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@#Objective To study the effect of Tangeretin on non-small cell lung cancer (NSCLC) and the tumor stemness, and to find the molecular mechanism of its effect. Methods We used cell counting and cell cloning experiments to study the effect of Tangeretin on the proliferation of NSCLC cells in vitro. The effect of Tangeretin on the invasion of NSCLC cells was detected by transwell assay. We detected the effect of Tangeretin on the proliferation of NSCLC cells in vivo by nude mouse tumor-bearing experiment. The effect of Tangeretin on tumor stemness of NSCLC cells was detected by self-renew assay, and CD133 and Nanog protein expressions. The expressions of PI3K/AKT/mTOR signaling pathway-related proteins were detected by Western blotting (WB). Results Tangeretin had a good inhibitory effect on the proliferation of NSCLC cells in vivo and in vitro. Cell counting experiment, clonal formation experiment and nude mouse tumor-bearing experiment showed that Tangeretin could inhibit the proliferation activity, clonal formation ability, and tumor size of NSCLC cells in vivo. Self-renew experiments showed that Tangeretin could inhibit the self-renew ability of NSCLC cells. WB experiments showed that Tangeretin inhibited the expressions of tumor stemness markers CD133 and Nanog in NSCLC cells. Tangeretin could inhibit the activation of PI3K/AKT/mTOR signaling pathway-related proteins in NSCLC cells, and the activation of PI3K/AKT/mTOR signaling pathway could partially remit the inhibitory effect of Tangeretin on tumor stemness of NSCLC cells. Conclusion Tangeretin can inhibit the tumor stemness of NSCLC cells, which may be related to the regulation of PI3K/AKT/mTOR signaling pathway.
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Autoimmune diseases of the nervous system are a group of diseases caused by the body′s immune system attacking its own nervous system, resulting in structural damage and functional impairment of the corresponding tissues. Interventional clearance of pathogenic auto-antibodies has been shown to be effective in reducing immune damage, inhibiting disease progression and improving prognosis through extensive basic research and long-term clinical practice. The neonatal Fc receptor (FcRn)-mediated circulating protection mechanism of IgG contributes to the long half-life and high plasma levels of IgG. FcRn inhibitors are able to target and block the binding of FcRn to IgG, accelerating IgG clearance and reducing IgG levels. Therefore, the use of FcRn inhibitors in the treatment of autoimmune diseases of the nervous system could theoretically help to accelerate the clearance of pathogenic IgG, achieve good clinical efficacy and have promising applications. Research in this area has made considerable progress in recent years and this article will review this.
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Cystitis， one of the most common diseases in the urinary system， is manifested by urinary frequency， urinary urgency， and bladder pain， which are known as the classic symptom triad of bladder irritation， especially in women. In recent years， with the change of the lifestyle， the prevalence of bladder diseases in China is increasing year by year. According to the characteristics of etiology， pathogenesis， and clinical symptoms of cystitis， this paper listed the clinical diagnostic criteria in traditional Chinese medicine （TCM） and western medicine after consulting the relevant literature. Through the analysis of the existing animal model of cystitis， the fit between the model and clinical manifestations was evaluated， and the advantages and disadvantages were summarized. The models induced by "intraperitoneal injection of cyclophosphamide" and "Freund's complete adjuvant combined with bladder catheterization" were proved highly matched with manifestations despite some shortcomings such as long time and high cost. At present， the diagnostic criteria of cystitis are mainly based on western medicine， and the definitive diagnosis of the relevant types still depends on cystoscopy and tissue biopsy. The lack of TCM syndrome model limits the TCM research. Additionally， four diagnostic methods in TCM cannot be well applied to animal models because of the susceptibility to subjective factors. Behavioral tests can be used to determine the model index and develop the relevant behavior rating scale. Therefore， it is necessary to establish an animal model of cystitis in line with the clinical characteristics of western medicine and TCM syndrome differentiation， so as to better promote the study of cystitis.
