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OBJECTIVE To explore the antidepressant effect and potential mechanism of icariside Ⅱ （ICSⅡ） based on the GABAergic nervous system. METHODS The male Kunming mice were randomly divided into a control group （group C， 10 mice） and a modeling group （50 mice）. The depression model was induced by chronic unpredictable mild stress （CUMS） method in the modeling group. After 21 days of stimulation， the rats of modeling group were randomly divided into depression model group （NS group）， positive control group [ECS group， oxalate escitalopram 15 mg/（kg·d）] and ICSⅡ low-dose， medium-dose and high-dose groups [ICSⅡ-L group， ICSⅡ-M group， ICSⅡ-H group； ICSⅡ 10， 20， 30 mg/（kg·d）]， with 10 mice in each group. Administration groups were given relevant medicine intragastrically， once a day， for 14 consecutive days. The sugar water preference rate， total exercise distance， immobility time in tail suspension and forced swimming experiments were detected in each group. The morphology of neurons and Nissl bodies in the hippocampal CA3 region were observed； the contents of γ-aminobutyric acid （GABA） and glutamic acid （Glu）， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins （GABA A receptor α1， GABA B receptor 1， vesicular GABA transporter， glutamate decarboxylase 67， GABA membranal transporter 3） were detected in hippocampus. RESULTS Compared with group C， the sugar water preference rate and the total exercise distance significantly reduced in NS group， while the values of immobility time in the tail suspension test and forced swimming test were significantly prolonged （P＜0.05）. The morphology of neurons in the CA3 area of the hippocampus was irregular and the Nissl bodies were reduced， with a significant decrease in the number of structurally intact neurons （P＜0.05）； the content of Glu was significantly increased， while the content of GABA， GABA/Glu ratio， and the expressions of GABAergic nervous system-related proteins were significantly decreased （P＜0.05）. Compared with NS group， depression behavior in each administration group was improved， and the above indexes were mostly reversed （P＜0.05）. CONCLUSIONS ICSⅡ can improve depression behavior of depression model mice. The mechanisms may be associated with regulating the balance of GABA and Glu， increasing the synthesis， transport and release of GABA， and regulating the expressions of GABA-related receptors， so as to improve GABAergic nervous system.
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Complex systems exist widely,including medicines from natural products,functional foods,and bio-logical samples.The biological activity of complex systems is often the result of the synergistic effect of multiple components.In the quality evaluation of complex samples,multicomponent quantitative analysis(MCQA)is usually needed.To overcome the difficulty in obtaining standard products,scholars have proposed achieving MCQA through the"single standard to determine multiple components(SSDMC)"approach.This method has been used in the determination of multicomponent content in natural source drugs and the analysis of impurities in chemical drugs and has been included in the Chinese Pharmacopoeia.Depending on a convenient(ultra)high-performance liquid chromatography method,how can the repeatability and robustness of the MCQA method be improved?How can the chromatography conditions be optimized to improve the number of quantitative components?How can computer software technology be introduced to improve the efficiency of multicomponent analysis(MCA)?These are the key problems that remain to be solved in practical MCQA.First,this review article summarizes the calculation methods of relative correction factors in the SSDMC approach in the past five years,as well as the method robustness and accuracy evaluation.Second,it also summarizes methods to improve peak capacity and quantitative accuracy in MCA,including column selection and two-dimensional chromatographic analysis technology.Finally,computer software technologies for predict-ing chromatographic conditions and analytical parameters are introduced,which provides an idea for intelligent method development in MCA.This paper aims to provide methodological ideas for the improvement of complex system analysis,especially MCQA.
