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Objective@#Individuals with dementia are at a substantially elevated risk for mortality; however, few studies have examined multimorbidity patterns and determined the inter-relationship between these comorbidities in predicting mortality risk. @*Methods@#This is a prospective cohort study. Data from 6,556 patients who were diagnosed with dementia between 1997 and 2012 using the Taiwan National Health Insurance Research Database were analyzed. Latent class analysis was performed using 16 common chronic conditions to identify mortality risk among potentially different latent classes. Logistic regression was performed to determine the adjusted association of the determined latent classes with the 5-year mortality rate. @*Results@#With adjustment for age, a three-class model was identified, with 42.7% of participants classified as “low comorbidity class (cluster 1)”, 44.2% as “cardiometabolic multimorbidity class (cluster 2)”, and 13.1% as “FRINGED class (cluster 3, characterized by FRacture, Infection, NasoGastric feeding, and bleEDing over upper gastrointestinal tract).” The incidence of 5-year mortality was 17.6% in cluster 1, 26.7% in cluster 2, and 59.6% in cluster 3. Compared with cluster 1, the odds ratio for mortality was 9.828 (95% confidence interval [CI]=6.708–14.401; p<0.001) in cluster 2 and 1.582 (95% CI=1.281–1.953; p<0.001) in cluster 3. @*Conclusion@#Among patients with dementia, the risk for 5-year mortality was highest in the subpopulation characterized by fracture, urinary and pulmonary infection, upper gastrointestinal bleeding, and nasogastric intubation, rather than cancer or cardiometabolic comorbidities. These findings may improve decision-making and advance care planning for patients with dementia.
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Tigliane type macrocyclic diterpenoids with special structures and diverse bioactivities are mainly extracted from plants of Euphorbiaceae and Thymelaeaceae. According to the different functional groups, they can be classified into types of phorbol esters, C-4 deoxyphorbol esters, C-12 deoxyphorbol esters, C-16 or C-17 substituted phorbol esters and others. Most of them present promising antiviral activities and cytotoxic activities and are expected to be developed as candidates for anti-AIDS, anti-tuberculosis, and anti-tumor clinical trials, demonstrating great potential for the application in healthcare. This paper reviews 115 novel tigliane-type diterpenoids discovered since 2013 and summarize their chemical structures and bioactivities, aiming to lay a foundation for further development and utilization of these compounds and provide new ideas for the development of clinical drugs.
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Forbóis , Estrutura Molecular , Diterpenos/química , Antivirais , Ésteres de ForbolRESUMO
AIM: To explore Bland-Altman analysis of corneal curvature and astigmatism measured by new swept-source optical coherence tomography(SS-OCT)and Scheimpflug anterior segment analyzer in patients with age-related cataract.METHODS: A total of 177 patients(282 eyes)with age-related cataract admitted to the hospital between January and December 2021 were enrolled. The steep-axis curvature(Ks), flat-axis curvature(Kf), mean corneal curvature(Km), corneal astigmatism and astigmatism axis of anterior corneal surface, posterior surface and the whole cornea were measured by SS-OCT and Scheimpflug anterior segment analyzer respectively. All parameters were detected by paired sample t-test, intra-group repeatability test, Pearson correlation and Bland-Altman consistency analysis.RESULTS: There was no significant difference in Ks, Kf and Km of anterior corneal surface measured by SS-OCT and Scheimpflug anterior segment analyzer(P&#x003E;0.05). Ks, Kf and Km of posterior corneal surface and whole cornea measured by Scheimpflug anterior segment analyzer were all greater than those measured by SS-OCT(P&#x003C;0.05). There was no significant difference in astigmatism and axial values of anterior corneal surface, posterior surface and whole cornea measured by SS-OCT and Scheimpflug anterior segment analyzer(P&#x003E;0.05). The intraclass correlation coefficient(ICC)of all parameters was greater than 0.88, indicating a good intra-group repeatability. Ks, Kf, Km, astigmatism and axis of anterior corneal surface, posterior surface and whole cornea measured by SS-OCT were positively correlated with those measured by Scheimpflug anterior segment analyzer(P&#x003C;0.05). Bland-Altman consistency analysis showed that Ks, Kf, Km, corneal astigmatism and axis of anterior corneal surface, posterior surface and whole cornea measured by SS-OCT were highly consistent with those measured by Scheimpflug anterior segment analyzer(P&#x003C;0.05).CONCLUSION: The corneal curvature and astigmatism parameters measured by new SS-OCT are highly consistent with those measured by Scheimpflug anterior segment analyzer, which can be applied in the diagnosis of corneal curvature and astigmatism in patients with age-related cataract.
