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ABSTRACT Objective: Transbronchial lung cryobiopsy (TBCB) has developed rapidly and has become one of the research hotspots of lung biopsy technology. The present study sought to evaluate the efficacy of TBCB guided by radial-probe EBUS (RP-EBUS) and a guide sheath (GS) without fluoroscopy for peripheral pulmonary lesions. Methods: In this retrospective study, McNemar's test was used in order to compare TBCB and transbronchial forceps biopsy (TBFB) in terms of diagnostic performance. A multivariate logistic regression model was designed to explore the association between predictive variables and the diagnostic yield of TBCB. Results: A total of 168 patients underwent GS-guided RP-EBUS. Of those, 157 had lesions that were visible and 11 had lesions that were not. Of those 157 patients, 24 were excluded because of missing data or an unclear final diagnosis. Therefore, 133 patients underwent RP-EBUS-GS-guided TBFB and TBCB. The pooled diagnostic yield of RP-EBUS-GS-guided TBCB without fluoroscopy was 71.5% (103/144). In 133 patients, the diagnostic yield of TBCB was significantly higher than that of TBFB (77.4% vs. 59.4%; p < 0.05). Multivariate analysis indicated that lesion size and site were independently associated with the diagnostic yield of TBCB (OR = 2.8, p = 0.03 and OR = 4.1, p = 0.01, respectively), although cryoprobe size was not. There was no significant difference between the 1.1-mm cryoprobe and the 1.9-mm cryoprobe in terms of diagnostic performance (78.4% vs. 76.8%; p > 0.05). Conclusions: GS-guided RP-EBUS is regarded as a practical option for guiding cryobiopsy, although it may not be able to replace fluoroscopy. Peripheral pulmonary lesions not located in the upper lobes or larger than 30 mm are significantly associated with a higher diagnostic yield of cryobiopsy.
RESUMO Objetivo: A criobiópsia transbrônquica (CBTB) desenvolveu-se rapidamente e tornou-se um dos focos de pesquisa de tecnologia de biópsia pulmonar. O presente estudo buscou avaliar a eficácia da CBTB guiada por EBUS radial com bainha guia sem fluoroscopia no diagnóstico de lesões pulmonares periféricas. Métodos: Neste estudo retrospectivo, o teste de McNemar foi usado para comparar a CBTB e a biópsia transbrônquica com pinça (BTB) quanto ao desempenho diagnóstico. Um modelo de regressão logística multivariada foi criado para explorar a relação entre variáveis preditivas e o rendimento diagnóstico da CBTB. Resultados: Um total de 168 pacientes foram submetidos a EBUS radial com bainha guia. Destes, 157 apresentavam lesões que puderam ser visualizadas e 11 apresentavam lesões que não puderam ser visualizadas. Dos 157 pacientes, 24 foram excluídos em virtude de dados incompletos ou diagnóstico final incerto. Portanto, 133 pacientes foram submetidos a BTB e CBTB guiadas por EBUS radial com bainha guia. O rendimento diagnóstico combinado da CBTB guiada por EBUS radial com bainha guia foi de 71,5%. O rendimento diagnóstico da CBTB foi significativamente maior que o da BTB (77,4% vs. 59,4%; p < 0,05). A análise multivariada indicou que o tamanho e o local da lesão apresentaram relação independente com o rendimento diagnóstico da CBTB (OR = 2,8, p = 0,03 e OR = 4,1, p = 0,01, respectivamente); o tamanho da criossonda, por sua vez, não apresentou relação com o rendimento diagnóstico da CBTB. Não houve diferença significativa entre a criossonda de 1,1 mm e a de 1,9 mm no que tange ao desempenho diagnóstico (78,4% vs. 76,8%; p > 0,05). Conclusões: EBUS radial com bainha guia é uma opção prática para guiar a criobiópsia, embora talvez não possa substituir a fluoroscopia. Lesões pulmonares periféricas que não estejam nos lobos superiores ou que tenham mais de 30 mm apresentam relação significativa com maior rendimento diagnóstico da criobiópsia.
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Abstract Introduction The relationship between humidity and systemic lupus erythematosus (SLE) has yielded inconsistent results in prior research, while the effects of humidity on lupus in animal experiments and its underlying mechanism remain inadequately explored. Methods The present study aimed to investigate the impact of high humidity (80 ± 5%) on lupus using female and male MRL/lpr mice, with a particular focus on elucidating the role of gut microbiota in this process. To this end, fecal microbiota transplantation (FMT) was employed to transfer the gut microbiota of MRL/lpr mice under high humidity to blank MRL/lpr mice under normal humidity (50 ± 5%), allowing for an assessment of the effect of FMT on lupus. Results The study revealed that high humidity exacerbated lupus indices (serum anti-dsDNA, ANA, IL-6, and IFN- g, and renal pathology) in female MRL/lpr mice but had no significant effect on male MRL/lpr mice. The aggravation of lupus caused by high humidity may be attributed to the increased abundances of the Rikenella, Romboutsia, Turicibacter, and Escherichia-Shigella genera in female MRL/lpr mice. Furthermore, FMT also exacerbated lupus in female MRL/lpr mice but not in male MRL/lpr mice. Conclusion In summary, this study has demonstrated that high humidity exacerbated lupus by modulating gut microbiota in female MRL/lpr mice. The findings underscore the importance of considering environmental factors and gut microbiota in the development and progression of lupus, particularly among female patients.