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Objective:To investigate the predictive value of serum cystatin C (Cys-C) and renal artery resistance index (RRI) 24 h before coronary CT angiography (CTA) examination in contrast-induced nephropathy(CIN).Methods:Sixty-four patients with coronary heart disease who received coronary CTA examination in Hebei Petro China Central Hospital from January 2020 to March 2021 were selected as the research subjects. According to the incidence of CIN after coronary CTA examination, they were divided into the case group (25 patients) and the normal group(39 patients). Serum Cys-C level was measured by automatic biochemical analyzer at 24 h before CTA examination, and RRI value was measured by color Doppler ultrasound. Risk factors of CIN after CTA examination were analyzed by Logistic regression. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of serum Cys-C, RRI and the combination of the two indexes in CIN.Results:Compared with the control group, the dosage of contrast agent, patients with hypertension, serum Cys-C level at 24 h before CTA examination and RRI value in the case group were higher than those in the normal group: (85.53 ± 16.27) ml vs. (64.37 ± 15.08) ml, 80.00%(20/25) vs. 56.41%(22/39), (1.36 ± 0.18)mg/L vs.(1.02 ± 0.21) mg/L, 0.743 ± 0.093 vs. 0.632 ± 0.081, there were statistical differences ( P<0.05). Multivariate Logistic regression analysis showed that the amount of contrast agent, hypertension, serum Cys-C level at 24 h before CTA examination and RRI value were independent risk factor for CIN after CTA examination ( P<0.05). The results of ROC curve analysis showed that serum Cys-C (>1.318 mg/L) combined with RRI value (>0.653) at 24 h before CTA examination predicted CIN with the highest area under the curve was 0.922, sensitivity was 92.5% and specificity was 81.6%. Conclusions:The incidence of CIN after CTA is related to the dosage of contrastant, hypertension, serum Cys-C level and RRI value at 24 h before CTA. The combination of Cys-C level and RRI value has a high predictive value for the occurrence of CIN.
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Objective:To study the genetic profiles of phenylalanine hydroxylase (PAH) gene mutations in neonates with phenylketonuria (PKU) in Xinjiang.Methods:From January 2015 to December 2021,neonates born and genetically diagnosed with PKU in our region were retrospectively included. The genetic profiles of different ethnic groups were analyzed and compared with PKU patients from central, northwest and northern regions of China.Results:A total of 131 neonates with PKU were enrolled, including 82 Han, 25 Hui and 20 Uyghur patients, 4 cases of other ethnic groups. 46, 20 and 14 types of pathogenic variants were detected in each ethnic group with detection rates of 95.1% (156/164), 66.0% (33/50), and 60.0% (24/40), respectively. The variants were mainly missense mutations and located in exons 2, 3, 6,7 and 11. The most common loci in Hui patients were c.158G>A (18.2%), c.728G>A (18.2%) and c.898G>T (9.1%). The most common loci in Uyghur patients were c.158G>A (33.3%), c.355C>T (12.5%) and c.1068C>A (8.3%). c. 898G>T might be most unique in Hui patients and c.355C>T most unique in Uyghur patients in Xinjiang. A novel variant of PAH gene, c.828G>C (p.M276I) in exon 7 was identified. Compared with northern, central and northwestern regions of China, PKU patients in Xinjiang had significantly higher incidence of c.158G>A mutation and lower incidence of c.728G>A mutation ( P<0.05). Conclusions:Missense mutations of PAH gene are common in some regions of Xinjiang. The compositions of PAH gene variations are similar to northwest and northern China with significant differences in hotspots of mutations.
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Objective:To summarize the clinical characteristics of cardiomyopathy with coronary artery disease in children and explore the application value of multi-slice spiral CT coronary angiography(MSCTA) in the diagnosis and treatment of cardiomyopathy in children.Methods:Patients diagnosed with cardiomyopathy who were hospitalized in the Department of Cardiology at Beijing Children′s Hospital from January 2016 to December 2022 and had complete cardiac imaging data were selected as the study subjects.The demographic characteristics, general clinical and cardiac imaging data of the patients were collected for systematic retrospective analysis.Results:Among 93 patients included in this study, dilated cardiomyopathy was the most common(34.4%, 32/93). MSCTA detected 17 cases(18.3%, 17/93) of high coronary opening, ten cases (10.8%, 10/93) of myocardial bridge, and nine cases (9.7%, 9/93) of coronary disease were detected by echocardiography.Compared with echocardiography, MSCTA had a higher detection rate of abnormal coronary artery origin and myocardial bridge, and the difference was statistically significant( P<0.05). Conclusion:Children′s cardiomyopathy can be complicated with coronary artery disease.MSCTA has great application value in the diagnosis of coronary artery disease.