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ObjectivesBased on the changes of lung lesions in patients with COVID-19 at different stages, a nomogram model describing CT image features was established by radiomics method to explore its efficacy in predicting the progression of the disease. MethodsThis retrospective study enrolled 136 patients with COVID-19 pneumonia who received at least two CTs including three cohorts (training cohort and validation cohort 1 and 2). Patients in the training cohort were divided into three groups according to time between onset of fever symptoms and the first CT. The clinical manifestations and CT features of each group were analyzed and compared. A nomogram to predict disease progression was constructed according to the CT features of the patients, and its performance was evaluated. ResultsThe training cohort consisted of 41 patients.A nomogram was generated to predict disease progression based on three CT features: irregular strip shadow, air bronchial sign, and the proportion of lesions with irregular shape ≥50%. AUC(95%CI)=0.906(0.817,0.995).The C index of the training cohort was 0.906, and the C index of the internal verification was 0.892. AUC(95%CI)of the validation cohort 1 (34 cases) =0.889(0.793,0.984);AUC(95%CI)of the validation cohort 2 (61 cases)=0.876(0.706,1.000).The calibration curves show that the predicted values of the nomogram are in good agreement with the observed values. ConclusionThe nomogram model based on CT radiomics can predict the outcome of lung lesions in patients with high sensitivity and specificity.According to the changes of CT image characteristics of patients with COVID-19, lung lesions will be improved when the proportion of irregular cable shadow, air bronchogram and irregular lesions is greater than 50%.
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Cinnamomum camphora is an important economic tree species in China. According to the type and content of main components in the volatile oil of leaf, C. camphora were divided into five chemotypes, including borneol-type, camphor-type, linalool-type, cineole-type, and nerolidol-type. Terpene synthase(TPS) is the key enzyme for the formation of these compounds. Although several key enzyme genes have been identified, the biosynthetic pathway of(+)-borneol, which has the most economic value, has not been reported. In this study, nine terpenoid synthase genes CcTPS1-CcTPS9 were cloned through transcriptome analysis of four chemical-type leaves. After the recombinant protein was induced by Escherichia coli, geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) were used as substrates for enzymatic reaction, respectively. Both CcTPS1 and CcTPS9 could catalyze GPP to produce bornyl pyrophosphate, which could be hydrolyzed by phosphohydrolase to obtain(+)-borneol, and the product of(+)-borneol accounted for 0.4% and 89.3%, respectively. Both CcTPS3 and CcTPS6 could catalyze GPP to generate a single product linalool, and CcTPS6 could also react with FPP to generate nerolidol. CcTPS8 reacted with GPP to produce 1,8-cineol(30.71%). Nine terpene synthases produced 9 monoterpene and 6 sesquiterpenes. The study has identified the key enzyme genes responsible for borneol biosynthesis in C. camphora for the first time, laying a foundation for further elucidating the molecular mechanism of chemical type formation and cultivating new varieties of borneol with high yield by using bioengineering technology.
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Cinnamomum camphora/enzimologia , Alquil e Aril Transferases/químicaRESUMO
Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
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Feminino , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Prognóstico , Linfoma de Células B , Imuno-Histoquímica , Cadeias Pesadas de Imunoglobulinas/uso terapêuticoRESUMO
Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T. wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T. wilfordii.
