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OBJECTIVES: To observe the clinical efficacy of the spirit-regulation method of Jin's three-needle therapy on post-stroke anxiety and its effects on the hypothalamus-pituitary-adrenal (HPA) axis. METHODS: Fifty-four patients with post-stroke anxiety were divided into spirit regulation (Jin's three needle therapy) group and sham-acupuncture group according to the random number table method, 28 cases in the spirit regulation and 26 cases in the sham-acupuncture group. The patients of the two groups received the same regimen of basic medication and rehabilitation, and the same acupoint prescription was adopted, including Sishenzhen (extra points, 1.5 cun to Baihui ï¼»GV20ï¼½ at 3, 6, 9 and 12 o'clock positions), Shenting (GV24), Yintang (EX-HN3), and bilateral Shenmen (HT7), Sanyinjiao (SP6), Hegu (LI4) and Taichong (LR3). The true acupuncture was delivered in the spirit regulation group and the sham acupuncture operated in the sham-acupuncture group. One treatment lasted for 30 min, once daily, 5 times a week. The duration of treatment was 3 weeks in the trial. Before treatment and on day 10 and day 21 of treatment, the changes in the score of Hamilton anxiety scale (HAMA) and that of National Institutes of Health Stroke Scale (NIHSS) were compared between the two groups separately. Using ELISA, the contents of adrenocorticotropin (ACTH) and cortisol (CORT) in the serum were detected, and the adverse reactions were recorded. RESULTS: In the within-group comparison before and after treatment, HAMA score and NIHSS score dropped on day 10 and day 21 after treatment in the spirit regulation group (P<0.05)ï¼HAMA score and NIHSS score in the sham-acupuncture group were decreased on day 21 of treatment (P<0.05). After 21 days of treatment, HAMA score and NIHSS score in the spirit-regulation group were decreased significantly than those in the sham-acupuncture group (P<0.05) and the contents of ACTH and CORT in the serum decreased when compared with those before treatment and those of the sham-operation group (P<0.05). No obvious adverse events occurred in the spirit-regulation group and the sham-acupuncture group. CONCLUSIONS: Using sham acupuncture as a control, it is preliminarily confirmed that the spirit regulation method of Jin's three-needle therapy is effective on post-stroke anxiety. In association of the downtrend of serological indicators, it is speculated that the underlying mechanism of this therapy is related to HPA axis.
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Terapia por Acupuntura , Acidente Vascular Cerebral , Humanos , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Terapia por Acupuntura/métodos , Ansiedade/terapia , Resultado do Tratamento , Pontos de Acupuntura , Hormônio AdrenocorticotrópicoRESUMO
OBJECTIVE: To observe the effect of standardized Jin's three-needle therapy on limb motor function and nerve function defect in stroke patients, and to evaluate the placebo control method. METHODS: A total of 66 patients with stroke were randomly divided into a Jin's three-needle group (33 cases, 3 cases dropped off) and a placebo needle group (33 cases, 4 cases dropped off). All the patients were treated with conventional medication and rehabilitation treatment. In addition, the patients in the Jin's three-needle group were treated with standardized Jin's three-needle therapy at temporal three points, spirit four points, hand three points, foot three points, upper extremity spasm three points, lower extremity spasm three points, etc.; while the patients in the placebo needle group were treated with placebo needling at identical points. All the treatments were given once a day, 5 days a week, and 3-week treatment was given with an interval of 2 days between weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were observed before treatment, 10 d and 21 d into treatment, and the blind evaluation was conducted after treatment. RESULTS: On the 10 d and 21 d into treatment, the FMA scores in both groups were higher than those before treatment (P<0.01), and the NIHSS scores were lower than those before treatment (P<0.01). On the 10 d and 21 d into treatment, the FMA scores in the Jin's three-needle group were higher than those in the placebo needle group (P<0.05); on the 10 d into treatment, the NIHSS score in the Jin's three-needle group was were lower than that in the placebo needle group (P<0.05). There was no significant difference between the two groups on judging the type of treatment (P>0.05), and the consistency with the real situation was poor (Cohen's kappa coefficient<0.20). CONCLUSION: The standardized Jin's three-needle therapy could effectively improve the limb motor function and nerve function defect in stroke patients. The placebo control method used in this study shows good clinical operability and masking effect.