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Objective:To describe the clinical features and prognosis of congenital anomalous origin of coronary artery(AOCA) in children to increase our understanding of the disease.Methods:This retrospective study included children diagnosed with AOCA using computed tomography coronary angiography(CTCA) admitted to the Department of Cardiology, Beijing Children′s Hospital, Capital Medical University, from January 1, 2014 to December 31, 2019.The clinical presentations, laboratory results, imaging analyses, treatments, and prognoses of these patients were analyzed.Results:A total of 208 children, including 105 boys and 103 girls, we evaluated the ages(9.03±4.18)years old with AOCA.Of these, 157 cases(75.5%) presented with cardiac symptoms, such as chest tightness, palpitations, dizziness, syncope, fatigue, and decreased endurance.Three cases(1.4%) had atypical symptoms of paroxysmal crying, dyspnoea and cyanosis, and 48 cases(23.1%) were asymptomatic.Levels of serological markers of myocardial injury were elevated in 59 cases(28.4%), and 140 cases(67.3%) had predominant ST-T abnormalities on electrocardiograms.Transthoracic echocardiography identified 27 cases (13%) with cardiac enlargement and ten cases(4.8%) with left ventricular systolic dysfunction.There were 126 cases(60.6%) with the anomalous origin of the left coronary artery revealed by CTCA, 50 cases(24.0%) with the anomalous origin of the right coronary artery and 32 cases(15.4%) with bilateral coronary arteries of anomalous origin.Five children underwent surgical treatment, and the remaining 203 children were treated conservatively with drugs.The whole group was successfully treated, and no death case was recorded during the follow-up period.Conclusion:AOCA may cause different degrees of myocardial ischemia.Diverse clinical presentations and diagnostic limitations of transthoracic echocardiography often lead to missed diagnosis or misdiagnosis.In contrast, CTCA has high diagnostic accuracy and can be used to identify the location and course of the coronary ostia.Hence, the management of AOCA should be tailored on a case-to-case basis, taking into consideration of the specific type of coronary origin, with surgical intervention being warranted if necessary.
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Objective:To investigate the current status of women′s level of birth experience and lactation initiation time and explore the effect of level of birth experience on lactation initiation time.Methods:This was a cross-sectional study. A convenience sampling method was used to select 622 maternal cases attending the Affiliated Hospital of Jining Medical College from November, 2020 to January, 2021, and the distribution of their labor experience level and lactation initiation time was investigated by questionnaire and follow-up assessment.Results:There were 622 women with transvaginal deliveries who had lactation initiation times of more than 72 h in 241 cases (38.75%). The scores for each dimension of the Childbirth Experience Questionnaire (CEQ) were (49.63 ± 8.58)points, and the scores for each dimension of CEQ were perceived safety, professional support, involvement and self-efficacy in descending order. The results of the correlation analysis showed that there was a negative correlation between the scores on each dimension of CEQ and the total score and lactation initiation time ( r values were -0.436 to -0.146, all P<0.01). Stratified regression analysis showed that after controlling for age, number of births, gestational weeks of labour, illness during pregnancy and labour analgesia as the underlying variables affecting lactation initiation time, the scores for self-efficacy, involvement, perceived safety and professional support in the CEQ all affected lactation initiation time after delivery ( t values were -6.76 to -2.02, all P<0.05). Conclusions:The birth experience and lactation of women who deliver via vaginal birth need to be taken into account. The more negative the birth experience, the longer the lactation initiation time. The women′s involvement in the birth process, their own competence, perceived safety and level of professional support are all valid influencing indicators of lactation initiation time.