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AIM: To investigate the efficacy of the first follow-up visit after daily partial or full-day occlusion of the dominant eye in patients with unilateral amblyopia and assess the maximum efficacy produced by different amounts of occlusion.METHODS: A retrospective clinical study was conducted on 135 cases of unilateral amblyopia cured in our hospital's outpatient clinic from January 2020 to December 2021. They were divided into 2h/d occlusion group, 6h/d occlusion group and all-day occlusion group according to the duration of occlusion, with fine sight training of amblyopic eyes. The effect of the first dose(baseline visual acuity-first review visual acuity), cured visual acuity, stereo vision at the first review and cure time of amblyopic eyes were recorded. The factors affecting the first dose effect in patients with unilateral amblyopia were also analyzed.RESULTS: All patients had a baseline visual acuity of 0.4(0.22, 0.52), a first follow-up visual acuity of 0.22(0.15, 0.3), a first-dose effect of 0.1(0.08, 0.18), and a visual acuity of 0(-0.08, 0.05)when amblyopia cured. The first-dose effects were 0.08(0.07, 0.12)for patients in the 2h/d occlusion group, 0.18(0.08, 0.3)for the 6h/d occlusion group, and 0.10(0.08, 0.18)for the all-day occlusion group. The most significant first-dose effect was the 6h/d occlusion group(P<0.05); Analysis of different influencing factors showed that the highest values of the first-dose effect of 6h/d occlusion were in the 3-6 years group, 7-12 years group, female group, strabismic amblyopia group and mild to moderate group(P<0.05); Furthermore, the first dose effect of the 6h/d occlusion was positively correlated with cure time of amblyopic eyes(rs=0.334, P=0.038). At the first follow-up, 21 cases(53.8%)had improved Titmus stereo visual acuity in the 6h/d occlusion group, which was higher than that in the 2h/d and all-day occlusion groups [16 cases(41.0%), 13 cases(22.8%), P<0.017].CONCLUSIONS: For monocular amblyopia, the first-dose effect of 6h/d occlusion treatment was the most significant, and the recovery of stereopsis was the best.
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OBJECTIVE@#To evaluate the prognostic value of GELTAMO-IPI for patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#The clinical data of 238 newly diagnosed DLBCL patients treated in Shanxi Cancer Hospital from September 2011 to March 2016 were collected retrospectively, the risk stratification and prognostic evaluation of the patients were analyzed according to GELTAMO-IPI. Progression-free survival (PFS) and overall survival (OS) of the patients were analyzed by the Kaplan-Meier method, COX regression analysis was used to compare the risk of death and progress in each risk group. Harrell's C statistics was used to compare the prognostic stratification ability of each model.@*RESULTS@#The 3-year OS rate statistics showed that both IPI and GELTAMO-IPI could distinguish low risk group and Low-intermediate risk group, but the prognosis stratification ability of IPI was better (IPI: HR=5.085, P0.05). GELTAMO-IPI could distinguish High-intermediate risk group from high risk group (GELTAMO-IPI: HR=2.966, P50%). The results of Harrell's C statistics showed the C-index of IPI and GELTAMO-IPI was 0.687 and 0.721 (P<0.001); the C-index of the predicted PFS was 0.672 and 0.700 (P<0.001). It was suggested that the prognostic stratification ability of GELTAM0-IPI be superior to that of IPI, R-IPI, NCCN-IPI.@*CONCLUSION@#GELTAMO-IPI can make a clear distinction between DLBCL patients with different prognosis, especially for high-risk patients, and the prognostic stratification ability of GELTAMO-IPI is significantly better than that of IPI.
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Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
To evaluate the therapeutic effect of Potentilla discolor on 2,4,6-trinitrobenzensulfonic acid(TNBS)-induced experimental ulcerative colitis(UC) in rats and to determine its therapeutic mechanism through mitochondrial autophagy, immune cells, and cytokines. A rat model of UC was established by TNBS-ethanol enema. Rats were divided into six groups: control, UC model, sulfasalazine(positive drug), and high-dose, moderate-dose, and low-dose ethanol extract groups. After 14-day continuous administration of the corresponding drugs, the disease activity index(DAI) and hematoxylin and eosin(HE) were evaluated. The morphological structure of mitochondria was observed by using transmission electron microscope(TEM), mitophagy-related mRNA expression was detected by using Real-time quantitative polymerase chain reaction(qRT-PCR), immune cell differentiation in rat serum was detected by using flow cytometry(FCM), and cytokine expression in colon tissues of rats was detected by protein microarray. The results showed that compared with the model group, each dose group of P. discolor could significantly reduce the DAI of UC model rats, and decrease the degree of inflammatory cells infiltration in the colon tissue of UC model rats. Meanwhile the expressions of T cells and Th cells in the serum increased significantly, the expression of Tc cells in the serum decreased significantly. Transmission electron microscope found that there was fusion of mitochondria and lysosomes in the colon tissue of the administration group. The expressions of mitochondrial autophagy related genes NF-κB, p62 and parkin were significantly increased in colon tissues. The results of protein chip showed that compared with the model group, the high dose group of P. discolor could significantly regulate the expression of cytokines. In conclusion, these results suggested that P. discolor improved TNBS-induced acute ulcerative colitis in rats by regulating the mitochondrial autophagy and the inflammatory factor expression.