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This paper collated the western medicine and traditional Chinese medicine （TCM） diagnostic criteria of pulmonary fibrosis （PF） based on its clinical characteristics and relevant literature reports and summarized the inductive agents， methods， objects， and mechanisms for replicating the PF animal models as well as their respective advantages and disadvantages. By analyzing the consistency of symptoms among successfully modeled animal models with the clinical characteristics in TCM and western medicine， we found that the intratracheal injection of bleomycin was the most frequently employed method for modeling， and the resulting outcomes were very similar to clinical characteristics in TCM and Western Medicine. Besides， considering the time-saving process， high stability， good repeatability， and low cost， such method was suitable for the rapid screening of drugs. The second preferred method was intraperitoneal injection of paraquat， which exhibited the advantages of high degree of consistency with clinical characteristics of PF caused by paraquat poisoning， low cost， high success rate， and easy operation， which allowed it to be suitable for exploring the mechanism of paraquat poisoning and developing the antidotes. The existing PF animal models shared a fairly high degree of consistency in symptoms with patients diagnosed as having PF in western medicine. However， the criteria for TCM syndrome differentiation remained unclear， and the animal models failed to reflect TCM pathogenesis. It is necessary to establish more accurate TCM diagnostic criteria that focus on syndrome differentiation and reveal TCM etiology and pathogenesis and carry out more experiments concerning TCM syndromes of PF in the future， so as to better treat PF with integrated TCM and Western Medicine.
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Based on the clinical characteristics of thromboembolic vasculitis， the diagnostic criteria in western medicine and the dialectical standard in traditional Chinese medicine （TCM） were analyzed and established by consulting relevant literature， and the modeling method， modeling objects as well as modeling advantages and disadvantages for the animal models of thromboembolic vasculitis were summarized in this paper. By analyzing its coincidence with the characteristics of clinical symptoms in traditional Chinese and western medicine， it was found that the animal model of thromboembolic vasculitis had a higher degree of coincidence with the clinical symptoms in western medicine， as well as cold and dampness blocking collaterals syndrome and heat toxin injury yin syndrome in TCM， but lower degree of coincidence with damp-heat toxin syndrome and Qi-blood deficiency syndrome. There is no animal model consistent with blood stasis syndrome. The pathological and hemorheological indexes （blood viscosity， erythrocyte sedimentation rate） were the most common indexes. Compared with a large number of cases reported in clinical treatment of thromboangiitis obliterans， the experimental research was relatively weak. It is the focus of future research to establish a reasonable model to judge the quantitative standard， and to establish the animal model with higher coincidence degree with TCM syndrome.
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Based on the characteristics of clinical symptoms of secretory otitis media in traditional Chinese and Western medicine,by reference to clinical diagnostic criteria,efforts were made to analyze and establish the Western medical diagnostic criteria and traditional Chinese medicine( TCM) syndrome differentiation criteria for secretory otitis media,and summarize the modeling methods and model characteristics of secretory otitis media animal models. According to the clinical diagnostic criteria and symptom characteristics,the coincidence degree between the existing animal models and clinical symptoms was evaluated,and its advantages and disadvantages were defined. On the basis of the statistical results,there were fewer methods for modeling secretory otitis media animal models,and only a specific relevant pathogenic mechanism could be revealed. Among them,the model with a higher coincidence degree was genetic engineering technology modeling and injection into the middle ear vesicles. The two modeling methods of bacterial factors highly coincided with the clinical symptoms of Western medicine,but both failed to reflect the TCM syndrome type. Therefore,establishing an animal model that simultaneously reflects the characteristics of clinical symptoms of secretory otitis media in traditional Chinese and Western medicine,and improving the evaluation criteria of secretory otitis media based on animal models are the main tasks of future studies on secretory otitis media.
