSD=0.55%,n=6);the contents of total flavonoids were 0.634-1.053 mg/mL. Median inhibitory concentration (IC50) of DPPH radical scavenging experiment ranged 1.120-3.602 mg/mL,and IC 50 of ABTS radical scavenging e xperiment range d 0.684-1.327 mg/mL. The results of correlation analysis showed that the content of total flavonoids Δ 基金项目 :河北省高校省级重点学科建设项目 (No.冀教 in S. barbata standard decoction was negatively correlated 高〔2013〕4号);承德医学院自然科学研究计划项目(No.201824) *讲师,硕士。研究方向:中药质量控制 。电话:0314-2291186。 with the IC 50 of DPPH free radical and ABTS free radical E-mail:duyilongww@sina.com scavenging experiment ,and the correlation coefficients were # 通信作者 :教授,硕士。研究方向 :中药质量控制 。电话: -0.976 and -0.940 respectively(P<0.01). There were 18 0314-2291186。E-mail:phf2301@163.com common peaks in the fin gerprints of 16 batches of S. barbata 中国药房 2022年第33卷第4期 China Pharmacy 2022Vol. 33 No. 4 ·425· standard decoction ;the s imilarities were 0.964-0.997. A total of 4 common peaks were identified ,such as scutellarin (peak 8), scutellarein(peak 14),luteolin(peak 15),apigenin(peak 17).In the HPLC fingerprints of S. barbata standard decoction ,the peak areas of peak 3-4,8-9,12-15 and 17 were significantly negatively correlated with the IC 50 of DPPH free radical and ABTS free radical scavenging experiment (P<0.05). The results of cluster analysis showed that 16 batches of S. barbata standard decoction could be clustered into two categories ,of which S 2,S7-S8 and S 14-S16 were clustered into one category ,S1,S3-S6 and S 9-S13 were clustered into one category. By principal component analysis ,16 batches of S. barbata standard decoction were divided into two categories ,of which S 2,S4,S7 and S 14-S16 were clustered into one category ,and S 1,S3,S5-S6 and S 8-S13 were clustered into one. The comprehensive scores were high in the samples of S 4,S13,S15. CONCLUSIONS Established HPLC fingerprint and chemical pattern recognition analysis method can be used to evaluate the quality of S. barbata standard decoction ; peak 3-4,8-9,12-15 and 17 and total flavonoids are the potential material basis for S. barbata standard decoction to scavenge DPPH free radical and ABTS free radical.
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A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity between the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against infectious virus S protein. We find patterns which are conserved across all samples and this can be associated with site-specific stalling of glycan maturation which act as a highly sensitive reporter of protein structure. Molecular dynamics (MD) simulations of a fully glycosylated spike support s a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.
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Objective:To examine the infection of the enterovirus and human herpes virus in children with suspected encephalitis.Methods:A total number of 365 suspected encephalitis cases were included in this study from August 2017 to December 2019 in Hunan Children′s Hospital. The clinical samples, the cerebrospinal fluid (CSF), serum, sputum, stool and urine were collected and preserved at-80 ℃condition. The enterovirus (EV) and human herpesvirus (HHV) were examined by a one-step nested reverse transcription PCR(RT-PCR) and a real-time fluorescent quantitative PCR (qPCR), respectively. The positive rate of the two viruses in clinical specimens of children with suspected encephalitis was examined. Among all cases, 132 cases were diagnosed with EV encephalitis or HHV encephalitis.Results:the EV encephalitis were identified in 20.5% (75/365) children with suspected viral encephalitis; whereas HHV encephalitis infection was identified as 15.6% (57/365). Among the 75 cases of EV encephalitis, echo 6 was the main sub-type of these diseases 52.0% (39/75) and others were EV71 (30.7%, 23/75), echo11 (6.7%, 5/75), Coxsackie virus A group 6(CA6, 4.0%, 3/75), echo30 (1.3%, 1/75), echo9 (1.3%, 1/75), echo4 (1.3%, 1/75),Coxsackie virus B group 1(CB1, 1.3%, 1/75))and poliovirus(1.3%, 1/75).Human herpes virus type 6 (HHV6) was the most common pathogen in 57 cases of HHV encephalitis, accounting for 35.1% (20/57).The other pathogens were Cytomegalovirus (CMV, 31.6%, 18/57), Epstein-Barr virus (8.8%, 7/57), Herpes simplex virus 1 (HSV1, 10.5%, 6/57), HSV2 (8.8%, 5/57), and Varicella zoster virus (VZV, 1.8%, 1/57) .The virus in CSF detected significantly earlier than that in serum after onset. Virus could be detected in CSF 2-7 days after onset,but 7-26 days in serum. Conclusions:This study uses nested PCR and qPCR to detect pathogens in clinical specimens of children. This not only expands our understanding of the clinical examination and diagnosis of viral encephalitis in children, but also promotes the method of this study to benefit more children.