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Animais , Ratos , Autofagia , Colite Ulcerativa/genética , Colo , Mitocôndrias , Potentilla/genéticaRESUMO
OBJECTIVE: To investigate the effects of long-term and low dose ionizing radiation on ocular lens opacities of residents living in areas with high natural radiation background(HNRB) in Yangjiang City, China. METHODS: A total of 483 Han residents from Yangjiang City(HNRB area) and 517 from Enping City(control area) were selected as study subjects using a cluster random sampling method. Questionnaire survey and lens examination were carried out. The risk factors of lens opacity and its severity were analyzed by logistic regression analysis. RESULTS: The prevalence rates of lens opacity, cortical opacity and posterior subcapsular opacity in HNRB area were higher than those in control area(60.7% vs 51.6%, 53.4% vs 46.8%, 21.9% vs 9.3%, all P<0.05). There was no significant difference in karyotype turbidity between HNRB area and control area(52.4% vs 47.6%, P>0.05). After adjusting for confounding factors including age, gender, cardiovascular/metabolic diseases, smoking, alcohol drinking and tea drinking, the unconditional logistic regression analysis results showed that the risk of ocular opacity, cortical opacity and posterior subcapsular opacity in residents of HNRB area was higher than that in control area(all P<0.05). Multivariate disordered logistic regression analysis results showed that residents in the HNRB area had a higher risk of grade two karyotype turbidity than grade one karyotype turbidity(P<0.01). Ordered logistic regression analysis results showed that residents in HNRB area had an increased risk of developing severe cortical turbidity(P<0.01). CONCLUSION: Long-term and low dose ionizing radiation exposure may increase the risk of ocular lens opacity, especially cortical and posterior subcapsular cataract, and affect the severity of the disease.
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Chinese traditional medicine compound is the main form of Chinese medicine clinical application. The elucidation of the effective components of traditional Chinese medicine is one of the key scientific issues to promote the modernization of traditional Chinese medicine. At present, there are many research ideas on the effective components of traditional Chinese medicine compounds. By analyzing the current status and existing problems of existing research ideas, the author proposes a "double reduction network pharmacology"(2 R network pharmacology) research method based on "prediction of dominant components-potential target selection". Chemical components with good properties were selected by ADMET property prediction technology, and compared with the blood components and target organ components to determine the dominant components with potential therapeutic effect, that is "reducing constituents"; the potential core regulatory pathway of traditional Chinese medicine compound was enriched by RNA-Seq technology combined with network database, and then the target of traditional Chinese medicine compound was mined based on the signal pathway, that is "reducing targets". To improve the efficiency and accuracy of effective component screening, the network relationship of "component target" was established by the related technology of network pharmacology. The purpose of this study is to provide practical research ideas and methods for clarifying the effective components of traditional Chinese medicine, revealing the law of compatibility of traditional Chinese medicine and clarifying the target of drug action.