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Terapia por Acupuntura , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Terapia por Acupuntura/métodos , Pontos de Acupuntura , Acidente Vascular Cerebral/terapia , Extremidade Inferior , Agulhas , Resultado do TratamentoRESUMO
OBJECTIVE@#To observe the effect of standardized Jin's three-needle therapy on limb motor function and nerve function defect in stroke patients, and to evaluate the placebo control method.@*METHODS@#A total of 66 patients with stroke were randomly divided into a Jin's three-needle group (33 cases, 3 cases dropped off) and a placebo needle group (33 cases, 4 cases dropped off). All the patients were treated with conventional medication and rehabilitation treatment. In addition, the patients in the Jin's three-needle group were treated with standardized Jin's three-needle therapy at temporal three points, spirit four points, hand three points, foot three points, upper extremity spasm three points, lower extremity spasm three points, etc.; while the patients in the placebo needle group were treated with placebo needling at identical points. All the treatments were given once a day, 5 days a week, and 3-week treatment was given with an interval of 2 days between weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were observed before treatment, 10 d and 21 d into treatment, and the blind evaluation was conducted after treatment.@*RESULTS@#On the 10 d and 21 d into treatment, the FMA scores in both groups were higher than those before treatment (P<0.01), and the NIHSS scores were lower than those before treatment (P<0.01). On the 10 d and 21 d into treatment, the FMA scores in the Jin's three-needle group were higher than those in the placebo needle group (P<0.05); on the 10 d into treatment, the NIHSS score in the Jin's three-needle group was were lower than that in the placebo needle group (P<0.05). There was no significant difference between the two groups on judging the type of treatment (P>0.05), and the consistency with the real situation was poor (Cohen's kappa coefficient<0.20).@*CONCLUSION@#The standardized Jin's three-needle therapy could effectively improve the limb motor function and nerve function defect in stroke patients. The placebo control method used in this study shows good clinical operability and masking effect.
Assuntos
Humanos , Terapia por Acupuntura/métodos , Pontos de Acupuntura , Acidente Vascular Cerebral/terapia , Extremidade Inferior , Agulhas , Resultado do Tratamento , Reabilitação do Acidente Vascular CerebralRESUMO
BackgroundChronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease, and patients with COPD often experience substantially emotional difficulties, such as anxiety and depression, all of which may cause serious detriment to the prognosis of patients. As a non-pharmacological intervention in clinical practice, group mindfulness-based stress reduction therapy (MBSR) is beginning to emerge, while has rarely been studied in COPD patients with concurrent emotional difficulties. ObjectiveTo evaluate the effects of group MBSR on depression, state of mindfulness and pulmonary function in stable COPD patients, so as to provide references for the application of group MBSR in patients with COPD. MethodsA total of 97 patients with stable COPD who were followed up in the Department of Respiratory and Critical Care Medicine of Mianyang Third People's Hospital from January to October 2019 were selected as the study objects, and they were assigned into study group (n=50) and control group (n=47) by random number table method. All individuals received routine medication therapy and an 8-week health education, based on this, participants in study group partook an 8-week intervention comprising group MBSR. At the baseline, 4 weeks and 8 weeks of intervention, participants were assessed with Self-rating Depression Scale (SDS), Five Facet Mindfulness Questionnaire (FFMQ) and COPD Assessment Test (CAT), as well as the pulmonary function testing. ResultsThere were 41 patients in study group and 42 cases in control group completed the study. The group * time interaction was interpreted as significant between two groups for SDS, FFMQ and CAT scores (F=54.858, 86.161, 69.862, P<0.01). Baseline SDS, FFMQ and CAT scores of the two groups yielded no statistical difference between two groups (F=0.240, 0.052, 0.019, P>0.05), while study group scored lower on SDS and CAT (F=12.900, 38.511, 7.797, 28.824, P<0.01) and higher on FFMQ (F=27.324, 82.412, P<0.01) than those of the control group after 4 and 8 weeks of intervention. With the prolongation of intervention time in study group, participants