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Objective:To investigate the perfection and improvement of the execution of integrative medicine therapy in severe tetanus therapy, to successfully control tetanus severe spasms, autonomic dysfunction and prevent lethal side-effect of prolong and high-dosage sedative-muscle-relaxant therapy, resulted in significant reduction of mortality of tetanus.Methods:Symptoms, treatments and outcome of tetanus patients admitted to Peking University Third Hospital from 1965 to 2020 were reviewed. Patients were classified with Ablett classification. The cases of Ablett grade Ⅲ and Ⅳ were severe tetanus. The patients were divided into two groups according to whether they were treated together with traditional Chinese medicine (TCM) simultaneously during the standard tetanus treatment; the patients in the TCM group were divided into the tetanus TCM medication group and the non tetanus TCM medication group according to the medicine provided whether was in accord with the conventional tetanus TCM prescriptions. The mortality of each group was calculated. In addition, one survived and one deceased case with severe convulsion, autonomic nerve dysfunction (Ablett grade Ⅳ) were selected, combined with the treatment methods and curative effects, the types, use methods and outcomes of Chinese and Western medicine were analyzed.Results:The 46 tetanus cases were treated with Western medicine. Twenty-two of them, TCM were applied. Fifteen of the 22 cases took the TCM prescription which was accord with the conventional tetanus prescription. The mortality of the 46 cases was 21.7% (10/46). The number of non-TCM group was 24 cases, with mortality of 20.8% (5/24); 1 case was Ablett Ⅱ, 1 was Ablett Ⅲ and 3 were Ablett Ⅳ. The number of the TCM group was 22 cases, with mortality of 22.7% (5/22), 2 cases were Ablett Ⅲ, 3 were Ablett Ⅳ. The TCM prescription of these 5 deceased cases was not directed towards tetanus. The tetanus TCM medication group was 15 cases, with no mortality. Case analyses: case 1 was intubated because of severe spasms. Autonomic dysfunction occurred on the 8th day after admission. Esmolol with increasing the dosage of the sedatives and muscle relaxant, was not effective. Tetanus TCM was applied after 2 days of autonomic dysfunction happened. Autonomic dysfunction was then under controlled on the 2nd day post-TCM. She was recovery and discharged after 4 weeks. Case 2, also was intubated because of severe spasms. Autonomic dysfunction happened on the 3rd day after admission, and failed to be controlled by large-dose sedatives, muscle relaxant, and Esmolol. After 8 days of persistent autonomic dysfunction, tetanus TCM was applied and autonomic dysfunction was under controlled on the 2nd day post-TCM administration. Large dosage of muscle-relaxant was applied continuously. After 5 days' administration of TCM, the TCM was withdrew. One day after the withdrawal of TCM, respiratory and cardiac arrest happened because of the diffused bronchiole obstruction with pulmonary secretions loading.Conclusion:Based on the precise and real-time diagnosis of the state of the disease, integrative medicine therapy with an overall analysis tetanus TCM prescription, is the key of declining tetanus mortality.