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Resumo Fundamento A dexmedetomidina (DEX), um agonista específico do receptor α2-adrenérgico, é protetora contra lesão de isquemia/reperfusão miocárdica (I/R). No entanto, a associação entre a cardioproteção induzida pelo pré-condicionamento DEX e a supressão da mitofagia permanece pouco clara. Objetivo Portanto, nosso objetivo foi investigar se o pré-condicionamento com DEX alivia a I/R, suprimindo a mitofagia via ativação do receptor α2-adrenérgico. Método Sessenta corações de ratos isolados foram tratados com ou sem DEX antes de induzir isquemia e reperfusão; um antagonista do receptor α2-adrenérgico, a ioimbina (YOH), também foi administrado antes da isquemia, isoladamente ou com DEX. A frequência cardíaca (FC), pressão diastólica do ventrículo esquerdo (PDVE), pressão diastólica final do ventrículo esquerdo (PDFVE), taxa máxima e mínima de desenvolvimento da pressão ventricular esquerda (±dp/dtmax) e tamanho do infarto do miocárdio foram medidos. A ultraestrutura mitocondrial e as autofagossomas foram avaliadas por microscopia eletrônica de transmissão. O potencial de membrana mitocondrial e os níveis de espécies reativas de oxigênio (ROS) foram medidos usando os ensaios JC-1 e diacetato de diclorodi hidrofluoresceína, respectivamente. Os níveis de expressão das proteínas associadas à mitofagia Beclin1, relação LC3II/I, p62, PINK1 e Parkin foram detectados por western blotting. Resultados Em comparação com o grupo controle, no grupo isquemia/reperfusão, a FC, PDVE e ±dp/dtmax foram notavelmente diminuídas (p<0,05), enquanto os tamanhos da PDFVE e do infarto aumentaram significativamente (p<0,05). O pré-condicionamento com DEX melhorou significativamente a disfunção cardíaca, reduziu o tamanho do infarto do miocárdio, manteve a integridade estrutural mitocondrial, aumentou o potencial de membrana mitocondrial, inibiu a formação de autofagossomas e diminuiu a produção de ROS e a relação Beclin1, relação LC3II/I, expressão PINK1, Parkin e p62(p<0,05). Quando DEX e YOH foram combinados, o YOH cancelou o efeito da DEX, enquanto o uso de YOH sozinha não teve efeito. Conclusão Portanto, o pré-condicionamento DEX foi cardioprotetor contra I/R em ratos, suprimindo a mitofagia por meio da ativação do receptor α2-adrenérgico.
Abstract Background Dexmedetomidine (DEX), a specific α2-adrenergic receptor agonist, is protective against myocardial ischemia/reperfusion injury (MIRI). However, the association between DEX preconditioning-induced cardioprotection and mitophagy suppression remains unclear. Objective Hence, we aimed to investigate whether DEX preconditioning alleviates MIRI by suppressing mitophagy via α2-adrenergic receptor activation. Method Sixty isolated rat hearts were treated with or without DEX before inducing ischemia and reperfusion; an α2-adrenergic receptor antagonist, yohimbine (YOH), was also administered before ischemia, alone or with DEX. The heart rate (HR), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximal and minimal rate of left ventricular pressure development (±dp/dtmax), and myocardial infarction size were measured. The mitochondrial ultrastructure and autophagosomes were assessed using transmission electron microscopy. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were measured using JC-1 and dichloride hydrofluorescein diacetate assays, respectively. The expression levels of the mitophagy-associated proteins Beclin1, LC3II/I ratio, p62, PINK1, and Parkin were detected by western blotting. Results Compared with the control group, in the ischemia/reperfusion group, the HR, LVDP, and ±dp/dtmax were remarkably decreased (p< 0.05), whereas LVEDP and infarct sizes were significantly increased (p< 0.05). DEX preconditioning significantly improved cardiac dysfunction reduced myocardial infarction size, maintained mitochondrial structural integrity, increased mitochondrial membrane potential, inhibited autophagosomes formation, and decreased ROS production and Beclin1, LC3II/I ratio, PINK1, Parkin, and p62 expression(p< 0.05). When DEX and YOH were combined, YOH canceled the effect of DEX, whereas the use of YOH alone had no effect. Conclusion Therefore, DEX preconditioning was cardioprotective against MIRI in rats by suppressing mitophagy via α2-adrenergic receptor activation.