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Objective:To investigate the effects of Tiaogan Lifei Decoction on the level of symptom control in patients with bronchial asthma (asthma) treated with moderate and high dosage inhaled glucocorticoids (ICS).Methods:Randomized double-blind placebo controlled prospective study was used. Totally 90 patients with asthma (liver lung disharmony, wind phlegm blocking collateral syndrome) using moderate and high dosage ICS who met the inclusion criteria from January 2020 to December 2021 in Chaoyang District Hospital of Traditional Chinese Medicine in Beijing were divided into two groups according to random number table method, with 45 cases in each group. On the basis of using the original dosage of ICS, the treatment group used Tiaogan Lifei Decoction, while the control group used Tiaogan Lifei Decoction simulant. The course of treatment was 12 weeks. TCM symptom score of both group before and after the treatment was detected; asthma control test (ACT) was used to assess the effects of asthma on the patients; St George's Hospital Respiratory Questionnaire (SGRQ) was used to assess patients' quality of life; the peak expiratory flow rate (PEF) was measured with a peak expiratory flow meter. 2 ml of venous blood was collected for eosinophil (EOS) detection, and the serum allergen specific IgE level was determined by ELISA. The adverse reactions were observed during the treatment and the clinical efficacy was evaluated.Results:During the test, 3 cases and 2 cases in the treatment group and control group lost prevention respectively. 3 cases in the treatment group and 6 cases in the control group withdrew from the trial because of the aggravation of symptoms and the need to increase the dosage of ICS. The total effective rate in the treatment group was 78.6% (33/42), and that in the control group was 55.8% (24/43), with statistical significance ( χ2=4.98, P=0.026). After treatment, the scores of daily activities, early awakening, control and total scores in the treatment group were higher than those in the control group ( t values were 1.76, 1.99, 2.00, 2.69, respectively, P<0.01 or P<0.05); after treatment, the scores of cough, chest tightness, active wheezing, upset, pharyngeal itch and total score in the treatment group were lower than those in the control group ( t values were -5.89, -6.01, -5.66, -4.27, -6.67, -9.05, respectively, P<0.01); SGRQ score in the treatment group was lower than that of the control group ( t=-7.19, P<0.01). No serious adverse reactions occurred during treatment in the two groups. Conclusion:Tiaogan Lifei Decoction is helpful to improve the symptom control level of asthma patients who are using ICS, and effectively improve the quality of life of patients with asthma of liver lung disharmony and wind phlegm obstructing collaterals syndrome.
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Objective:To explore the efficacy of subcutaneous injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in preventing invasive fungal disease (IFD) in patients with multiple myeloma (MM).Methods:The clinical data of 222 patients who were admitted to the Second Hospital of Harbin Medical University from January 2015 to June 2021 were retrospectively analyzed. The patients was given GM-CSF (3-5 μg·kg -1·d -1, GM-CSF group) or granulocyte colony-stimulating factor (G-CSF, 2-5 μg·kg -1·d -1, G-CSF group) when neutrophils (ANC) ≤1.5×10 9/L after induction chemotherapy. Patients were discontinued when white blood cell count (WBC) ≥10.0×10 9/L. The incidence of IFD (including confirmed, clinical and proposed diagnosis) and breakthrough invasive fungal infections was compared between the two groups. Results:The incidence of IFD was 8.1% (18/222) in all patients. The incidence of IFD was 3.5% (3/85) and 10.9% (15/137) in the GM-CSF and G-CSF groups, respectively, and the difference between the two groups was statistically significant ( χ2 = 3.88, P = 0.049). In 9 patients of GM-CSF group receiving fungal infection prophylaxis and in 15 patients of G-CSF group receiving fungal infection prophylaxis, the incidence of breakthrough invasive fungal infections was 0 and 7 cases, respectively, and the difference between the two groups was statistically significant ( P = 0.022). Conclusions:GM-CSF application in MM patients can reduce the incidence of IFD and breakthrough invasive fungal infections.
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ObjectiveTo understand the changes of health related behaviors among residents with chronic diseases，and to provide a reference for targeted health intervention. MethodsBased on the surveillance data of chronic diseases and relevant risk factors of the residents in Huangpu District from 2014 to 2019. The study focused on health related behaviors and sociodemographic characteristics which was analyzed by chi-square test. The Cochran-Armitage trend chi-squared test was used to analyze the standardization rate. ResultsSeveral behaviors had been ameliorated such as the health examinations （Z=-3.667， P<0.001）， the measurement of blood glucose （Z=-5.793， P<0.001）， daily vegetables consumption （Z=-5.741， P<0.001）， daily animal food consumption （Z=-23.214， P<0.001）， daily physical activity （Z=-18.361， P<0.001）， sedentary behavior （Z=4.190， P<0.001）， and current smoking （Z=4.615， P<0.001）. ConclusionAn improving trend of health behaviors is found among Huangpu District residents．Targeted health education and health promotion should be carried out according to the characteristics of the population in the future.