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Objective:To understand the sleep quality and mental health status of nurses in public health emergencies, and analyze the correlation between them.Methods:A total of 128 first-line nursing staff participating in public health emergencies on February 22-23, 2020 in Tianjin Beichen Hospital, Tianjin First Central Hospital, Tianjin Fourth Central Hospital were investigated by the general data questionnaire, Pittsburgh Sleep Quality Index (PSQI), and Symptom Checklist 90 (SCL-90).Results:70.3%(90/128) of nursing staff had poor sleep quality, and the total score of PSQI was (9.71±4.01) points, which was statistically significant compared with the domestic norm ( t value was 16.479, P<0.01). The total score of SCL-90 was 1.59±0.52, which was statistically significant compared with the domestic norm ratio ( t value was 4.505, P<0.01). One-way ANOVA showed that the nursing staff's age had a significant impact on sleep quality, and the difference was statistically significant ( F value was 4.092, P<0.05). Pearson correlation analysis showed that the Pittsburgh sleep quality scale index scores and symptom self-assessment scale and somatization, force, sensitive interpersonal relationship, depression, anxiety, hostile, terrorist, paranoia, and psychosis were positively correlated( r values were 0.292-0.444, P< 0.01). Conclusions:The sleep quality and mental health status of nurses in public health emergencies are poor, and the sleep quality is correlated with mental health status.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the global pandemic of COVID-19, and no effective antiviral agents and vaccines are available. SARS-CoV-2 is classified as a biosafety level-3 (BLS-3) agent, impeding the basic research into its biology and the development of effective antivirals. Here, we developed a biosafety level-2 (BSL-2) cell culture system for production of transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). This trVLP expresses a reporter gene (GFP) replacing viral nucleocapsid gene (N), which is required for viral genome packaging and virion assembly (SARS-CoV-2-GFP/{Delta}N trVLP). The complete viral life cycle can be achieved and exclusively confined in the cells ectopically expressing SARS-CoV or SARS-CoV-2 N proteins, but not MERS-CoV N. Genetic recombination of N supplied in trans into viral genome was not detected, as evidenced by sequence analysis after one-month serial passages in the N-expressing cells. Moreover, intein-mediated protein trans-splicing approach was utilized to split the viral N gene into two independent vectors, and the ligated viral N protein could function in trans to recapitulate entire viral life cycle, further securing the biosafety of this cell culture model. Based on this BSL-2 SARS-CoV-2 cell culture model, we developed a 96-well format high throughput screening for antivirals discovery. We identified salinomycin, tubeimoside I, monensin sodium, lycorine chloride and nigericin sodium as potent antivirals against SARS-CoV-2 infection. Collectively, we developed a convenient and efficient SARS-CoV-2 reverse genetics tool to dissect the virus life cycle under a BSL-2 condition. This powerful tool should accelerate our understanding of SARS-CoV-2 biology and its antiviral development.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins and the complexes of the spike (S) proteins with the cellular receptor ACE2 or neutralizing antibodies, detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryo-electron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in both pre- and postfusion conformations were determined to average resolutions of 8.7-11 [A]. Compositions of the N-linked glycans from the native spikes were analyzed by mass-spectrometry, which revealed highly similar overall processing states of the native glycans to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNP) and its higher-order assemblies were revealed. Overall, these characterizations have revealed the architecture of the SARS-CoV-2 virus in unprecedented detail, and shed lights on how the virus packs its [~]30 kb long single-segmented RNA in the [~]80 nm diameter lumen.