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Bases de Dados Factuais , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Projetos de PesquisaRESUMO
BACKGROUND: Opioids can regulate the changes of membrane potential and Ca2+ current in cardiomyocytes, but whether diacetylmorphine can induce the changes of cardiac rhythm, cell action potential and Ca2+ current has not been reported. OBJECTIVE: To explore the effect of diacetylmorphine on action potential and calcium current of isolated cardiomyocytes from neonatal Sprague-Dawley rats. METHODS: Five concentrations of diacetylmorphine (0, 10-2, 10-3, 10-4, 10-5 mol/L) and 20 mol/L verapamil were used to treat the cardiomyocytes of neonatal Sprague-Dawley rats cultured in vitro. The cells were divided into control group, diacetylmorphine group, diacetylmorphine+verapamil group. The latter two groups were treated with diacetylmorphine and diacetylmorphine+verapamil (20 μmol/L), respectively, while the control group was treated with the same amount of PBS. The study protocol was approved by the Animal Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University on May 21, 2018 with approval No. IACUC201805-K1. RESULTS AND CONCLUSION: At 24 hours of culture with different concentrations of diacetylmorphine, the number of cardiomyocytes with abnormal morphology increased significantly in a dose-dependent manner. When the concentration of diacetylmorphine increased, the number of survived cells decreased, with a reduction in the size of cytoplasm and number of pseudopods, the cell membrane was shrunk and the nuclear structure was blurred. Compared with the control group, when diacetylmorphine was added to intervene with the cardiomyocytes, there was a significant difference in the spontaneous beating frequency and rhythm of cardiomyocytes. The negative value of resting membrane potential decreased, while the time course of action potential increased significantly, and the amplitude of action potential decreased significantly. Compared with the control group, the number of cells with changes in the membrane potential significantly increased in the diacetylmorphine group. The addition of verapamil reduced the number of cells with changes in the membrane potential. Compared with the control group, the number of cells with variation of membrane potential was increased to some extents. These findings suggest that diacetylmorphine can induce cardiomyocyte morphological abnormality, increase the spontaneous beating frequency and rhythm of cardiomyocytes, and change the membrane potential and action potential of cardiomyocytes. Verapamil acts as a calcium channel blocker that can improve the rhythm abnormality of cardiomyocytes induced by diacetylmorphine.
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<b>Objective::To investigate the effect of Aconiti Lateralis Praeparata Radix combined with Glycyrrhizae Radix et Rhizoma on mRNA expression of cytochrome P450 (CYP450) enzymes in rat' s heart. <b>Method::Male Sprague Dawley rats were randomly divided into the control group, the inducer group (0.08 g·kg<sup>-1</sup>·d<sup>-1</sup>), the aconite group (0.5 g·kg<sup>-1</sup>·d<sup>-1</sup>), the licorice group (0.5 g·kg<sup>-1</sup>·d<sup>-1</sup>) and the compatibility group (aconite and licorice group 0.5 g·kg<sup>-1</sup>·d<sup>-1</sup>), with 6 rats in each group. In each group, the serum concentrations of aspartate transaminase (AST), creatine kinase (CK) andlactate dehydrogenase (LDH) were respectively measured. Hematoxylin-eosin(HE) staining was used to detect the pathologic changes in the heart tissue of the rats. The expression of several CYP genes were measured. <b>Result::After combination, the contents of AST, CK and LDH were lower than those of the aconite group. At the same time, the pathological results showed cardiac injury in rats in the aconite group, and licorice could alleviate the cardiac injury caused by aconite. At the level of gene transcription, the glycyrrhizae group could up-regulate the expressions of CYP2C11 and CYP2J3 to different degrees (<italic>P</italic><0.05), and the combination of licorice and aconite could up-regulate the expression of CYP2B1, CYP2C11 and CYP2J3 family (<italic>P</italic><0.05). It suggested that the combination could promote the formation of EETs in arachidonic acid(AA) metabolism, and the aconite could up-regulate the expressions of CYP4A1, CYP4A3, CYP4F5 and CYP4F6 in CYP4 family (<italic>P</italic><0.05), promote the formation of 20-hydroxyeicosatetraenoic acid(20-HETE). The combination of aconite and licorice can weaken the ability of aconite, down-regulate the expression of CYP4A3, CYP4F1, CYP4F5 and CYP4F6 family mRNA (<italic>P</italic><0.05), inhibit the formation of 20-HETE and reduce the cardiotoxicity caused by aconite. <b>Conclusion::The combination of licorice and aconite can regulate the expression of CYP450 enzyme in the heart, increase the production of EETs and the content of 20-HETE, and finally play a role in reducing toxicity.
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OBJECTIVE@#To investigate the clinical outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) after surgeries in Yunnan Province.@*METHODS@#We retrospectively analyzed the demographic features, vascular risk factors, severity at admission, and aneurysm locations in 85 patients with aSAH receiving surgical interventions in Yunnan Province. All the patients were treated by aneurysm clipping or coiling and followed up for clinical outcomes and recovery of daily activities evaluated by modified Rankin Scale (mRS) and Activities of Daily Living (ADL) scale, respectively.@*RESULTS@#Thirty-four of the patients (40.0%) underwent aneurysm clipping and 51 (60.0%) underwent aneurysm coiling. During a median follow- up period of 66.23 months (IOR, 12.03 months), 84.7% of the patients had low mRS scores, and 78.8% lived independently. The WFNS grade at admission was significantly correlated with the follow-up mRS scores (95%: 1.48-19.09, =0.011) and ADL (95%: 2.55-28.77, 0.05), but the cost of hospitalization was significantly higher in coiling group than in the clipping group ( < 0.001).@*CONCLUSIONS@#Both aging and a high WFNS grade at admission are associated with a poor prognosis of aSAH, for which aneurysm clipping and coiling have similar long- term outcomes, but for patients with a high WFNS score, aneurysm clipping is favored over coiling in terms of health economics.