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A UPLC-Q-Orbitrap-MS based metabolomic approach combined with biochemical assay and histopathological inspection were employed to study the intervention effects of Suanzaoren Decoction (SZRD) on chronic unpredictable mild stress (CUMS) depression rats, and to clarify the metabolic regulation pathway of SZRD. The rats were randomly divided into normal control group, CUMS model group, positive drug venlafaxine group, SZRD high (24 g·kg-1) and low (12 g·kg-1) dose groups, respectively. The CUMS model was replicated by subjecting to a variety of stimulus, such as thermal stimulation, ice water swimming, ultrasonic stimulation, tail clamping, day and night reversal, plantar electric shock and so on for rats. After oral administration of drugs for 28 days, the behavioral indexes of rats in each group were observed and the hippocampus and serum samples of rats were collected for biochemical assay and histopathological inspection. Compared with the CUMS model group, low dose and high dose SZRD groups can significantly reduce the immobility time of forced swimming (P < 0.001, P < 0.001), increase the sucrose preference rate (P < 0.01, P < 0.05), the number of crossings (P < 0.05, P < 0.01) and the number of uprights (P < 0.05, P < 0.01) in the open field test, suggesting that SZRD can significantly improve the depression-like behavior of CUMS model rats. In addition, SZRD could significantly reduce the levels of serum IL-6, IL-1β and TNF-α of CUMS model rats. A total of 21 differential metabolites in serum were identified by comparison with the data from the literature and databases. In addition, low-dose SZRD and high-dose SZRD improved the 8 and 11 perturbed potential serum biomarkers that were induced by CUMS, respectively, which related to alanine, aspartic acid and glutamic acid, tryptophan and arachidonic acid metabolism. This study provides a scientific basis for expanding the clinical indications of SZRD. This experiment was approved by the Animal Ethics Committee of Shanxi University (Approval No. SXULL2020028).
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Objective@#To explore the use of personal audio devices and hearing impairment among high school students, so as to provide reference for the development of adolescent hearing health work.@*Methods@#The simple random sampling method was used to collect research data relating to 1 768 high school students. The situation of personal audio players, headphone and hearing damage were investigated by using a self designed questionnaire, so as to identify the related factors of hearing impairment which were analyzed statistically by multivariate Logistic regression.@*Results@#The use rate of PAP and earphones was 98.64% and 94.12 %, respectively, and the use rate of female students(99.68%, 96.42%) was higher than that of male students(97.43%, 91.43 %)( χ 2=16.69, 19.79, P <0.01). Hearing impairment accounted for 13.35%. The Logistic regression analysis showed that PAP service years ( OR =1.59, P <0.05) were related to hearing impairment. Gender ( OR =0.60), in ear earphones ( OR =1.38), earplug earphones ( OR =1.37), and quiet use >1 h ( OR =1.50) were independently influenced with symptoms of hearing impairment during/after earphone use( P <0.05).@*Conclusion@#High usage rates of personal audio equipment among high school students lead to hearing impairment and related symptoms. Non essential use should be reduced.
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@#Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.
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The aim is to study the tissue distribution characteristics of eight effective components in normal rats after oral administration of Ziziphi Spinosae Semen (ZSS) aqueous extract. An ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) analysis method was developed and validated for the determination of four flavonoids and four saponins in rat tissue using puerarin and ginsenoside Re as the internal standard (IS), respectively. Tissue samples including the heart, liver, spleen, lung, kidney, muscle, brain, small intestine, and serum, were collected from each rat at 0.5 h, 1.0 h, and 2.0 h after oral administration of ZSS aqueous extract (15 g·kg-1). All calibration curves exhibited good linearity (r > 0.994 6) over a wide concentration range for all components. The intra-day and inter-day precisions (RSD) at four different levels were both less than 19.77%, and the accuracies (RE) ranged from -19.68% to 19.46%; The extraction recoveries of the eight components ranged from 86.70% to 114.29%, and the matrix effects were from 82.14% to 114.57%. The validated method was successfully applied to the tissue distribution study of the eight components. The levels of swertisin, spinosin, 6‴-feruloylspinosin, and kaempferol-3-O-rutinoside in the small intestine were highest, then followed by the kidney, heart, and liver. Meanwhile, the levels of jujuboside A (JuA), jujuboside B (JuB), and jujuboside A1 (JuA1) in the small intestine were highest, then followed by the lung, spleen, and kidney. The concentrations of betulinic acid in the small intestine were higher than heart, lung, kidney, and liver. The flavonoids and saponins of ZSS with extremely low content could pass through the blood-brain barrier. The research results will provide an experimental basis for explaining the mechanism of nourishing the heart and tranquilizing the mind of ZSS. The animal experimental operations involved in this study followed the regulations of the Animal Ethics Committee of Shanxi University of Chinese Medicine and passed the animal experimental ethical review (No. 2021DW172).