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Objective:To explore the relationship between the expression level of micro RNA-133a(miR-133a) and the indexes of heart failure in patients with ischemic heart failure and its clinical application value.Methods:From January 2018 to September 2019, the clinical data of 80 patients diagnosed as ischemic heart failure in Shenyang Fourth People′s Hospital were analyzed prospectively.According to the classification of New York Heart Association(NYHA), 20 cases were divided into NYHA class Ⅰ group, class Ⅱ group, class Ⅲ group and class Ⅳ group, and 20 healthy people in the same period were selected as the healthy control group.The concentration of brain natriuretic peptide (BNP) in peripheral blood was detected by automatic immune analyzer, the indexes of cardiac function were detected by echocardiography, the expression of miR-133a in serum was detected by qRT-PCR, the difference of expression concentration of miR-133a in different functional grades was compared, and the correlation between the concentration of miR-133a and BNP and the indexes of echocardiography was analyzed.Results:The expression of miR-133a in healthy control group(0.167±0.024), NYHA Ⅰ group(0.289±0.012), NYHA Ⅱ group (0.415±0.034), NYHA Ⅲ group(0.981±0.217) and NYHA Ⅳ group(1.238±0.249) was statistically significant( F=106.4, P<0.001). Pearson correlation analysis showed that miR-133a was positively correlated with BNP in NYHAⅡ, Ⅲ and Ⅳ grade( r=0.815, 95% CI: 0.582-0.924, P<0.001; r=0.465, 95% CI: 0.029-0.753, P<0.05; r=0.749, 95% CI: 0.459-0.895, P<0.001). MiR-133 was negatively correlated with EF( r=-0.811, 95% CI: -0.875--0.719, P<0.001), positively correlated with LVPW, LV and EDV( r=0.331, 95% CI: 0.120-0.513, P<0.01; r=0.845, 95% CI: 0.764-0.896, P<0.001; r=0.705, 95% CI: 0.572-0.803, P<0.001). Conclusion:The expression of miR-133a in patients with ischemic heart failure is increased, which is related to the index of cardiac dysfunction, and has certain diagnostic and prognostic value.
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Mycoplasma genitalium can cause non-gonococcal urethritis, cervicitis, and even epididymitis, pelvic inflammatory diseases, preterm birth and other complications. Due to increased prevalence of Mycoplasma genitalium infections and emergence of resistance to a variety of commonly used antibiotics in recent years, European experts, Australian Sexual Health Alliance (ASHA) and British Association for Sexual Health and HIV (BASHH) issued guidelines for the diagnosis and treatment of Mycoplasma genitalium infections in 2016, 2017 and 2018 respectively. These guidelines provide opinions on clinical manifestations and diagnosis of Mycoplasma genitalium infections, treatment and follow-up of patients and partners, which have an important role in guiding the management of Mycoplasma genitalium infections in China.
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BACKGROUND AND OBJECTIVES: To reveal the detail mechanism of miR-484 on myocardial ischemia-reperfusion (MI/R) injury.METHODS: Rats model of MI/R injury was established based on control (Con; sham operate) group, ischemia-reperfusion (I/R) group, miR-484 treatment (miR) group, and I/R-negative control (IR-C) group, followed by pathological and interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β expression evaluation. Then the myocardial apoptosis, as well as the expression of miR-484, caspase-3, and caspase-9 in myocardium were examined. Finally, the regulatory relation between miR-484 and SMAD family member 7 (SMAD7) was predicated, followed by verification analysis.RESULTS: Compared with Con group, the expression of miR-484 in I/R and IR-C group was decreased. Compared with I/R and IR-C group, the expression of miR-484 was increased in miR group. Compared with Con group, the expression levels of IL-6, TNF-α, and IL-1β in cardiac myocytes of I/R group and IR-C group were increased. Compared with Con group, the apoptotic index, membrane potential of I/R, and the expression of caspase-3/9 were increased in IR-C group. Compared with the I/R and IR-C groups, the apoptotic index of myocardial cells in the ischemic region was decreased, the membrane potential was increased, and the expression of caspase-3/9 was decreased significantly in the miR group. SMAD7 was the target gene of miR-484.CONCLUSIONS: MiR-484 protected myocardial cells from I/R injury by suppressing caspase-3 and caspase-9 expression during cardiomyocyte apoptosis. MiR-484 reduced the expression of IL-6, TNF-α, and IL-1β in MI/R. MiR-484 might alleviate the decreasing of mitochondrial membrane potential in MI/R cells.