demonstrated an overall reduction in SDS and CAT scores (F=109.753, 124.144, P<0.01), and an increase in FFMQ scores (F=228.194, P<0.01). There were no between-group differences in forced expiratory volume in one second as percentage of predicted volume (FEV1%pred) after 4 and 8 weeks of intervention (F=0.104, P=0.748) , and the within-group changes in FEV1%pred value over the intervention period in study group was not statistical (F=0.561, P=0.458). ConclusionGroup MBSR may help relieve depressive symptoms, enhance mindfulness level, and alleviate clinical symptoms in stable COPD patients, but has no effect on pulmonary function. [Funded by Mianyang Health and Health Commission Scientific Research Project (number, 201916)]
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Background: Cesarean delivery vs vaginal delivery was reported to increase the risks of childhood obesity, pneumonia, anemia, and neurobehavioral disorders, but few studies were able to deal with the confounding biases associated with medical conditions indicating cesareans. This prospective cohort study aims to investigate the associations of non-medically indicated cesarean delivery on maternal request (CDMR) with these child health outcomes. Methods: Among 17 748 liveborn infants whose mothers (primiparas) participated in a randomized controlled trial on micronutrient supplementation and pregnancy outcomes during 2006-2009 in 5 rural counties in Hebei Province, China, 6972 singletons born by full-term spontaneous vaginal delivery (SVD) and 3626 by CDMR were extracted for the assessments of obesity (weight-for-height z-score >3) and pneumonia (self-reported) at 1.5-5 years in 2011. Some children were further randomly selected from these two groups for the assessments of anemia (hemoglobin <110 g/L, 2341 SVD and 2417 CDMR) and neurobehavioral disorders (raw score of Child Behavior Checklist larger than the 90th percentile of the normative sample, 1257 SVD and 1060 CDMR). Results: Compared with SVD, CDMR was associated with increased risks of obesity (adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) = 1.14-1.75, P = 0.002) and anemia (aOR = 1.65, 95% CI = 1.28-2.12, P < 0.001), but not with the risk of pneumonia (aOR = 1.16, 95% CI = 0.94-1.45, P = 0.17) or neurobehavioral disorders (aORs varied from 0.82 to 0.91, P > 0.05) in childhood. Conclusions: Cesarean delivery, independent of cesarean indications, is likely associated with childhood obesity and anemia, indicating a need to keep pregnant women informed, especially those seeking CDMR, a need to explore possible improvement on obstetric service, and even a need for main stakeholders to reach a compromise in making a cesarean decision. Trial registration: ClinicalTrials.gov: NCT00133744 and NCT01404416.
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Saúde da Criança , Obesidade Infantil , Cesárea , Criança , Parto Obstétrico , Feminino , Humanos , Lactente , Obesidade Infantil/epidemiologia , Gravidez , Estudos ProspectivosRESUMO
Mecicinal plants boast abundant natural compounds with significant pharmacological activity, and such compounds, featuring diversified and complex structures, can be used for research and development of drugs. At present, these natural compounds are directly extracted from herbs which, however, suffer from damaged wild resources and shortage of planting resources attributing to the increasing demand. Moreover, the low content in medicinal plants and complex structures are another challenge to the research and development of drugs. Heterologous synthesis with synthetic biology methods is a solution that has attracted wide attention. Synthetic bio-logy for the production of natural active compounds in Chinese medicinal plants involves the exploration of key enzymes in compound bio-synthetic pathways from plants, analysis of enzyme functions and mechanisms, and reconstruction and optimization of biosynthetic pathways in microorganisms for efficient synthesis of compounds. This study briefed the development process of synthetic biology and the biosynthetic pathways of terpenoids, alkaloids, and flavonoids, and summarized the related strategies of synthetic biology such as the reconstruction and optimization of metabolic pathways, regulation of fermentation process, and strain improvement, and the latest applications of heterogeneous synthetic biology in the production of natural compounds from Chinese medicinals. This study is expected to serve as a reference for the efficient production of terpenoids, alkaloids, flavonoids, and other active compounds from Chinese medicinal plants with strategies of synthetic biology.