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SUMMARY: The plantaris muscle is located between the soleus and gastrocnemius muscles, within the posterior calf group. Due to degeneration and its loss of plantar-flexion function, the muscle is vestigial in human beings, but it retains clinical significance. Few cases of variation in the plantaris muscle have been reported, and this, therefore, appears to be rare. Nonetheless, absence of this muscle was identified via the dissection of a left lower limb (male), which also indicated the absence of an attachment in the usual position. The present report, which addresses such variation, may provide both inspiration and reference points for the clinical treatment of so-called "tennis leg", and for the use of plantaris muscle for the purposes of clinical, autologous graft repair.
RESUMEN: El músculo plantar se ubica entre los músculos sóleo y gastrocnemio, dentro del grupo posterior de la pierna. Debido a la degeneración y la pérdida de la función de flexión plantar, el músculo es un vestigio en los seres humanos, pero conserva su importancia clínica. Se han informado pocos casos de variación en el músculo plantar y, por lo tanto, esto parece ser raro. No obstante, se observó la ausencia de este músculo durante la disección de un miembro inferior izquierdo (masculino). El presente informe, que aborda dicha variación, puede proporcionar puntos de referencia para el tratamiento clínico de la llamada "pierna de tenista" y para el uso del músculo plantar con fines de reparación clínica con injerto autólogo.
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Humans , Male , Adult , Muscle, Skeletal/anatomy & histology , Anatomic VariationABSTRACT
OBJECTIVE@#To investigate the anti-oxidative effect of ethyl pyruvate (EP) and taurine (TAU) on the quality of red blood cells stored at 4±2 ℃, hemolysis, energy metabolism and lipid peroxidation of the red blood cells in the preservation solution were studied at different intervals.@*METHODS@#At 4±2 ℃, the deleukocyte red blood cells were stored in the citrate-phosphate-dextrosesaline-adenine-1 (CPDA-1) preservation (control group), preservation solution with EP (EP-AS), and TAU (TAU-AS) for long-term preservation. The enzyme-linked immunoassay and automatic blood cell analyzer were used to detect hemolysis and erythrocyte parameters. Adenine nucleoside triphosphate (ATP), glycerol 2,3-diphosphate (2,3-DPG) and malondialdehyde (MDA) kits were used to test the ATP, 2,3-DPG and MDA concentration.@*RESULTS@#During the preservation, the rate of red blood cell hemolysis in EP-AS and TAU-AS groups were significantly lower than that in CPDA-1 group (P<0.01). The MCV of EP-AS group was increased with the preservation time (r=0.71), while the MCV of the TAU-AS group was significantly lower than that in the other two groups (P<0.05). The concentration of ATP and MDA in EP-AS and TAU-AS groups were significantly higher than that in CPDA-1 group at the 14th day (P<0.01). The concentrations of 2,3-DPG in the EP-AS and TAU-AS groups were significantly higher than that in the CPDA-1 group from the 7th day (P<0.01).@*CONCLUSION@#EP and TAU can significantly reduce the red blood cell hemolysis rate, inhibit the lipid peroxidation level of red blood cells, and improve the energy metabolism of red blood cells during storage. The mechanism of EP and TAU may be related to their antioxidation and membrane protection effect, so as to improve the red blood cell quality and extend the preservation time.
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Humans , 2,3-Diphosphoglycerate/metabolism , Adenine , Adenosine Triphosphate/metabolism , Blood Preservation , Citrates/pharmacology , Erythrocytes/metabolism , Glucose/pharmacology , Hemolysis , Pyruvates , Taurine/pharmacologyABSTRACT
Esophageal cancer is a digestive tract malignancy with high morbidity and mortality and mainly occurs in males. The 5-year survival rate is lower than 20%. In China， the morbidity and mortality of esophageal cancer rank the first in the world， seriously threatening national health. The pathogenesis of esophageal cancer is diverse， which is generally considered as the consequence of environmental-genetic-gene interaction. In addition to genetic factors and regional characteristics， gene mutation， RNA interference， DNA damage repair， tumor microenvironment， dietary habit， chronic adverse stimulation， and inflammatory reaction are all involved in the occurrence and development of esophageal cancer. However， there is no unified and accurate conclusion. Clarifying the exact pathogenesis of esophageal cancer is of great significance for its early screening， diagnosis， prevention， treatment， and prognosis. Surgery， radiotherapy， and chemotherapy are the three effective methods for the treatment of esophageal cancer. However， due to the atypical early symptoms， most patients have missed the best operation period when diagnosed， resulting in poor clinical prognosis. Moreover， radiotherapy and chemotherapy will cause side effects such as loss of appetite， low immune function， esophagitis， pneumonia， and malnutrition， which is not conducive to the prognosis and treatment maintenance of patients. With definite efficacies on esophageal cancer， traditional Chinese medicine （TCM）， which is flexible and diverse in the treatment， can primarily or alternatively be involved in the treatment of esophageal cancer. TCM can eliminate postoperative complications and postoperative infections and relieve adverse gastrointestinal reactions， weakened immune function， and organ damage caused by radiotherapy and chemotherapy. It can enhance clinical efficacy and improve the quality of life of patients. Therefore， it is necessary to systematically summarize the clear pathogenesis or risk factors of esophageal cancer and review the clinical characteristics of TCM in the prevention and treatment of esophageal cancer to facilitate the early screening， diagnosis， and treatment of esophageal cancer and promote the application of TCM in the prevention and treatment of esophageal cancer and related adverse reactions.
