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In the management of obesity, aside from lifestyle interventions and surgery, pharmacotherapy is the most important choice. In recent years, research on the mechanisms of obesity and weight-loss drugs has been advancing rapidly. Exploring drugs that increase energy expenditure from the perspective of energy balance is beneficial for making clinical decisions based on the mechanisms of drugs and clinical needs in order to treat obesity effectively and improve the quality of life.
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Cellular senescence is a state in which cells enter permanent cell cycle arrest, which is characterized by senescence-associated secretory phenotype secretion, macromolecular damage, metabolic dysregulation and so on. Recent studies have shown a close relationship between cellular senescence and type 2 diabetes. On the one hand, the glycolipotoxic microenvironment of type 2 diabetes can accelerate cell senescence and accumulation. On the other hand, cellular senescence can promote the development of type 2 diabetes. For example, senescence of pancreatic β-cells leads to β-cell dysfunction and adipocytes senescence results in the secretion of pro-inflammatory cytokines, causing disturbances in lipid metabolism and exacerbating insulin resistance. Moreover, senescence of endothelial cells, retinal endothelial cells, and other cell types contributes to the occurrence of chronic complications in diabetes. Cellular senescence is not only an important factor in the onset of type 2 diabetes but also a consequence of its progression. Targeting cellular senescence holds promise as a new strategy for the treatment of type 2 diabetes.
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SARS-CoV-2 Omicron variant (B.1.1.529) was first discovered in South Africa in November 2021 and has since become a mainstream strain worldwide. Omicron variant was defined as the fifth "variant of concern (VOC)" by World Health Organization on November 26, 2021. This paper illustrates the mutation trends of Omicron variants in terms of SARS-CoV-2 genome and protein structure as well as nucleic acid site mutations and amino acid site mutations, describes the features of Omicron mutation sites in terms of lineage comparison among the VOCs and Omicron sublineages, and further highlights the influences of Omicron site mutations from the aspects of immune escape, virulence and transmission ability. Moreover, this paper also reviews the development of direct antiviral agents, antibodies and vaccines, aiming to provide reference for further investigation.
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Late-onset hypogonadism (LOH) is an age-related testosterone deficiency syndrome. With the increasing aging of society, LOH results in impaired quality of life of middle-aged and elderly men. Although domestic and international guidelines have been issued in recent years, and the management of LOH became more standardized, numerous controversies still remained in the diagnosis of LOH, the benefits of testosterone replacement therapy (TRT) and therapeutic targets. Based on comparison of different guidelines, this review focuses on age cut-off , specific signs and symptoms of LOH, diagnostic cut-off level of testosterone, the advantages and disadvantages of TRT treatment, and non-testosterone therapy.
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Objective:To compare the efficacy and safety of glucocorticoids (GCs), rituximab (RTX), and GCs combined with RTX in the treatment of active moderate-to-severe Graves′ ophthalmopathy (GO).Methods:A total of 42 patients with GO who were hospitalized in the Endocrinology Department of Jiangsu Integrated Traditional Chinese and Western Medicine Hospital from August 2017 to July 2019 were included and divided into GCs group (18 cases), RTX group (7 cases), GCs combined with RTX group (17 cases). Patients in the GCs group were received 500 mg intravenous methylprednisolone once a week for 6 weeks, followed by 250 mg intravenous methylprednisolone once a week for 6 weeks. In RTX group, patients were given intravenous RTX 100 mg every 2 weeks for 2 times. GCs combined with RTX group, i. e. RTX combined with methylprednisolone pulse therapy. At 12 and 24 weeks after treatment, CAS and NOSPECS classes were evaluated in each group. The altered course of thyroid stimulating receptor antibody were compared among the three groups. All adverse events were recorded.Results:The proportion of CAS decreased≥2 or total scores<3 points in the GCs, RTX and combined groups were 88.9%, 85.7% and 100%, with no statistical difference among the three groups ( P=0.321). At 24 weeks, CAS and NOSPECS classes decreased significantly in all three groups compared with those before treatment ( P<0.05). The reduction of CAS in the combined group was greater than in the GCs group (-3.12±1.02 vs -2.39±1.02, P=0.036) and RTX group (-3.12±1.02 vs -2.14±0.90, P=0.034). One patient in the combined group developed optic neuropathy at 24 weeks after treatment, all other patients had no severe adverse events. Conclusion:Low-dose RTX alone is not inferior to intravenous GCs in the treatment of active moderate to severe GO. GCs combined with RTX is more effective in improving patients′ CAS than either drugs alone.