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Alcaloides , Plantas Medicinais , Vias Biossintéticas , China , Biologia SintéticaRESUMO
The most frequent missense mutations in familial Parkinson's disease (PD) occur in the highly conserved LRRK2/PARK8 gene with G2019S mutation. We previously established a fly model of PD carrying the LRRK2-G2019S mutation that exhibited the parkinsonism-like phenotypes. An herbal medicine, Gastrodia elata Blume (GE), has been reported to have neuroprotective effects in toxin-induced PD models. However, the underpinning molecular mechanisms of GE beneficiary to G2019S-induced PD remain unclear. Here, we show that these G2019S flies treated with water extracts of GE (WGE) and its bioactive compounds, gastrodin and 4-HBA, displayed locomotion improvement and dopaminergic neuron protection. WGE suppressed the accumulation and hyperactivation of G2019S proteins in dopaminergic neurons and activated the antioxidation and detoxification factor Nrf2 mostly in the astrocyte-like and ensheathing glia. Glial activation of Nrf2 antagonizes G2019S-induced Mad/Smad signaling. Moreover, we treated LRRK2-G2019S transgenic mice with WGE and found that the locomotion declines, the loss of dopaminergic neurons, and the number of hyperactive microglia were restored. WGE also suppressed the hyperactivation of G2019S proteins and regulated the Smad2/3 pathways in the mice brains. We conclude that WGE prevents locomotion defects and the neuronal loss induced by G2019S mutation via glial Nrf2/Mad signaling, unveiling a potential therapeutic avenue for PD.
Parkinson's disease is a brain disorder that leads to tremors and difficulties with balance and coordination. These symptoms are caused by the loss of neurons which release a chemical messenger that is needed to regulate movement called dopamine. Most treatments for this disease work by boosting levels of dopamine in the brain, but this can lead to severe side effects and these drugs often become less effective over time. A traditional Chinese medicine called Gastrodia elata Blume (or GE for short) has previously been reported to relieve symptoms of Parkinson's disease in both human and animal studies when administered as a decoction or formula. However, it is unclear how GE protects dopamine-producing neurons and if this mechanism involves another type of brain cell known as glia that has also been linked to Parkinson's disease. To investigate, Lin et al. studied fruit flies and mice that carry a genetic mutation that produces the symptoms and molecular characteristics of Parkinson's disease. The experiments showed that when the flies and mice were fed food containing water extracts of GE, they experienced less difficulties moving and had a higher number of intact dopamine-producing neurons. Lin et al. found that GE switched on a protein in glial cells located near dopamine-producing neurons. Activation of this protein, called Nrf2, inhibited a signaling pathway in degenerating neurons that leads to the disease state. As a result, less dopamine-producing neurons were damaged and the animals' coordination and balance were maintained. These findings suggest that GE could potentially provide an alternative or complementary therapy for Parkinson's disease, although it still needs to be studied further in humans. If the same effect is observed, the specific compounds in GE that have this protective effect could be isolated and analyzed to see if they could be used for treatment.
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Gastrodia/química , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/farmacologia , Transdução de Sinais , Animais , Álcoois Benzílicos/farmacologia , Butiratos/farmacologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Drosophila melanogaster , Glucosídeos/farmacologia , Locomoção/efeitos dos fármacos , Camundongos , Neuroglia/fisiologia , NeuroproteçãoRESUMO
To analyze the outcome indicators from the randomized controlled trials(RCTs) on traditional Chinese medicine(TCM) treatment for diabetic foot, and to lay a foundation for the establishment of the core index set of the clinical trials on TCM treatment of diabetic foot. Computer retrieval of RCTs on TCM treatment of diabetic foot was performed in CNKI, Wanfang, SinoMed, PubMed, Cochrane Library, EMbase and Web of Science databases. Literature screening and data extraction were conducted independently by two researchers in strict accordance with inclusion and exclusion criteria. Any difference was resolved through discussion. A total of 72 RCTs involving 5 791 patients were included and 204 indicators were used. The number of indicators used in a single study was 2-22, with an average of 3 indicators used for each RCT. The indicators with top 16 frequency were clinical total effective rate, ankle brachial index(ABI), ulcer area, TCM syndrome integral, fibrinogen(FIB), fasting blood glucose(FBG), plasma viscosity(PV), c-reactive protein(CRP), saccharification blood of eggs(HbAlc), 2 h postprandial blood glucose(2 hPG), wound healing time, triglyce-rides(TC), TCM efficacy for syndromes, total cholesterol(TG), percutaneous oxygen partial pressure(TCPO2) and TCM symptom scores. The difference in selection of RCT indicators was large among TCM treatment methods for diabetic foot, and the combination of outcome indicators was arbitrary. The description on indexes was not standardized. Some non-laboratory examination indicators, some indicators not recommended in guidelines or not recognized in clinical practice, and some self-made indicators were not explained in detail. There was a lack of standardized evaluation criteria for indicators. The indicators had large time-point difference in measurement, and the time points were not distinguished in the measurement for diabetic foot patients with different degrees of severity. In addition, the patients with long course of treatment weren't timely measured. The characteristics of TCM or significant endpoint indicators were insufficient. It was urgent to establish the core index set of TCM in treating diabetic foot.