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Animals , China , Disease Models, Animal , Medicine , Medicine, Chinese Traditional , Otitis Media with Effusion/drug therapyABSTRACT
Objective@#To identify and analyze the variants of the KCNJ1 gene in five Chinese patients with Bartter syndrome type 2 (BS2), and to describe their clinical features as well as treatment results.@*Methods@#Data and blood samples of five BS2 patients and their relatives confirmed by Qingdao Municipal Hospital from June 2012 to January 2019 were collected. Whole-exome-sequencing (WES) based on the second generation high throughput sequencing was performed to detect variants. The 2015 American College of Medical Genetics and Genomics Standards and Guidelines were applied to analyze the pathogenicity of the variants. The clinical features and laboratory results were retrospectively studied. The response to treatment and follow-up data were reviewed.@*Results@#Ten variants including six novel ones of KCNJ1 gene were identified through WES and verified by Sanger dideoxy sequencing. Missense variants accounted for the highest proportion. The common symptoms and signs of five BS2 patients from high to low incidence were polydipsia and polyuria (5/5), one of them (1/5) presented with diabetes insipidus; maternal polyhydramnios and premature delivery (4/5); growth retardation (3/5). Initially, two patients presented with hypochloremic metabolic alkalosis and hypokalemia, whereas the acid-base disturbance was absent in the others. One patient experienced hyperkalemia. In terms of calcium-phosphorus metabolism, one patient had evident parathyroid hormone (PTH) resistance (hypocalcemia, hyperphosphatemia and markedly elevated serum intact PTH levels), three presented with PTH overacting (hypercalcemia, hypophosphatemia and mild elevated serum intact PTH levels), and one showed normal blood calcium and phosphorus concentrations with high-normal serum intact PTH levels. All patients had nephrocalcinosis or hypercalciuria, and one of them complicated with nephrolithiasis. Indomethacin helped to correct the growth retardation, halt polydipsia polyuria, decrease the elevated urinary calcium excretion, and normalize electrolyte disturbance as well as PTH parameters in some patients.@*Conclusions@#This investigation identifies ten variants of KCNJ1 gene, including six ones that have not been previously reported, which will enrich the human gene mutation database (HGMD). These patients in our study have atypical BS phenotype, so that careful differentiation from other parathyroid diseases will be required for clinicians.
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Objective:To identify and analyze the variants of the KCNJ1 gene in five Chinese patients with Bartter syndrome type 2 (BS2), and to describe their clinical features as well as treatment results. Methods:Data and blood samples of five BS2 patients and their relatives confirmed by Qingdao Municipal Hospital from June 2012 to January 2019 were collected. Whole-exome-sequencing (WES) based on the second generation high throughput sequencing was performed to detect variants. The 2015 American College of Medical Genetics and Genomics Standards and Guidelines were applied to analyze the pathogenicity of the variants. The clinical features and laboratory results were retrospectively studied. The response to treatment and follow-up data were reviewed.Results:Ten variants including six novel ones of KCNJ1 gene were identified through WES and verified by Sanger dideoxy sequencing. Missense variants accounted for the highest proportion. The common symptoms and signs of five BS2 patients from high to low incidence were polydipsia and polyuria (5/5), one of them (1/5) presented with diabetes insipidus; maternal polyhydramnios and premature delivery (4/5); growth retardation (3/5). Initially, two patients presented with hypochloremic metabolic alkalosis and hypokalemia, whereas the acid-base disturbance was absent in the others. One patient experienced hyperkalemia. In terms of calcium-phosphorus metabolism, one patient had evident parathyroid hormone (PTH) resistance (hypocalcemia, hyperphosphatemia and markedly elevated serum intact PTH levels), three presented with PTH overacting (hypercalcemia, hypophosphatemia and mild elevated serum intact PTH levels), and one showed normal blood calcium and phosphorus concentrations with high-normal serum intact PTH levels. All patients had nephrocalcinosis or hypercalciuria, and one of them complicated with nephrolithiasis. Indomethacin helped to correct the growth retardation, halt polydipsia polyuria, decrease the elevated urinary calcium excretion, and normalize electrolyte disturbance as well as PTH parameters in some patients. Conclusions:This investigation identifies ten variants of KCNJ1 gene, including six ones that have not been previously reported, which will enrich the human gene mutation database (HGMD). These patients in our study have atypical BS phenotype, so that careful differentiation from other parathyroid diseases will be required for clinicians.