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Acute respiratory distress syndrome (ARDS) is a clinical syndrome with high morbidity and mortality in the field of critical care medicine. Exploring the biological markers (groups) for early warning, severity and prognosis assessment of ARDS is the critical points of recent research. Metabolic disorders and metabolic support are drawing more and more attention in the treatment of critically ill patients. Lots of studies have shown that the changes of vitamins and their metabolites can dynamically correspond to the damage of ARDS, which might be the biomarker for early diagnosis, dynamic evaluation, and specific treatment of ARDS. Vitamin metabolomics, as an important branch of metabolomics, can better help us find the potential biomarkers for ARDS. Metabolomics is the latest technology of precision medicine. The use of metabolomics to analyze vitamin metabolites and their pathways is of great significance in the diagnosis, treatment and monitoring of critical illnesses. This article reviews the research progress of vitamin metabolomics in ARDS.
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Objective To investigate the outcome and affecting factors of patients with osteosarcoma after recurrence.Methods Retrospective analysis was used to analyze the achieved data and prognosis-related factors of 72 patients with extremity osteosarcoma after recurrence from June 2000 to September 2012 through multicenter joint treatment.37 males and 35 females were included.The overall age was 7 to 61 years old (average age22.2 years old).Classification based on the tumor recurrent parts:42 cases (58.3%) on femur,18 cases (25%) on tibia,7 cases (9.7%) on humerus and 5 cases (6.9%) on fibula.Classification based on metastases:14 cases of simple recurrence (19.4%),58 cases (80.6%) of recurrence with metastasis:29 cases (40.3%) of recurrence occurred first,9 cases (12.5%) of metastasis occurred firstly,20 cases (27.8%) of simultaneous recurrence with metastasis;12/14 patients (16.7%) of simple recurrence had long-term survival,but 2 died (2.8%).Six of 58 patients (8.3%) of recurrence with metastasis had long-term survival but 52 died (72.2%).Results The overall 10-year postrelapse survival rate of the 72 patients was 25%.Kaplan-Meier univariate analysis revealed that postrelapse survival was significantly influenced by the continued treatment after recurrence and the number of postoperative chemotherapy,but it was not significantlyinfluenced by age,gender and the number of preoperative chemotherapy.Multivariate analysis revealed that the continued treatment after recurrence and the number of postoperative chemotherapy were independent prognostic factors (P=0.002,P=0.007).At the same time,according to the survival curve grouped by different indicators,the number of chemotherapy after recurrence has no significant effect on TFS.However,the continued treatment after recurrence has obvious statistical significance on improving TFS and OS of patients (P=0.026,P=0.002).Conclusion Resection and standard postoperative chemotherapy had significant effects on the postrelapse survival in patients with osteosarcoma.There are good prospects for further multimodal therapy and multicenter cooperation for osteosarcoma after recurrence.
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Objective:To establish the quality standard for Xiaotang Zhike pills.Methods:Atractylodis Rhizoma,Puerariae Lobatae Radix and Scrophulariae Radix in the formula were qualitatively identified by TLC. HPLC was used for the determination of puerarin in Xiaotang Zhike pills. The analysis was performed on a Wondasil C18-WR(250mm × 4.6 mm,5 μm)column with methanol-water(25:75) as the mobile phase at a flow rate of 1.0 ml·min-1. The detection wavelength was set at 250 nm, the column temperature was 40℃ and the sample size was 10 μl. Results:TLC showed good specificity without any interference for the identification of atrctylodin,puerarin and harpagoside. The calibration curve of puerarin was in good linearity over the range of 41.20-618.00 ng(r = 0.999 9). The average recovery was 100.16%(RSD = 2.91%). Conclusion:The established methods in the study are simple,feasible and reproducible,which are suitable for the quality control of Xiaotang Zhike pills.