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Diabetes Mellitus , Pé Diabético , Medicamentos de Ervas Chinesas , Glicemia , Pé Diabético/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
The A-type Aurora kinase is upregulated in many human cancers, and it stabilizes MYC-family oncoproteins, which have long been considered an undruggable target. Here, we describe the design and synthesis of a series of pyrimidine-based derivatives able to inhibit Aurora A kinase activity and reduce levels of cMYC and MYCN. Through structure-based drug design of a small molecule that induces the DFG-out conformation of Aurora A kinase, lead compound 13 was identified, which potently (IC50 < 200 nM) inhibited the proliferation of high-MYC expressing small-cell lung cancer (SCLC) cell lines. Pharmacokinetic optimization of 13 by prodrug strategies resulted in orally bioavailable 25, which demonstrated an 8-fold higher oral AUC (F = 62.3%). Pharmacodynamic studies of 25 showed it to effectively reduce cMYC protein levels, leading to >80% tumor regression of NCI-H446 SCLC xenograft tumors in mice. These results support the potential of 25 for the treatment of MYC-amplified cancers including SCLC.
Assuntos
Aurora Quinase A/antagonistas & inibidores , Desenho de Fármacos , Inibidores de Proteínas Quinases/síntese química , Proteínas Proto-Oncogênicas c-myc/metabolismo , Pirimidinas/química , Animais , Aurora Quinase A/metabolismo , Aurora Quinase B/antagonistas & inibidores , Aurora Quinase B/metabolismo , Sítios de Ligação , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/metabolismo , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
To systemically evaluate the efficacy and safety of Gingko Ketone Ester Dropping Pills in treating angina pectoris and co-ronary heart disease. CNKI, Wanfang, SinoMed, PubMed, Cochrane Library and EMbase databases were retrieved on computer, and the randomized clinical trial(RCT) on Gingko Ketone Ester Dropping Pills in treating angina pectoris and coronary heart disease, which were published from the database establishment to December 31, 2019, were comprehensively collected. Literature screening, data extraction and quality evaluation were conducted independently by two researchers according to inclusion and exclusion criteria. Literature methodology quality evaluation was conducted with use of the Cochrane Handbook 5.3.0(bias risk assessment tool). Meta-analysis was performed with RevMan 5.3.0 software. A total of 10 RCTs were included. The results of the Meta-analysis showed that as compared with conventional Western medicine alone, the application of Gingko Ketone Ester Dropping Pills combined with conventional Western medicine treatment further improved the total effective rate and electrocardiogram effect(RR=1.43,95%CI[1.20,1.71],P<0.000 1). There were statistically significant differences in the number of angina attacks, the duration of angina and the amount of nitroglycerin used. In terms of safety indicators, four studies reported adverse reactions in the experimental group, including facial flu-shing, tachycardia, dizziness, dyspnea, nausea and other symptoms. Based on the existing findings, in the treatment of angina pectoris and coronary heart disease, Gingko Ketone Ester Dropping Pills combined with conventional Western medicine can improve the clinical total effective rate, electrocardiogram effect, number of angina attacks, duration of angina and the amount of nitroglycerin used. However, in the included studies, due to some methodological quality problems which would impact the reliability of literature results more high-quality randomized controlled trials are still needed for further verification.