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Exosomes are nanoscale extracellular vesicles that are secreted by a variety of cells in the body. They carry particular miRNA, protein molecules, transcription factors, and other information molecules, and they play a role in the pathophysiological regulation of a number of diseases in the body. Exosomes can persist steadily in biological tissues and bodily fluids. Exosomes have quickly advanced in ophthalmology in recent years due to the extensive studies of exosomes in a variety of fields, such as diabetic retinopathy, age-related macular degeneration, autoimmune uveitis, corneal disease, glaucoma, and other diseases. The number of people who are blind caused by diabetic retinopathy is rising as living standards rise. However, it is still unclear how diabetic retinopathy works. In recent years, many studies have found that exosomes play an important role in diabetic retinopathy. In this paper, the most recent developments in exosome studies as they relate to the pathogenesis and progression of diabetic retinopathy are reviewed.
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Objective: Analysis and investigation of pathogenic characteristics of polymyxin-and carbapenem-resistant Klebsiella pneumoniae (PR-CRKP). Methods: A total of 23 PR-CRKP strains isolated from clinical specimens from the General Hospital of Southern Theater Command from March 2019 to July 2021 were retrospectively collected, Whole-genome sequencing was performed on 23 PR-CRKP strains, resistance genes were identified by comparison of the CARD and the ResFinder database, high-resolution typing of PR-CRKP strains was analyzed by core genomic multilocus sequencing (cgMLST) and single nucleotide polymorphism (SNP); polymyxin resistance genes were determined by PCR and sequencing. Results: All PR-CRKP strains were KPC-2 producing ST11 types. cgMLST results showed that the evolutionary distance between the PR-CRKP strains and Klebsiella pneumoniae in mainland China was 66.44 on average, which is more closely related than foreign strains; the 23 PR-CRKP strains were divided into 3 main subclusters based on SNP phylogenetic trees, with some aggregation among Clade 2-1 in the isolation department and date. The two-component negative regulatory gene mgrB has seven mutation types including point mutations, different insertion fragments and different insertion positions. Conclusion: The close affinity of PR-CRKP strains indicate the possibility of nosocomial clonal transmission and the need to strengthen surveillance of PR-CRKP strains to prevent epidemic transmission of PR-CRKP.
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Humans , Carbapenems/pharmacology , Anti-Bacterial Agents/therapeutic use , Klebsiella pneumoniae/genetics , Polymyxins/pharmacology , beta-Lactamases , Phylogeny , Retrospective Studies , Multilocus Sequence Typing , Microbial Sensitivity TestsABSTRACT
ObjectiveTo construct a framework of PICO for occupational therapy to improve upper extremity function in stroke patients based on World Health Organization Family of International Classifications (WHO-FICs), and to analyze the functional outcome of major occupational therapies to improve upper extremity in stroke. MethodsUsing the WHO-FICs framework, the databases such as Web of Science, PubMed, CNKI and SinoMed were searched for literature related to occupational therapy interventions for upper extremity function in stroke patients from the date of establishment to October, 2022, and the contents of the literature were extracted for a systematic review. ResultsTen randomized controlled trials from six countries were finally included, involving 382 participants (≥ 18 years old). The literatures were mainly from the fields of rehabilitation medicine, physics and rehabilitation medicine, neuroscience, bioengineering medicine, occupational therapy and other research fields, and were published mainly after 2013. The quality of the included literatures was evaluated using Physiotherapy Evidence Database (PEDro) scale with a mean score of 7.5. Based on the WHO-FICs framework, the types of diseases included intracerebral haemorrhage (8B00), cerebral ischemic stroke (8B11), subarachnoid hemorrhage (8B01), abnormality of tonus and reflex (MB47), and hemiplegia (MB53). The main dysfunctions of the upper extremity after stroke included mobility of joint functions (b710), stability of joint functions (b715), muscle power functions (b730), muscle tone functions (b735), motor reflex functions (b750), control of voluntary movement functions (b760), involuntary movement functions (b765). Activity and participation included activity of upper limb, such as lifting and carrying objects (d430), hand and arm use (d445), and fine hand use (d440); and the daily life activities and social participation, such as self-care (d510-d570), domestic life (d610-d660), major life areas (d810-d879), community, social and civic life (d910-d950). Therapeutic interventions on body functions included electrical stimulation of muscle functions (MU2.SC.BP), assistance and guidance of exercise for involuntary movement reaction (MV2.PG.ZZ); therapeutic interventions involving activity