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Objective Abnormal activation of mitogen-and stress-activated kinase (MSK1) plays an important role in the development of various cancers.This study was to explore the effect of small interfering RNA (siRNA)-mediated MSK1-silencing on the proliferation of human nasopharyngeal carcinoma (NPC) cells and its underlying mechanism.Methods The siRNA vector targeting MSK1 was constructed and transfected into CNE2 cells, and the NPC cell line stably expressing MSK1 was established.Then the cells were divided into a blank control (without transfection of the plasmid), a negative control (with stable transfection of the negative control plasmid), and an experimental group (with stable transfection of the positive recombinant plasmid).The expressions of MSK1 mRNA and protein were detected by real-time quantitative PCR and Western blot, respectively, the proliferation of the cells determined by CCK-8 and colony formation assays, the cell cycles analyzed by flow cytometry, the level of histone H3 phosphorylation at Ser10 examined by Western blot, and The transcriptional activity and expression of the c-jun protein measured by dual-luciferase reporter gene assay and Western blot.Results Compared with the blank control, the inhibition rates of cell proliferation at 48, 72 and 96 hours were significantly reduced in the experimental group (P<0.05), and so were the colony formation ability of the cells (P<0.01) and the expression and transcriptional activity of the c-jun protein (P<0.05).In comparison with the negative control, the experimental group showed significant decreases in the rate of cell growth after 24 hours, the inhibition rates of cell proliferation at 48, 72 and 96 hours (P<0.05), the number of formed colonies ([221.00±20.08] vs [99.67±15.57] / 300 cells, P<0.01), the proportion of S-phase cells (P<0.01), and the expression of the c-jun protein in the CNE2 cells ([100.00±0.00] vs [48.77±10.71] %, P<0.05), but a remarkable increase in the percentage of G0/G1-phase cells (P<0.01).Furthermore, histone H3 phosphorylation at Ser10 was markedly reduced (P<0.01) but no significant change was observed in the expression of the total c-jun protein in the experimental group.Conclusion Knockdown of MSK1 using siRNA can significantly inhibit the growth and proliferation of CNE2 cells, which may be closely related to the decreased phosphorylation of histone H3 and subsequently down-regulated transcriptional activity of c-jun.
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To evaluate the expression of cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1α) in non-small cell lung cancer (NSCLC) and its correlation with clinicopathological features. Methods: PRKAR1α expressions in 79 NSCLC patients and matched adjacent non-carcinoma tissues were analyzed by using qRT-PCR and immunohistochemistry. Results: The negative rates of PRKAR1α protein in NSCLC, lung squamous cell carcinoma (SCL) and lung adenocarcinoma (ACL) were 58.2%, 77.8%, 32.4%, respectively. Compared to the matched adjacent non-carcinoma tissues, there were significant differences in levels of PRKAR1α mRNA and protein in ACL (P0.05). The expression of PRKAR1α protein was positively correlated with histological type, TNM stage, and lymph node metastasis (P0.05). Conclusion: Low expression of PRKAR1α in ACL might be involved in the pathogenesis, which might serve as a novel diagnostic candidate.
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Female , Humans , Male , Adenocarcinoma , Chemistry , Classification , Genetics , Adenocarcinoma of Lung , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung , Chemistry , Genetics , Carcinoma, Squamous Cell , Chemistry , Genetics , Cyclic AMP-Dependent Protein Kinase RIalpha Subunit , Physiology , Gene Expression Profiling , Immunohistochemistry , Lung Neoplasms , Chemistry , Classification , Genetics , Lymphatic Metastasis , Genetics , Neoplasm Staging , RNA, MessengerABSTRACT
@#The characteristics of patients with spinal cord injury are shown as: disorder of the lung function and gas exchange, influence of body position, maximum inspiratory and expiratory pressure decreased, cough, airway obstruction, ect. The management of lung function currently include exercise, pacing therapy and medicine.
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The characteristics of patients with spinal cord injury are shown as:disorder of the lung function and gas exchange, influ-ence of body position, maximum inspiratory and expiratory pressure decreased, cough, airway obstruction, ect. The management of lung function currently include exercise, pacing therapy and medicine.