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Doença das Coronárias , Medicamentos de Ervas Chinesas , Angina Pectoris/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Ésteres , Ginkgo biloba , Humanos , Cetonas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos TestesRESUMO
This study aimed to comprehensively analyze and compare the differences of different clinical study types currently published in the safety evaluation of Xuebijing Injection. Six databases, namely the Cochrane Library, PubMed, EMbase, CNKI, VIP and Wanfang database, were electronically retrieved to collect all types of studies on the safety of Xuebijing Injection, including randomized controlled trials, case-controlled studies, cohort studies, systematic reviews, and centralized monitoring studies of clinical safety(hospital), in order to comprehensively and objectively evaluate the safety of Xuebijing Injection, and analyze the differences of different research results. A total of 211 literatures were included, involving a total of 46 384 patients treated with Xuebijing Injection, and 423 adverse reactions(ADRs) occurred. They included 191 randomized controlled trials, 3 cohort studies, 15 systematic reviews, and 2 centralized monitoring studies of clinical safety(hospital), and the incidence of adverse reactions was 2.54%(common), 2.31%(common), 0.95%(occasionally), and 0.50%(occasionally). More than half of the 423 cases of ADRs occurred in skin and adnexal system(151 cases) and gastrointestinal system(65 cases), including such manifestations as rash, skin itching, nausea and vomiting, diarrhea. The degree of ADRs was mild. Randomized controlled trials showed that the incidence of ADR was the highest when Xuebijing Injection was used for malignant tumor and multiple organ failure. And the systematic evaluation showed that the incidence of ADR was the highest when Xuebijing Injection was used for spontaneous peritonitis of liver cirrhosis. In conclusion, different study types could lead to significant differences in the results of drug safety evaluation. Sample size, study type, and quality control are the main factors for biased results. Due to large sample size and high-quality, centralized monitoring studies become the better clinical safety evaluation model of drugs at present, and full life cycle management could more objectively reflect drug safety and guide clinical rational drug use.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos de Ervas Chinesas , Estudos de Casos e Controles , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , InjeçõesRESUMO
To evaluate the efficacy and safety of Compound Danshen Injection combined with Western medicine in the treatment of vascular dementia. Databases of Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP, Wanfang Data were electronically retrieved for collecting randomized controlled trial(RCT)about vascular dementia treated with Western medicine alone or combined with Compound Danshen Injection from the year of database establishment to January 2020. Two researchers independently screened out li-teratures, extracted data, and evaluated the risk of bias for inclusion in the study. Meta-analysis was conducted using RevMan 5.3 software. A total of 5 RCTs were included, involving 588 patients, with 299 in treatment group and 289 in control group. Meta-analysis results showed that compared with Western medicine alone, Compound Danshen Injection combined with Western medicine was better in the effective rate(RR=1.23,95%CI[1.14,1.33],P<0.000 01), MMSE score(MD=3.54,95%CI[3.01,4.06],P<0.000 01), ADL score(MD=11.49,95%CI[8.05,14.93],P<0.000 01), the level of CRP(MD=-0.72,95%CI[-1.25,-0.20],P=0.007) and the level of IL-6(MD=-7.64,95%CI[-9.65,-5.63],P<0.000 01). Adverse reactions mainly included rash and skin prick, which did not affect the treatment effect. Based on the findings, the combination of Compound Danshen Injection in the treatment of vascular dementia could improve the effective rates, relieve the mental state damage and improve the daily living ability, with mild adverse reactions and a low incidence. However, due to the low quality of the included literatures, high-quality and large-scale randomized controlled trials are needed for further verification.