Subject(s)
Animals , Humans , Rats , Apoptosis , Caspase 3 , Caspase 9 , Interleukin-6 , Interleukins , Membrane Potential, Mitochondrial , Membrane Potentials , Myocardium , Myocytes, Cardiac , Reperfusion Injury , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND AND OBJECTIVES@#To reveal the detail mechanism of miR-484 on myocardial ischemia-reperfusion (MI/R) injury.@*METHODS@#Rats model of MI/R injury was established based on control (Con; sham operate) group, ischemia-reperfusion (I/R) group, miR-484 treatment (miR) group, and I/R-negative control (IR-C) group, followed by pathological and interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β expression evaluation. Then the myocardial apoptosis, as well as the expression of miR-484, caspase-3, and caspase-9 in myocardium were examined. Finally, the regulatory relation between miR-484 and SMAD family member 7 (SMAD7) was predicated, followed by verification analysis.@*RESULTS@#Compared with Con group, the expression of miR-484 in I/R and IR-C group was decreased. Compared with I/R and IR-C group, the expression of miR-484 was increased in miR group. Compared with Con group, the expression levels of IL-6, TNF-α, and IL-1β in cardiac myocytes of I/R group and IR-C group were increased. Compared with Con group, the apoptotic index, membrane potential of I/R, and the expression of caspase-3/9 were increased in IR-C group. Compared with the I/R and IR-C groups, the apoptotic index of myocardial cells in the ischemic region was decreased, the membrane potential was increased, and the expression of caspase-3/9 was decreased significantly in the miR group. SMAD7 was the target gene of miR-484.@*CONCLUSIONS@#MiR-484 protected myocardial cells from I/R injury by suppressing caspase-3 and caspase-9 expression during cardiomyocyte apoptosis. MiR-484 reduced the expression of IL-6, TNF-α, and IL-1β in MI/R. MiR-484 might alleviate the decreasing of mitochondrial membrane potential in MI/R cells.
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OBJECTIVE@#To analyze the hematological characteristics of HbE homozygotes.@*METHODS@#Complete blood cells count and hemoglobin electrophoresis were used for phenotypic analysis of 78 cases with HbE homozygotes from Yunnan province, China. The PCR-fluorescence hybridization was used to detect the common gene mutation of thalassemia. The hematological indexes, including MCV, MCH, Hb, HbA2, HbF and HbE were statistically analyzed between groups with different sex, ages and compound α thalassemia status.@*RESULTS@#In HbE homozygotes (HbEE), 89.5% (17/19) children presented mild to moderate microcytic hypochromic anemia, and 10.5% of them presented moderate anemia. 39.6% (19/48) of women with HbEE developed mild anemia ,while 11 cases of male with HbE homozygotes were asymptomatic. The levels of MCV and MCH in HbE homozygotes increased by co-inheritance of α thalassemia mutation.@*CONCLUSION@#The clinical phenotype of HbE homozygote shows highly heterogeneous, which is relates with age, sex and co-inheriting α-globin genotypes. In Hb EE women and children are more likely to develop mild to moderate anemia. The microcytic hypochromic anemia degree is relieved when HbEE combined with α- thalassemia.
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Child , Female , Humans , Male , China , Genotype , Hemoglobin E , Genetics , Homozygote , Phenotype , alpha-ThalassemiaABSTRACT
Chronic primary immune thrombocytopenia (CITP) is the most common acquired autoimmune disease that seriously threaten the physical and mental health of patients. Compared with Western medicine treatment, the intervention and treatment of Chinese medicine (CM) has shown certain therapeutic advantages. This paper reviewed the new pathogenesis progress on T cell immune abnormality in CITP, and CM studies on interferes effects of cellular immune regulation of CITP in recent years. Qi deficiency failing to control blood and internal obstruction of blood stasis are the two common types of CM syndromes in CITP patients, the corresponding treatments include invigorating Pi (Spleen), supplementing qi, activating blood, as well as tonifying qi and activating yang, regulating Gan (Liver) to invigorate Pi. The authors also mentioned the problems in the research field of CM for CTIP treatment, and put forward new ideas for the research in the future.