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Triterpenoids have been described in Andrographis paniculata. Oleanolic acid exhibits high biological activity and is widely used in the clinic, and β-sitosterol not only has good biological activity but also plays an important physiological role in plants. However, analysis of the biosynthetic pathway of triterpenoids in Andrographis paniculata has not been reported. Here, we provide the first report of the isolation and identification of nine 2, 3-oxidosqualene cyclases (ApOSC3 to ApOSC11) from A. paniculata. The results showed that ApOSC4 represented a monofunctional synthase that could convert 2, 3-oxidosqualene to β-amyrin. ApOSC5 as a bifunctional 2, 3-oxidosqualene cyclases, could transfer 2, 3-oxidosqualene to β-amyrin and α-amyrin. ApOSC6 to ApOSC8 composed the multifunctional 2, 3-oxidosqualene cyclases that could convert 2, 3-oxidosqualene to β-amyrin, α-amyrin and one or two undetermined triterpenoids. This study provides a better understanding of the biosynthetic pathway of triterpenoids in A. paniculata, and the discovery of multifunctional 2, 3-oxidosqualene cyclases ApOSC5 to ApOSC8 of the facilitates knowledge of the compounds diversity in A. paniculata.
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This study explores responses to ketamine in patients with treatment-resistant depression (TRD) using a wearable forehead electroencephalography (EEG) device. We recruited and randomly assigned 55 outpatients with TRD into three approximately equal-sized groups (A: 0.5-mg/kg ketamine; B: 0.2-mg/kg ketamine; and C: normal saline) under double-blind conditions. The ketamine responses were measured by EEG signals and Hamilton depression rating scale scores. At baseline, the responders showed significantly weaker EEG theta power than the non-responders (p < 0.05). Compared to the baseline, the responders exhibited higher EEG alpha power but lower EEG alpha asymmetry and theta cordance post-treatment (p < 0.05). Furthermore, our baseline EEG predictor classified the responders and non-responders with 81.3 ± 9.5% accuracy, 82.1 ± 8.6% sensitivity, and 91.9 ± 7.4% specificity. In conclusion, the rapid antidepressant effects of mixed doses of ketamine are associated with prefrontal EEG power, asymmetry, and cordance at baseline and early post-treatment changes. Prefrontal EEG patterns at baseline may serve as indicators of ketamine effects. Our randomized double-blind placebo-controlled study provides information regarding the clinical impacts on the potential targets underlying baseline identification and early changes from the effects of ketamine in patients with TRD.
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Antidepressivos/uso terapêutico , Depressão/fisiopatologia , Depressão/terapia , Eletroencefalografia/métodos , Ketamina/uso terapêutico , Dispositivos Eletrônicos Vestíveis , Adulto , Diagnóstico por Computador , Feminino , Testa/fisiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE@#To study the instability of mitochondrial DNA(mt DNA) D-loop region genes in patients with Leukemia.@*METHODS@#The HV-1 and HV-2 regions of D-loop region in 24 patients with leukemia were amplificated and sequenced, then their results were compared with revised Cambridge reference sequence (rCRS) and Databank mtDB. The mutation rate was detected by SPSS 22.0 statistics software.@*RESULTS@#The total mutation rate in patients was 95.83% (23/24), the detection showed 82 mutated genes, out of which 47 (57.32%) mutated genes located in HV-1 region, 35 (42.68%) mutated genes in HV-2 region. The comparison showed that the mutation rate in untreated (UT) group and treated (T) group of AML patients was (2.37±0.82)×10 and (4.76±2.45)×10 respectively(P<0.01), the mutation rate in PR and CR groups of treated AML patients was (5.10±2.56)×10 and (4.51±2.51)×10 respectively (P<0.05), the comparison among M3 group showed that the mutation rates in UT, PR and CR groups were (2.55±0.63)×10, (5.37±3.41)×10 and (3.71±1.65)×10 respectively (P>0.05).@*CONCLUSION@#The more high mutation rate and many kinds of mutation types exist in D-loop region, suggesting that the genes in D-loop region display the more strong instability, the chemotherapy may aggravate the instability of genes in D-loop region.