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OBJECTIVE@#To evaluate the influence of perioperative intravenous administration of ambroxol on pulmonary function, postoperative complications, postoperative hospital stay, and cost after video-assisted thoracic surgery lobectomy for lung cancer.@*METHODS@#Sixty patients who underwent video-assisted thoracic surgery lobectomy for lung cancer in Xiangya Hospital, Central South University between May 2011 and May 2012 were randomly assigned into 2 groups: An ambroxol group (n=30) and a control group (n=30). In the ambroxol group, patients were given ambroxol (1 000 mg/d) on the day of operation and on the first 3 postoperative days. In control group, placebo was given. The pulmonary function tests, arterial blood gases, incidence of perioperative morbidity, postoperative mechanical ventilation time, duration of ICU stay, length and costs of postoperative hospital stay were compared between the 2 groups.@*RESULTS@#The 2 groups were well matched for demographics and operative variables. The ambroxol group showed better the percent predicted forced expiratory volume in 1 second (FEV1%), the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC%), the percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) and arterial oxygen pressure than the control group. The postoperative pulmonary complications was significantly reduced, the duration of mechanical ventilation and the length of ICU stay were shortened, and the length and costs of postoperative hospital stay were significantly decreased in the ambroxol group compared with the control group (all P<0.05).@*CONCLUSION@#Perioperative intravenous administration of ambroxol can improve the postoperative lung function, reduce the incidence of pulmonary complications, shorten the length of postoperative hospital stay, and lower the total cost of hospitalization after video-assisted thoracic surgery lobectomy for lung cancer.
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Humans , Ambroxol , Therapeutic Uses , Length of Stay , Lung , Lung Neoplasms , General Surgery , Oxygen , Perioperative Period , Postoperative Complications , Respiratory Function Tests , Thoracic Surgery, Video-Assisted , Tidal Volume , Vital CapacityABSTRACT
Objective To investigate the impacts of carvedilol combined with pravastatin,on aminoterminal pro-brain natriuretic peptide(NT-proNBP),cardiac troponin Ⅰ(cTnI)and cardiac function in coronary heart disease patients with chronic heart failure.Methods One hundred and tewnty five cases of coronary heart disease patients with chronic heart failure were randomly divided into the carvedilol group(63 cases)and carvedilol combined with pravastatin group(62 cases).In addition to using certain dosage of the above-mentioned drugs respectively,both groups underwent routine anti heart failure treatment with the course of 12 weeks.The class of heart function and changes of heart rate(HR) were observed before and after treatment.Left ventricular end diastolic diameter(LVEDD),left ventricular end systolic diameter(LVESD) and left ventricular ejection fraction(LVEF) were determined by using ultrasound heartbeat graph.Six min walk test(6MWT)was also observed before and after treatment and the level of NT-proBNP and cTnI level were determined by using an enzyme immunoassay method.And patients readmission rates and the incidence of cardiovascular events were also observed.Results The condition of carvedilol and pravastatin group were improved after treatment compared with before treatment[HR:(78±12) CICCS/min vs(100±112) CICCS/min,t =13.682,P < 0.05 ;LVEDD:(43±5)mmvs(53±8)mm,t=5.284,P<0.01;LVESD:(42±6)mmvs(56±7)mm,t=6.454,P<0.01;LVEF:(50±5)% and(35±8)%,t=-6.091,P<0.01);NT-proBNp:(986±713)ng/Lvs (3328±1109) ng/L,t =17.626,P < 0.05) ; CInI:(0.85±0.16) μg/L vs(2.03±0.63) μg,/L,t =5.879,P < 0.01 ;6MWT:(355.6±92.5)m vs(238.8±101.4) m,t =-8.255,P < 0.01].After 3 months follow-up,the condition of carvedilol combined with pravastatin group were better than carvedilol group;LVEDD:(43±5)mm vs(57±6)mm,t =5.892,P <0.05 ;LVESD:(42±6)mm vs(49±7) mm.t =3.243,P <0.01 ;LVEF:(50±5) % vs(42±8) %,t =-12.036,P < 0.01 ; NT-proBNP:(986±713) ng/L vs(1626±968) ng/L,t =3.603,P <0.01 ;cTnI:(0.85±0.16) μg/L vs(1.15±0.36) μg/L,t =3.200,P < 0.01 ;6MWT:(355.6±92.5) mvs(296.2±99.5) m,t =-10.119,P < 0.01].The rehospitalization rate(3.3 % vs 12.7%,x2 =6.224,P < 0.05) and the incidence of cardiovascularevents(3.3% vs 15.9%,x2 =5.974,P < 0.05) were both decreased Significantly after treated with carvedilol combined with pravastatin.Conclusion Carvedilol combined with pravastatin can reduce the level of NT-proBNP and cTnI,improve heart function in coronary heart disease patients with chronic heart failure.