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OBJECTIVES@#To explore the relevant protective and risk factors that affect spontaneous supratentorial large volume intracerebral hemorrhage.@*METHODS@#Clinical data of hospitalized patients with spontaneous supratentorial intracerebral hemorrhage in Xiangya Hospital of Central South University from January 2014 to December 2018 were retrospectively analyzed. According to the amount of intracerebral hemorrhage (≥30 mL), the patients were divided into a large volume intracerebral hemorrhage group (255 cases) and a non-large volume intracerebral hemorrhage group (397 cases). Univariate and multivariate logistic regression analysis for the clinical data from the two groups of patients were performed.@*RESULTS@#Systolic blood pressure, diastolic blood pressure, white blood cell count, neutrophil count, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, calcium ion concentration, and international standard ratio between the large volume intracerebral hemorrhage group and the non-large volume intracerebral hemorrhage group were significantly different (all @*CONCLUSIONS@#The occurrence of spontaneous supratentorial large volume intracerebral hemorrhage is the result of combination of multiple factors. The increased white blood cell count, the increased systolic blood pressure, the increased high-density lipoprotein cholesterol, and the increased international standard ratio may increase its risk, while the increased LDL cholesterol and calcium concentration may reduce its risk.
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Humans , Blood Pressure , Cerebral Hemorrhage , Cholesterol, HDL , Retrospective Studies , Risk FactorsABSTRACT
Circular RNA (circRNA) is a non-coding closed-loop single-stranded RNA molecule lacking the 5' end cap and the 3' poly (A) tail. Circular RNA is more abundant and stable than linear mRNA, and its expression is more conservative and specific. circRNA regulates cancer development through a variety of mechanisms, including miRNA sponges, regulating gene transcription, regulating RNA-binding proteins, and protein translation. This review summarizes the role of circRNA in cancer and helps to develop new clinical diagnostic techniques and treatments.
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Due to the potent bactericidal activity and low incidence of drug resistance, the novel cyclic lipopeptide antibiotic - daptomycin has emerged as one of the first line antimicrobial agents in the treatment of serious infections caused by gram-positive resistant pathogens. This review summarizes the research advances of daptomycin in recent years, mainly including spectrum of antimicrobial activity, biosynthesis, mode of action, mechanism of drug resistance, structure-activity relationships, surotomycin and siderophore-daptomycin conjugate to kill multidrug resistant Acinetobacter baumannii. The findings summarized in this review highlight the directions of next-generation of daptomycin derivatives.
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Epsilon 3xenergy dispersive X-ray fluorescence spectrometer (EDXRF) was used to analyze the major and minor elements in marine sediments collected from the Indian Ocean on-site. Results obtained by EDXRF were compared with those by inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-optical emission spectrometry (ICP-OES) in the laboratory A total of 24 elements in marine sediment samples,namely Al2O3,MgO,Fe2O3,Na2O,K2O,CaO,Mn,P,Ti,Ba,Sr,V,Zn, Zr, Co,Ni,Cu,Ga,Rb,Y,Nb,Mo,Nd,Pb and Th were measured,and a good agreement was found for these elements(R2>0.9),except for Al2O3,and Ga,Nb and Th with content lower than 30 μg/g. The mean relative deviations of EDXRF method were less than 10% for all of the above mentioned major elements, except for MgO in low concentration and P in high concentration. The mean relative deviations were less than 25% for all of the above mentioned trace elements,except for Sr(>700 μg/g),Mo(<20 μg/g) and Nb. In general, precision and accuracy of EDXRF method were good enough for detection of marine sediments. Taking into account all these facts, the EDXRF method proposed here was proved to be an effective tool for element determination in marine sediment on-site,and it would provide a new technical support to investigate the spatial distribution of mineral resources in marine geological survey.