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Humanos , DNA Mitocondrial , Leucemia , Mitocôndrias , Mutação , Taxa de MutaçãoRESUMO
OBJECTIVE@#To investigate the injury effect of anti-donor specific antibody (DSA) on human umbilical vein enolothelial cells (HUVEC) in NK-mediated antibody-dependent cell cytotoxity (ADCC).@*METHODS@#The peripheral blood of 10 healthy donors was colleced for allo-HSCT of AML patients diagnosed in Department of Hemology of the Tumor Hospital affiliated to Shanxi Medical University, then the peripheral blood NK cells were isolated and used as the effector cells; the HUVEC of passages 9-6 were selected and co-cultured with DSA, then the DSA-binding HUVEC were used as the target cells (CDH group), while the DSA-unbinding HUVEC were used as negative control (UDH group). After co-culture of effecor cells with target cells, the expression of IFN-γ was detected by flow cytometry and the HUVEC activity was detected by using MTT method, so as to indirectily reflect the injury effect of DSA-mediated ADCC on endothelial cells.@*RESULTS@#With the increase of effector-target (E:T) ratio, the activity of HUVEC decreased, the expression level of IFN-γ increased. Under the some effector-target ratio (1∶1, 10∶1, 20∶1), the activity of HUVEC in CDH group was significantly lower than that of UDH group, and the expression of IFN-γ was significantly higher than that of the UDH group (P<0.05).@*CONCLUSION@#DSA can damage vascular endothelial cells through the ADCC effect mediated by NK cells.
Assuntos
Humanos , Anticorpos Monoclonais , Citotoxicidade Celular Dependente de Anticorpos , Células Endoteliais , Citometria de Fluxo , Células Matadoras NaturaisRESUMO
The aim of this paper was to observe the effect of triptolide( TP) on cardiovascular function and its possible mechanism by intraperitoneal injection of bacterial lipopolysaccharide in rats with endotoxemia. Sixty male Sprague-Dawley rats were randomly divided intonormal group( NC group),endotoxemia model group( LPS group),TP low concentration intervention group( LPS + TP-L group,25 μg·kg~(-1)),TP middle concentration intervention group( LPS+TP-M group,50 μg·kg~(-1)),TP high concentration intervention group( LPS+TP-H group,100 μg·kg~(-1)) and polymyxin B group( LPS+PMX-B group,0. 2 mg·kg~(-1)). 10 mg·kg~(-1) LPS was injected intraperitoneally for 6 h to replicate the endotoxemia rat model. The rats in TP intervention groups were pre-treated 15 min before intraperitoneal injection of LPS. Rats in each group underwent total arterial intubation to measure hemodynamic parameters: heart rate( HR),left ventricular diastolic pressure( LVDP),the maximum rate of the increase/decrease of left ventricular pressure( ±dp/dtmax). The levels of BNP,CK-MB and c Tn-Ⅰ in serum and levels of TNF-α and IL-6 in plasma were detected by ELISA. The contents of p65 protein in myocardium and contents of p65,TLR4,i NOS and e NOS protein in thoracic aorta were detected by Western blot. As compared with NC group,the hemodynamic indexes in LPS group were significantly decreased; the contents of BNP,CK-MB and c Tn-Ⅰ in serum,TNF-α and IL-6 in plasma,p65 in myocardium,i NOS,e NOS,TLR4 and p65 in vascular tissues were significantly increased. As compared with LPS group,the hemodynamic indexes were significantly improved in LPS+TP-M group,LPS+TP-H group and LPS+PMX-B group; the contents of BNP,CK-MB and c Tn-Ⅰ in serum,TNF-α and IL-6 in plasma,p65 in myocardium,i NOS,e NOS,TLR4 and p65 in vascular tissues were significantly decreased in each treatment group. Triptolide has a protective effect on cardiovascular damage in a dose-dependent manner in endotoxemia rats,probably through TLR4/NF-κB p65 signaling pathway to improve endothelial function.