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Objective To analyze the trends of human schistosomiasis prevalence in Hubei Province from 2004 to 2018, so as to provide the evidence for formulating the schistosomiasis elimination strategy in the province. Methods All data pertaining to human schistosomiasis prevalence in Hubei Province were collected from 2004 to 2018, and the trends for changes in seroprevalence, egg-positive rate and prevalence of human Schistosoma japonicum infection were analyzed using a Joinpoint regression model. Results Both of the numbers of residents seropositive and egg-positive for S. japonicum infections appeared a tendency towards a decline in Hubei Province from 2004 to 2018, and the prevalence of human S. japonicum infections reduced from 6.85% in 2004 to 0 in 2018. Joinpoint regression analysis showed that the prevalence of human S. japonicum infections appeared an overall tendency towards a reduction in Hubei Province from 2004 to 2018 [average annual percent change (AAPC) = −24.1%, P < 0.01], and the trends for the reduction were both significant during the period from 2004 to 2006 [annual percent change (APC) = −35.1%, P < 0.01] and from 2006 to 2018 (APC = −22.1%, P < 0.01). The prevalence of human S. japonicum infections appeared a tendency towards a decline in islet (AAPC = −25.1%, P < 0.01), inner embankment (AAPC = −26.4%, P < 0.01) and hilly subtypes of schistosomiasis-endemic areas (AAPC = −32.5%, P < 0.01) of Hubei Province from 2004 to 2018, and the prevalence all appeared a tendency towards a decline during the infection control stage (from 2004 to 2008), the transmission control stage (from 2009 to 2013) and the transmission interruption stage (from 2014 to 2018) (AAPC = −28.0%, −24.4% and −63.8%, all P values < 0.01). The seroprevalence of human S. japonicum infections appeared an overall tendency towards a decline in Hubei Province from 2004 to 2018 (AAPC = −14.5%, P < 0.01), and the trends for the reduction were both significant during the period from 2004 to 2012 (APC = −8.4%, P < 0.01) and from 2012 to 2018 (APC = −22.1%, P < 0.01). In addition, the egg-positive rate of human S. japonicum infections appeared an overall tendency towards a decline in Hubei Province from 2004 to 2018 (AAPC = −30.6%, P < 0.05), and the trend for the reduction was significant during the period from 2007 to 2014 (APC = −15.5%, P < 0.01). Conclusions The prevalence of human schistosomiasis appeared a tendency towards a decline in Hubei Province from 2004 to 2018, and the islet and inner embankment subtypes of endemic areas are a high priority for schistosomiasis control during the stage moving towards elimination in Hubei Province.
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Suanzaoren Decoction(SZRD) is a classical formula for the clinical treatment of insomnia. This study analyzed the effect of SZRD on endogenous metabolites in insomnia rats based on metabonomics and thereby explored the anti-insomnia mechanism of SZRD. To be specific, DL-4-chlorophenylalanine(PCPA) was used to induce insomnia in rats. Then pathological changes of the liver and brain were observed and biochemical indexes such as 5-hydroxytryptamine(5-HT), dopamine(DA), glutamate(Glu), γ-aminobutyric acid(GABA), and norepinephrine(NE) in the hippocampus and prostaglandin D2(PGD2), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and IL-6 in the serum of rats were detected. On this basis, the effect of SZRD on PCPA-induced insomnia rats was preliminarily assessed. The metabolic profile of rat serum samples was further analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were combined with t-test and variable importance in projection(VIP) to identify differential metabolites, and MetaboAnalyst 5.0 was employed for pathway analysis. The results showed that SZRD could improve the pathological changes of brain and liver tissues, increase the levels of neurotransmitters 5-HT, DA, and GABA in hippocampus and the level of PGD2 in hypothalamic-pituitary-adrenal axis(HPA axis), and reduce the levels of IL-1β and TNF-α in serum of insomnia rats. Metabonomics analysis yielded 12 significantly changed potential metabolites: 5-aminovaleric acid, N-acetylvaline, L-proline, L-glutamate, L-valine, DL-norvaline, D(-)-arginine, pyroglutamic acid, 1-methylguanine, L-isoleucine, 7-ethoxy-4-methylcoumarin, and phthalic acid mono-2-ethylhexyl ester(MEHP), which were related with multiple biochemical processes including metabolism of D-glutamine and D-glutamate, metabolism of alanine, aspartate, and glutamate, metabolism of arginine and proline, arginine biosynthesis, glutathione metabolism. These metabolic changes indicated that SZRD can improve the metabolism in insomnia rats by regulating amino acid metabolism.