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Objective To analyze and identify the mutations in SGLT2 gene of nine Chinese families with FRG, and determine the renal threshold for glucose excretion (RTG), so as to explore the association of genotype and RTG. Methods All coding regions of SGLT2 gene, including intron exon boundaries, were analyzed using PCR followed by direct sequence analysis. Quantitative test for 24?hour urine glucose and RTG were measured among 9 probands (21 patients) and their family members from 9 pedigrees (total 25 subjects). The differences in renal glucose thresholds between patients with different genotypes (heterozygotes and compound heterozygotes; c.886(-10_-31) del heterozygotes and other heterozygotes) were compared. Results Twelve mutations were identified by SGLT2 gene analysis, including 10 novel ones that were not included in HGMD:c.331T>C, p.W111R;c.374T>C, p.M125T; c.394C>T, p.R132C; c.612G>C, p.Q204H; c.829C>T, p.P277S; c.880G>A, p.D294N;c.1129G>A, p.G377S; c.1194C>A, p.F398L; c.1540C>T, p.P514S; c.1573C>T, p.H525Y. In thisstudy, the mutation c.886(-10_-31)del that is specific to Chinese population accounted for about 28％of the total alleles (5/18). The RTG values of patients with compound heterozygous mutations were much lower than those with simple heterozygous mutations [(1.28 ±0.10) vs (5.14±0.77) mmol/L; P<0.001];and c.886(-10_-31)del heterozygotes had significant lower RTG values than others [(4.43 ± 0.37) vs (5.70 ± 0.51) mmol/L, P<0.001]. Conclusions Ten novel mutations which may be related to FRG are found in this study, and c.886(-10-31)del may be a hot?spot mutation in Chinese patients. Compound heterozygotes had much lower RTG values than simple heterozygotes.
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Objective To analyze the mutations of SLC12A1 gene in nine Chinese families with Bartter syndrome type I (BS1),and analyze the relationship between genotype and phenotype.Methods The next generation sequencing was used to detect mutations in nine BS1 patients including eight with antenatal BS (aBS) and one with classical BS (cBS).Clinical characteristics and biochemical findings at the first admission as well as follow-up were reviewed.Results 15 different mutations of SLC12A1 gene were identified,including 11 novel ones.Among nine probands,seven were compound heterozygotes,two were homozygotes.All patients presented with polydipsia and polyuria,and eight with growth retardation.All patients had lower than-normal serum chloride concentration,metabolic alkalosis,and elevated basal renin activity and aldosterone,and seven had hypokalemia.Through treatment of indomethacin and/or potassium chloride,biochemical indicators could roughly restored normal.Conclusion These findings will enrich the human gene mutation database (HGMD) and provide valuable references to the genetic counseling and diagnosis for Chinese population.
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Objective To observe the effect of low-dose paclitaxel concurrent chemotherapy of advanced non-small cell lung cancer in the application in the treatment, analysis of the nursing intervention. Methods From February 2014 to March 2017 in our hospital 31 cases of advanced non-small cell lung cancer patients as the research object, the patients were given low-dose paclitaxel concurrent radiotherapy chemotherapy in the treatment of patients with adverse reactions, according to the selection of targeted nursing intervention, observation of this group of patients. Results The degree of toxicity is the after treatment of the patients with psychological, clinical, prevention of infection, diet and other aspects of nursing intervention, all patients with adverse reactions were mitigated, and completed the treatment program. Conclusion Low dose paclitaxel concurrent radiotherapy and chemotherapy and the application of nursing intervention in advanced non-small cell lung cancer with precise, can effectively alleviate the adverse reaction in the treatment of patients, as a disease. It provides the guarantee for the prognosis of the disease and has practical value.