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Demência Vascular , Medicamentos de Ervas Chinesas , Medicina , Salvia miltiorrhiza , Demência Vascular/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , InjeçõesRESUMO
The CXC chemokine receptor type 4 (CXCR4) receptor and its ligand, CXCL12, are overexpressed in various cancers and mediate tumor progression and hypoxia-mediated resistance to cancer therapy. While CXCR4 antagonists have potential anticancer effects when combined with conventional anticancer drugs, their poor potency against CXCL12/CXCR4 downstream signaling pathways and systemic toxicity had precluded clinical application. Herein, BPRCX807, known as a safe, selective, and potent CXCR4 antagonist, has been designed and experimentally realized. In in vitro and in vivo hepatocellular carcinoma mouse models it can significantly suppress primary tumor growth, prevent distant metastasis/cell migration, reduce angiogenesis, and normalize the immunosuppressive tumor microenvironment by reducing tumor-associated macrophages (TAMs) infiltration, reprogramming TAMs toward an immunostimulatory phenotype and promoting cytotoxic T cell infiltration into tumor. Although BPRCX807 treatment alone prolongs overall survival as effectively as both marketed sorafenib and anti-PD-1, it could synergize with either of them in combination therapy to further extend life expectancy and suppress distant metastasis more significantly.
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Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Receptores CXCR4/antagonistas & inibidores , Animais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Dietilnitrosamina/administração & dosagem , Dietilnitrosamina/toxicidade , Sinergismo Farmacológico , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/imunologia , Neoplasias Hepáticas Experimentais/patologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Ratos , Receptores CXCR4/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
To analyze the outcome indicators from the randomized controlled trials(RCTs) on traditional Chinese medicine(TCM) treatment for diabetic foot, and to lay a foundation for the establishment of the core index set of the clinical trials on TCM treatment of diabetic foot. Computer retrieval of RCTs on TCM treatment of diabetic foot was performed in CNKI, Wanfang, SinoMed, PubMed, Cochrane Library, EMbase and Web of Science databases. Literature screening and data extraction were conducted independently by two researchers in strict accordance with inclusion and exclusion criteria. Any difference was resolved through discussion. A total of 72 RCTs involving 5 791 patients were included and 204 indicators were used. The number of indicators used in a single study was 2-22, with an average of 3 indicators used for each RCT. The indicators with top 16 frequency were clinical total effective rate, ankle brachial index(ABI), ulcer area, TCM syndrome integral, fibrinogen(FIB), fasting blood glucose(FBG), plasma viscosity(PV), c-reactive protein(CRP), saccharification blood of eggs(HbAlc), 2 h postprandial blood glucose(2 hPG), wound healing time, triglyce-rides(TC), TCM efficacy for syndromes, total cholesterol(TG), percutaneous oxygen partial pressure(TCPO2) and TCM symptom scores. The difference in selection of RCT indicators was large among TCM treatment methods for diabetic foot, and the combination of outcome indicators was arbitrary. The description on indexes was not standardized. Some non-laboratory examination indicators, some indicators not recommended in guidelines or not recognized in clinical practice, and some self-made indicators were not explained in detail. There was a lack of standardized evaluation criteria for indicators. The indicators had large time-point difference in measurement, and the time points were not distinguished in the measurement for diabetic foot patients with different degrees of severity. In addition, the patients with long course of treatment weren't timely measured. The characteristics of TCM or significant endpoint indicators were insufficient. It was urgent to establish the core index set of TCM in treating diabetic foot.
Assuntos
Humanos , Glicemia , Diabetes Mellitus , Pé Diabético/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
This study aimed to comprehensively analyze and compare the differences of different clinical study types currently published in the safety evaluation of Xuebijing Injection. Six databases, namely the Cochrane Library, PubMed, EMbase, CNKI, VIP and Wanfang database, were electronically retrieved to collect all types of studies on the safety of Xuebijing Injection, including randomized controlled trials, case-controlled studies, cohort studies, systematic reviews, and centralized monitoring studies of clinical safety(hospital), in order to comprehensively and objectively evaluate the safety of Xuebijing Injection, and analyze the differences of different research results. A total of 211 literatures were included, involving a total of 46 384 patients treated with Xuebijing Injection, and 423 adverse reactions(ADRs) occurred. They included 191 randomized controlled trials, 3 cohort studies, 15 systematic reviews, and 2 centralized monitoring studies of clinical safety(hospital), and the incidence of adverse reactions was 2.54%(common), 2.31%(common), 0.95%(occasionally), and 0.50%(occasionally). More than half of the 423 cases of ADRs occurred in skin and adnexal system(151 cases) and gastrointestinal system(65 cases), including such manifestations as rash, skin itching, nausea and vomiting, diarrhea. The degree of ADRs was mild. Randomized controlled trials showed that the incidence of ADR was the highest when Xuebijing Injection was used for malignant tumor and multiple organ failure. And the systematic evaluation showed that the incidence of ADR was the highest when Xuebijing Injection was used for spontaneous peritonitis of liver cirrhosis. In conclusion, different study types could lead to significant differences in the results of drug safety evaluation. Sample size, study type, and quality control are the main factors for biased results. Due to large sample size and high-quality, centralized monitoring studies become the better clinical safety evaluation model of drugs at present, and full life cycle management could more objectively reflect drug safety and guide clinical rational drug use.