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Animals , Rats , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal , Hypothalamo-Hypophyseal System , Metabolomics/methods , Pituitary-Adrenal System , Sleep Initiation and Maintenance Disorders/drug therapy , Tandem Mass SpectrometryABSTRACT
Resumo Fundamento A cardiopatia isquêmica atraiu muito atenção devido às altas taxas de mortalidade, custos do tratamento e a crescente morbidade na população jovem. Estratégias de reperfusão reduziram a mortalidade. Porém, a reperfusão pode levar à morte do cardiomiócito e subsequente dano irreversível ao miocárdio. No momento, não há um tratamento eficiente e direcionado para a lesão de isquemia-reperfusão (I/R). Objetivos Avaliar se a dexmedetomidina (DEX) tem efeito protetivo na I/R do miocárdio e explorar os possíveis mecanismos por trás dela. Métodos Corações de ratos foram perfundidos com o sistema de perfusão de Langendorff e aleatoriamente distribuídos em cinco grupos: grupo controle, perfundido com solução de Krebs-Henseleit (K-H) por 205 minutos sem isquemia; e quatro grupos de teste que foram submetidos a 40 minutos de isquemia global e 120 minutos de reperfusão. O Grupo DEX, o grupo ioimbina (IO) e o grupo DEX + IO foram perfundidos com DEX (10 nM), IO (1 μM) ou a combinação de DEX e IO antes da reperfusão, respectivamente. A hemodinâmica cardíaca, o tamanho do infarto do miocárdio e a histologia do miocárdio foram avaliados. A expressão da proteína-78 regulada pela glicose (GRP78), a proteína quinase do retículo endoplasmático (PERK), a PERK fosforilada, o fator de iniciação eucariótico 2α (eIF2α), eIF2α fosforilado, o fator de transcrição 4 (TCF-4) e a proteína homóloga à proteína ligadora do acentuador CCAAT (CHOP) foram avaliados. P< 0,05 foi considerado para indicar a diferença estatisticamente significativa. Resultados O pré-condicionamento com DEX melhorou a função cardíaca nos corações com I/R, reduziu o infarto do miocárdio, a apoptose do miocárdio e a expressão de GRP78, p-PERK, eIF2α, p-eIF2α, TCF-4 e CHOP. Conclusões O pré-tratamento com DEX reduziu a lesão de I/R no miocárdio ao suprimir a apoptose, o que foi induzido pela via PERK.
Abstract Background Ischemic heart disease has attracted much attention due to its high mortality rates, treatment costs and the increasing morbidity in the young population. Strategies for reperfusion have reduced mortality. However, reperfusion can lead to cardiomyocyte death and subsequent irreversible myocardial damage. At present, the timely and targeted treatment of ischemia-reperfusion (I/R) injury is often lacking. Objectives To evaluate if dexmedetomidine (DEX) has a protective effect in myocardiual I/R and explore the possible mechanism behind it. Methods Rat hearts were perfused with a Langendorff perfusion system, and randomly assigned to five groups: control group, perfused with Krebs-Henseleit (K-H) solution for 205 minutes without ischemia; and four test groups that underwent 40 minutes of global ischemia and 120 min of reperfusion. The DEX group, the yohimbine (YOH) group and the DEX + YOH group were perfused with DEX (10 nM), YOH (1 μM) or the combination of DEX and YOH prior to reperfusion, respectively. Cardiac hemodynamics, myocardial infarct size, and myocardial histology were evaluated. The expression of glucose-related protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phosphorylated PERK, eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α, activating transcription factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) were assessed. P<0.05 was considered to indicate a statistically significant difference. Results DEX preconditioning improved the cardiac function of I/R hearts, reduced myocardial infarction, myocardial apoptosis, and the expression of GRP78, p-PERK, eIF2α, p-eIF2α, ATF4 and CHOP. Conclusions DEX pretreatment reduced myocardial I/R injury by suppressing apoptosis, which was induced by the PERK pathway.