and participation were training in lifting and carrying (SIA.PH.ZZ), training in fine hand use (SIG.PH.ZZ), exercises of arm and hand use (SIJ.PH.ZZ), self care (SM1-SMH), household tasks (SO2-SOD), and playing games (SXD.PH.ZZ); 15 to 60 minutes a time, three to ten times a week, for three to eight weeks, in hospital or at home. The outcomes of the intervention were divided into three levels. At the body function level, patients had improved neuromotor conduction function, reflex function, casual motor control, coordination and speed, joint mobility, and grip strength. At the activity and participation level, there were enhancements in upper limb mobility and speed, fine hand function and speed, frequency and quality of upper limb activity participation, and the capacities of daily living and reduced difficulty in daily activity tasks. In terms of whole functioning, patients had acquired quality of life and well-being and acquainted a feeling of pleasure and accomplishment. ConclusionA PICO framework was constructed for occupational therapy based on WHO-FICs. The health conditions included intracerebral haemorrhage, cerebral ischemic stroke, subarachnoid hemorrhage, abnormality of tonus and reflex, and hemiplegia. Upper extremity motor dysfunction mainly included dysfunction of voluntary motor control, low or hyperactive motor reflexes, abnormalities in muscle tone, impaired muscle coordination, poor stability of joint activities, and reduced muscle strength, etc. Activity limitation and participation restriction were manifested as functioning in the fields of arm and hand activity participation, fine manual activity, and activities of daily living and social participation. Therapeutic interventions at body function level included brain-computer interface-based functional electrical stimulation and unimanual mirror therapy; therapeutic interventions at activity and participation level included action observation training, bimanual mirror therapy, task-oriented training, bilateral arm training and upper extremity robotics training. The health and functional benefits included the improvements in upper extremity motor function, upper extremity mobility and participation levels, activities of daily living and social participation, and quality of life and well-being.
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ObjectiveTo analyze the risk factors for in-hospital mortality in patients with Takotsubo Syndrome （TTS）. MethodsHospitalization data of consecutive patients with TTS from February 2009 to January 2022 were retrospectively collected and analyzed. Patients were divided into survival group and death group according to outcomes. The basic clinical information， triggering factors， laboratory examinations， electrocardiogram， echocardiography， complications and treatments of the two groups were compared. Univariable logistic regression analysis was used to screen the possible risk factors for in-hospital mortality in TTS patients， and multivariable logistic regression analysis was used to determine the independent risk factors for in-hospital mortality in TTS patients. ResultsA total of 62 TTS patients were included in our study， including 21 males （33.9%）， 41 females （66.1%） and 26 postmenopausal women （41.9%）， with the mean age of （55.6±16.2） years， and physical triggers were found in 50 patients （80.6%）. 17 patients （27.4%） died while 45 patients （72.6%） survived during hospitalization. The death group had lower systolic blood pressure and left ventricular ejection fraction （LVEF）， higher incidence rate of syncope， higher level of N-terminal pro-B natriuretic peptide （NT-proBNP） and hypersensitive troponin T （hs TnT） when compared with survival group （all P value <0.05）. As for the triggering factors， the proportion of TTS induced by neurologic disorders in the death group was higher than that in the survival group （P<0.05）. The death group had higher rates of cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， and respiratory failure （all P value <0.05）. Compared with the survival group， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were higher in the death group （all P value <0.05）. Univariable logistic regression analysis suggested that syncope， NT-proBNP， LVEF， neurologic disorders， cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， respiratory failure， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were potential risk factors for in-hospital mortality in TTS patients （all P value <0.05）. Multivariable logistic regression analysis indicated that neurologic disorders ［OR（95%CI）=5.651（1.195，26.715），P=0.029］， atrial fibrillation ［OR（95%CI）=6.217（1.276，30.298）， P=0.024）］ and therapeutic norepinephrin ［OR（95%CI）=8.847（1.912，40.949）， P=0.005］ were independent risk factors for in-hospital mortality in TTS patients. ConclusionsNeurologic disorders， atrial fibrillation and therapeutic norepinephrin are independent risk factors for in-hospital mortality in patients with Takotsubo Syndrome. Clinically， attention should be paid to the prevention and treatment of neurologic disorders and atrial fibrillation； norepinephrine should be carefully used in patients with diagnosed TTS complicated with hemodynamic instability.