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According to teaching practice,the authors discuss the problems on teaching exploratory experiment of experimental physiology sciences and propose some reflection and suggestions.
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Site-directed mutagenesis method was used to introduce two desired mutations, which were confirmed by DNA sequencing, into mouse complement receptor Type II gene(MCR2). Then the constructed eukaryotic expression vectors containing wild type mouse CR2/1(wtMCR2/1), mutant type mouse CR2/1 (mtMCR2/1) and human CR2 (hCR2) cDNA were transferred into mouse SP2/0 cells by electroporation. After two-week screening by G418, the stably transfected clones were obtained. Several ways including PCR, RT-PCR, and immunohistochemistry were utilized to screen those clones with interesting genes integrated and expressed. Then Epstein-Barr virus(EBV) was used to infect these transfected cells and EBER-1 (EBV encoded RNAs) hybridization results showed that only hCR2 and mtMCR2 transfected SP2/0 cells could be infected by EBV, but positive rate of the former was much higher than the latter. This study sets groundwork for elucidating the mechanism by which EBV enters the cells and for establishing the animal model of EBV-related nasopharyngeal carcinoma (NPC).
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The effects of antisense oligonucleotides of c-fos and c-jun on the proliferation of CNE-2Z cells and on the expression of protein kinase C-? (PKC-?) were investigated. With the interpoising of Lipofectin(LP), the CNE-2Z cells were added with antisens oligonucleotides of c-fos and c-jun. MTT method was used to test the cell proliferation and flow cytometry (FCM) to the PKC-a expression. The results showed that the inhibition of antisense oligonucleotides of c-fos and c-jun to CEN-2Z cells was gradually enhanced with its concentration and prolonging time increasing and that its lowest effective concentration of LP was 1.7 X 10~(-6)?g/ml, the lowest effective concentration was of antisense oligonucleotides of c-fos and c-jun 1.7 x 10~(-5)?g/ml, and the most effective time was 20 hours after treatment. The fluoresence of PKC-a and percentage of positive cells in the groups treated by antisense oligonucleotides of c-fos and c-jun decreased significantly. The results indicated that the autisense oligonucleotides of c-fos and c-jun could inhibit the proliferation of CNE-2Z ceUs the expression of PKC-?.
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Persisting the comprehensive,persistent developing value of man-oriented is a key strategic thought guided by Deng Xiaoping theory and the key thought of "Three Representatives" starting from the general development of our party and our country in the new century.The environment ethics and the persistent development are coherent in the spiritual essence.Their tenet lies in the solution of environmental crisis,the coherent relationships of human beings and nature,the guarantee of the persistent development on the better basis of nature.In implementing the strategy of persistent development the social function of the environmental ethics is its function of adjustment and standardization;its guiding function to the practical activities of human beings protecting environment;its criticizing function;its function of education and encouragement;the indispensible basic function of environmental ethics to the environmental legislation.
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AIM: To establish nasopharyngeal carcinoma(NPC) cell lines stable expressing NPC-derived latent membrane protein 1(LMP1) gene. METHODS: General expression vector and epithelium-specific expression vector of NPC-derived LMP1 gene were constructed by using recombinant techniques, then transfected these vectors into a poor differentiated NPC cell line named CNE-2 ,integration and expression of N-LMP1 in CNE-2 cells were detected by PCR,RT-PCR and Western blot. RESULTS: (1) General expression vector and epithelium-specific expression vector of NPC-derived LMP1 gene were constructed successfully.(2) It showed that N-LMP1 gene expressed in CNE-2 cells correctly. CONCLUSION: The first NPC cell lines which stable express NPC-LMP1 were established. The cell lines obtained will provide important basis for exploring the role of NPC-LMP1 in nasopharynx carcinogenesis.