Subject(s)
Animals , Rats , Myocardial Reperfusion Injury/prevention & control , Reperfusion Injury , Myocardial Ischemia , Dexmedetomidine/pharmacology , Myocardial Infarction/prevention & control , Myocardial Infarction/drug therapy , Signal TransductionABSTRACT
Medicinal plant germplasm resources are the foundation of the modern development of traditional Chinese medicine. In-depth study of medicinal plant germplasm resources is a prerequisite for cultivating fine varieties and ensuring the output and standard quality of traditional Chinese medicine（TCM）. Traditional identification methods start with appearance and are greatly affected by natural environment and human factors，with a low efficiency and accuracy of identification are generally low molecularin general. Due to such advantages as easy operation，high sensitivity，accurate results， molecular biology technology has been widely used in the related research of relevant studies for medicinal plant germplasm resources due to its advantages of easy operation，high sensitivity，accurate results，etc. It mainly involving the distinction between wild and cultivated products，researchstudy on substitutes of TCM，identification of Chinese patent medicine，good variety marker breeding，genetic diversity researchstudy，genetic map establishment and omics research，etcstudy. Among them，omics researchstudy is divided into genomics，transcriptomics，metabolomics，and proteomics due toby different analysis purposes. Genomics is divided into three sub-fields namely structural genomics，functional genomics， and comparative genomics. Eukaryotes Because eukaryotes have nuclei and organelles，so omics researchstudy also includes chloroplast genomics，mitochondrial genomics，nuclear genomics，and plastid genomics. Among them，the chloroplast genome has a simple structure，small molecular weight，and good conservation，while the mitochondrial genome has a strong variability and complex structure，the nuclear genome data isfeatures complex， data and the nucleus contains no ribosomes in nucleus，resulting in spatiotemporal differences in the translation process，even if repeated repeatedly test， the result of and the test is alsoresults remained uncertain， even after repeated tests. The molecular biology technology and omics researchstudy involved in theby current medicinal plant researchstudy still hashave shortcomings，and there iswith a large room for development，which needs and need further improvement and supplementation. This articlepaper successively introduces the characteristics and applications of cytology，molecular markers，and omics researchstudy techniques in the identification of medicinal germplasm resources，providingin order to provide a reference for subsequent identification，development and utilization of medicinal plant germplasm resources.
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Objective:A comprehensive and in-depth analysis method for identification of chemical constituents in Suanzaoren Tang granules was established. Method:Ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS/MS） was employed with the mobile phase of 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-8 min， 5%-17%B； 8-10 min， 17%B； 10-11 min， 17%-18%B； 11-12 min， 18%-20%B； 12-17 min， 20%-23%B； 17-22 min， 23%-33%B； 22-30 min， 33%-60%B； 30-32 min， 60%-100%B； 32-36 min， 100%B）， the flow rate of 0.3 mL·min<sup>-1</sup> and electrospray ionization （ESI）. High quality MS/MS data were scanned in positive and negative ion modes with scanning range of <italic>m</italic>/<italic>z</italic> 50-1 500. The local database of the chemical components from different Chinese medicines in Suanzaoren Tang granules was established by SCIEX OS software. Then the chemical components in Suanzaoren Tang granules were characterized by matching with the local database and comparing with the reference substance and literature information. Result:A total of 134 compounds were characterized and identified under positive and negative ion modes， mainly including flavonoids， triterpenoids， phthalides， steroidal saponins， alkaloids and organic phenolic acids. In addition， the sources of Chinese medicines for all compounds identified in Suanzaoren Tang granules were assigned. Among them， 41 were from Ziziphi Spinosae Semen， 11 were from Poria， 22 were from Anemarrhenae Rhizoma， 28 were from Chuanxiong Rhizoma and 35 were from Glycyrrhizae Radix et Rhizoma. Conclusion:The method can be used to identify the chemical constituents in Suanzaoren Tang granules systematically， quickly and accurately， which can provide a new strategy for the rapid and accurate identification of other Chinese patent medicines.
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Objective:To develop the specific molecular markers of <italic>Codonopsis</italic> plants and better identify their germplasm resources considering the significant difference in active ingredients of Codonopsis Radix from various origins and producing areas. Method:Such bioinformatics software as Primer 5.0， NTSYS-pc 2.10e， and PopGene 32 were used for searching the simple sequence repeat （SSR） markers of <italic>C. minima </italic>chloroplast genome， <italic>C. tsinlingensis</italic> chloroplast， and <italic>C. lanceolata </italic>mitochondrial sequences， and 120 pairs of SSR primers were designed by Primer 5.0. Then 16 pairs of cpSSR primers and 10 pairs of mtSSR primers with good screening effect and high polymorphism were selected for analyzing the interspecific versatility of 20 samples. Result:The results showed that 66 cpSSR primer sites and 26 mtSSR sites were identified from the genome sequences， with 86.20% of single nucleotide， 6.9% of dinucleotide， and 6.9% of trinucleotide for <italic>C. minima </italic>chloroplast， 83.78% of single nucleotide，13.51% of dinucleotide， and 2.71% of trinucleotide for <italic>C. tsinlingensis</italic> chloroplast， and 46.15% of single nucleotide and 53.85% of dinucleotide for <italic>C. lanceolata </italic>mitochondria. As demonstrated by polymerase chain reaction （PCR） identification results， the developed 26 pairs of SSR primers had good applicability in the genus<italic> Codonopsis</italic>. The analysis by NTSYS-pc 2.10e revealed that the genetic similarity coefficients of 20 samples were within the range of 0.38-1.00， and they were divided into two subgroups at a threshold of 0.69. Four pairs of polymorphic primers were screened out in the diversity analysis of 20 samples using PopGene 32. The number of observed alleles （<italic>Na</italic>） was 12， and the effective number of alleles （<italic>Ne</italic>） ranged from 1.362 9 to 2.605 9. The percentage of polymorphic loci （PPL） at each site was 100%， and the average values of genetic parameters<italic> Ho</italic>， <italic>He</italic>， and <italic>I</italic> at each site were 0.555 8， 0.444 2， and 0.753 2， respectively， indicating high polymorphism at each site. The screened four pairs of primers were utilized for DNA fingerprinting of the 20 samples， and it was found that the DNA fingerprints enabled the identification of these 20 samples. Conclusion:This study has provided a molecular basis for the study of the genetic relationship between plants in species <italic>Codonopsis</italic> and the intraspecific genetic differentiation.