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Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8+ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.
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Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.
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Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T+tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.
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Mice , Animals , NF-kappa B , Myeloid Differentiation Factor 88/metabolism , Lipopolysaccharides/pharmacology , Toll-Like Receptor 4/metabolism , Autistic Disorder/metabolism , Signal Transduction/physiologyABSTRACT
OBJECTIVE@#To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome.@*METHODS@#In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded.@*RESULTS@#From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05).@*CONCLUSION@#Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).
Subject(s)
Humans , Paroxetine/adverse effects , Spleen , Anxiety , Syndrome , Medicine, Chinese Traditional , Treatment Outcome , Double-Blind MethodABSTRACT
BACKGROUND@#Weather conditions are a possible contributing factor to age-related macular degeneration (AMD), a leading cause of irreversible loss of vision. The present study evaluated the joint effects of meteorological factors and fine particulate matter (PM2.5) on AMD.@*METHODS@#Data was extracted from a national cross-sectional survey conducted across 10 provinces in rural China. A total of 36,081 participants aged 40 and older were recruited. AMD was diagnosed clinically by slit-lamp ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (OCT). Meteorological data were calculated by European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and were matched to participants' home addresses by latitude and longitude. Participants' individual PM2.5 exposure concentrations were calculated by a satellite-based model at a 1-km resolution level. Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the joint effects of meteorological factors and PM2.5 on AMD.@*RESULTS@#The prevalence of AMD in the study population was 2.6% (95% CI 2.42-2.76%). The average annual PM2.5 level during the study period was 63.1 ± 15.3 µg/m3. A significant positive association was detected between AMD and PM2.5 level, temperature (T), and relative humidity (RH), in both the independent and the combined effect models. For PM2.5, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) across increasing quartiles were 0.828 (0.674,1.018), 1.105 (0.799,1.528), and 2.602 (1.516,4.468). Positive associations were observed between AMD and temperature, with ORs (95% CI) of 1.625 (1.059,2.494), 1.619 (1.026,2.553), and 3.276 (1.841,5.830), across increasing quartiles. In the interaction analysis, the estimated relative excess risk due to interaction (RERI) and the attributable proportion (AP) for combined atmospheric pressure and PM2.5 was 0.864 (0.586,1.141) and 1.180 (0.768,1.592), respectively, indicating a synergistic effect between PM2.5 and atmospheric pressure.@*CONCLUSIONS@#This study is among the first to characterize the coordinated effects of meteorological factors and PM2.5 on AMD. The findings warrant further investigation to elucidate the relationship between ambient environment and AMD.
Subject(s)
Humans , Adult , Middle Aged , Cross-Sectional Studies , Air Pollutants/analysis , Particulate Matter/analysis , China/epidemiology , Macular Degeneration/etiology , Meteorological ConceptsABSTRACT
OBJECTIVE@#This study aimed to investigate the association of ambient PM2.5 exposure with blood pressure (BP) at the population level in China.@*METHODS@#A total of 14,080 participants who had at least two valid blood pressure records were selected from the China Health and Retirement Longitudinal Survey during 2011-2015. Their long-term PM2.5 exposure was assessed at the geographical level, on the basis of a regular 0.1° × 0.1° grid over China. A mixed-effects regression model was used to assess associations.@*RESULTS@#Each decrease of 10 μg/m3 in the 1 year-mean PM2.5 concentration (FPM1Y) was associated with a decrease of 1.24 [95% confidence interval (CI): 0.84-1.64] mmHg systolic BP (SBP) and 0.50 (95% CI: 0.25-0.75) mmHg diastolic BP (DBP), respectively. A robust association was observed between the long-term decrease in PM2.5 and decreased BP in the middle-aged and older population. Using a generalized additive mixed model, we further found that SBP increased nonlinearly overall with FPM1Y but in an approximately linear range when the FPM1Y concentration was < 70 µg/m3; In contrast, DBP increased approximately linearly without a clear threshold.@*CONCLUSION@#Efficient control of PM2.5 air pollution may promote vascular health in China. Our study provides robust scientific support for making the related air pollution control policies.