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Objective To observe the effect of low-dose paclitaxel concurrent chemotherapy of advanced non-small cell lung cancer in the application in the treatment, analysis of the nursing intervention. Methods From February 2014 to March 2017 in our hospital 31 cases of advanced non-small cell lung cancer patients as the research object, the patients were given low-dose paclitaxel concurrent radiotherapy chemotherapy in the treatment of patients with adverse reactions, according to the selection of targeted nursing intervention, observation of this group of patients. Results The degree of toxicity is the after treatment of the patients with psychological, clinical, prevention of infection, diet and other aspects of nursing intervention, all patients with adverse reactions were mitigated, and completed the treatment program. Conclusion Low dose paclitaxel concurrent radiotherapy and chemotherapy and the application of nursing intervention in advanced non-small cell lung cancer with precise, can effectively alleviate the adverse reaction in the treatment of patients, as a disease. It provides the guarantee for the prognosis of the disease and has practical value.
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OBJECTIVE@#To study the pathological changes of genioglossus with transmission electron microscope (TEM) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) dominated by lingual region obstruction, and to explore the role of tongue organizations in the pathogenesis and its clinical significance.@*METHOD@#Thirty-eight cases of genioglossus were collected from the patients received UPPP and partial glossectomy (3060 severe group 15 cases), 6 adult patients without oropharyneal and hypopharyneal obstructive disease received tongue tumor resection or trauma debridement surgery were collected as control group. The features of morphological changes in genioglossus were observed by TEM.@*RESULT@#Under the TEM, in the control group,the muscle fibers of the genioglossus organization arranges regular, mitochondrial shape between muscle was regular; The below 3 kinds of variations existed simultaneously in all genioglossus specimens of all the OSAHS patients. In the mild group, myofibrillar atrophied, arranged sloppily, the gap was increased, localized filaments were edema, connective tissue between muscle bundles was proliferated, mitochondria were swelling, some were spherical, crests were still clear; In the moderate group, myofibrillar obviously atrophied with different diametric sizes and disorderliness, the Z lines were shortened or distorted, part of the myofibrillar ruptured, dissolved or disappeared, the connective tissues between muscle bundles were obviously proliferated, mitochondria were swellen, vacuolar degeneration, crests were vague, shorten and irregulatio; In the severe group, a large number of myofibrillar were fractured, dissolved, disorganized, integrated condensate lumpy, spotty or flake arranged, Z-lines were distorted or disappeared. Mitochondria were sizes, showed vacuolar degeneration, crests were disappeared, some changes were flocculent, mitochondria accumulation phenomenon was visible in some samples. Moreover, with the AHI increased, the occurence ratio of mild changes was decreased while severe changes occurence ratio increased.@*CONCLUSION@#The changes of genioglossus and mitochondrial in OSAHS patients is a continuous, progressive process, moverover, with the aggravation of OSAHS, genioglossus histopathological changes had gradually worsening tendency.
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Adult , Humans , Glossectomy , Mitochondria , Muscle, Skeletal , Pathology , Sleep Apnea, Obstructive , Tongue , PathologyABSTRACT
@#ObjectiveTo explore the action of the psychointervension for older hypertensives in community.Methods50 older hypertensives were divided into the experimental group and the control group (with 25 cases in each group),the former received psychointervension combined body therapy and the later only received body therapy. A half of a year experiment period was made. Differences between two groups in blood pressure and SCL-90 before and after the experiment were compared and evaluated.ResultsThe mentation of older hypertensives is worse than the normal. There are distinct differences between two groups in the improvement of mentation and the stability of blood pressure (P<0.01). Conclusions It is an active effect to strengthen psychointervension for therapy of older hypertensives in community.