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Objective To establish an indicator system for assessment of schistosomiasis transmission risk after transmission interruption in Hubei Province, so as to provide insights into the precise control of schistosomiasis. Methods The indicator system was preliminarily established based on data collection, literature review, expert interviews. Two rounds of expert consultation were performed. The indicator system was screened based on the importance, operability, sensitivity and comprehensive score of the indicators, and the weights of each indicator were calculated. The credibility of the Delphi method was evaluated by calculating the active coefficient of the experts, degree of expert authority and coordination levels of experts’ opinions. Results An indicator system for assessment of schistosomiasis transmission risk was preliminarily established, including 3 primary indicators, 12 secondary indicators and 44 tertiary indicators. A Delphi consultation was performed among 17 experts participating in schistosomiasis control, management and research. Following two rounds of consultation, a risk assessment indicator system was finally constructed, including 3 primary indicators, 10 secondary indicators and 35 tertiary indicators. Among the primary indicators, the variable with the highest normalized weight was the current status of schistosomiasis (0.420 2), followed by social factors (0.397 3) and natural environments (0.182 5). Among the secondary indicators, those with high combined weights included risk monitoring (0.142 3), current snail status (0.140 1), and current prevalence of human and livestock infections (0.137 8). Among the tertiary indicators, those with high combined weights included the positive rate of wild feces (0.049 8), the prevalence of snail infections (0.047 4), and the area of snail habitats submerged by floods (0.046 8). During the two-round consultation, the active coefficients of the experts were 85.00% and 100.00%, the degree of expert authority was both 0.75 and greater, and the coordination levels of experts’ opinions were 0.405 to 0.521 and 0.592 to 0.695 (all P values < 0.05). Conclusion An indicator system for assessment of schistosomiasis transmission risk is successfully established after transmission interruption in Hubei Province based on the Delphi method, which provides insights into the identification of the schistosomiasis transmission risk and the targets for schistosomiasis control in Hubei Province.
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OBJECTIVE@#To investigate the expression and clinical significance of serum protein ROCK2 in patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The patients were divided into cGVHD group and control group (without cGVHD). The expression levels of serum protein ROCK2 were detected by ELISA in patients with or without cGVHD after allo-HSCT.@*RESULTS@#The expression level of ROCK2 in serum of cGVHD patients was significantly higher than those in control group, moreover, the expression level of ROCK2 in severe cGVHD group was significant higher than that in moderate and mild cGVHD group (P<0.001). The expression level of ROCK2 was significantly decreased in the serum of cGVHD patients after treatment（P＜0.01）; the expression level of ROCK2 was significantly higher in the serum of cGVHD patients with lung as the target organ（P＜0.01）. The median survival time of patients with severe cGVHD were significantly shorter than that of patients with mild and moderate cGVHD（P＜0.05）.@*CONCLUSION@#ROCK2 shows certain reference value in the evaluation of severity and prognosis of cGVHD, and may be a new target for the treatment of cGVHD.
Subject(s)
Humans , Blood Proteins , Chronic Disease , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , rho-Associated KinasesABSTRACT
@#Small for gestational age ( SGA ),one of the major adverse pregnancy outcomes, significantly increases the risk of perinatal death and metabolic diseases in adulthood. It is of great significance to strengthen early surveillance and intervention for SGA prevention. Dyslipidemia during pregnancy, as a common metabolic disorder, has been considered to correlate with the increased risk of SGA; however, the epidemiological evidence is still controversial. We have systematically reviewed the recent studies related to the association between serum lipid level during pregnancy and the risk of SGA, so as to provide reference for prevention and intervention of SGA.
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Stroke is the second most common cause of death after cancer worldwide and a major cause of acquired disability in adults. Overwhelming majority of strokes are caused by cerebral ischemia and are classified as ischemic stroke. Microglia are the resident immune cells and play dual roles in response to ischemia injury in the central nervous system (CNS). On the one hand, microglia may contribute to tissue function recovery process by promoting inflammation resolution, cellular debris clearance, nerve regeneration and synapse remodeling. On the other hand, excessive activation of microglia aggravates nerve damage after ischemic injury. Here, we briefly describe the mechanism of microglia activation after stroke, and comprehensively review the dual role of microglia in neurodegeneration and regeneration after stroke. In-depth exploration of the cytotoxic and protective mechanisms of microglia will provide new targets and new strategies for stroke treatment.