Assuntos
Humanos , Estudos de Casos e Controles , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Medicamentos de Ervas Chinesas/efeitos adversos , InjeçõesRESUMO
To evaluate the efficacy and safety of Compound Danshen Injection combined with Western medicine in the treatment of vascular dementia. Databases of Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP, Wanfang Data were electronically retrieved for collecting randomized controlled trial(RCT)about vascular dementia treated with Western medicine alone or combined with Compound Danshen Injection from the year of database establishment to January 2020. Two researchers independently screened out li-teratures, extracted data, and evaluated the risk of bias for inclusion in the study. Meta-analysis was conducted using RevMan 5.3 software. A total of 5 RCTs were included, involving 588 patients, with 299 in treatment group and 289 in control group. Meta-analysis results showed that compared with Western medicine alone, Compound Danshen Injection combined with Western medicine was better in the effective rate(RR=1.23,95%CI[1.14,1.33],P<0.000 01), MMSE score(MD=3.54,95%CI[3.01,4.06],P<0.000 01), ADL score(MD=11.49,95%CI[8.05,14.93],P<0.000 01), the level of CRP(MD=-0.72,95%CI[-1.25,-0.20],P=0.007) and the level of IL-6(MD=-7.64,95%CI[-9.65,-5.63],P<0.000 01). Adverse reactions mainly included rash and skin prick, which did not affect the treatment effect. Based on the findings, the combination of Compound Danshen Injection in the treatment of vascular dementia could improve the effective rates, relieve the mental state damage and improve the daily living ability, with mild adverse reactions and a low incidence. However, due to the low quality of the included literatures, high-quality and large-scale randomized controlled trials are needed for further verification.
Assuntos
Humanos , Demência Vascular/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Injeções , Medicina , Salvia miltiorrhizaRESUMO
To systemically evaluate the efficacy and safety of Gingko Ketone Ester Dropping Pills in treating angina pectoris and co-ronary heart disease. CNKI, Wanfang, SinoMed, PubMed, Cochrane Library and EMbase databases were retrieved on computer, and the randomized clinical trial(RCT) on Gingko Ketone Ester Dropping Pills in treating angina pectoris and coronary heart disease, which were published from the database establishment to December 31, 2019, were comprehensively collected. Literature screening, data extraction and quality evaluation were conducted independently by two researchers according to inclusion and exclusion criteria. Literature methodology quality evaluation was conducted with use of the Cochrane Handbook 5.3.0(bias risk assessment tool). Meta-analysis was performed with RevMan 5.3.0 software. A total of 10 RCTs were included. The results of the Meta-analysis showed that as compared with conventional Western medicine alone, the application of Gingko Ketone Ester Dropping Pills combined with conventional Western medicine treatment further improved the total effective rate and electrocardiogram effect(RR=1.43,95%CI[1.20,1.71],P<0.000 1). There were statistically significant differences in the number of angina attacks, the duration of angina and the amount of nitroglycerin used. In terms of safety indicators, four studies reported adverse reactions in the experimental group, including facial flu-shing, tachycardia, dizziness, dyspnea, nausea and other symptoms. Based on the existing findings, in the treatment of angina pectoris and coronary heart disease, Gingko Ketone Ester Dropping Pills combined with conventional Western medicine can improve the clinical total effective rate, electrocardiogram effect, number of angina attacks, duration of angina and the amount of nitroglycerin used. However, in the included studies, due to some methodological quality problems which would impact the reliability of literature results more high-quality randomized controlled trials are still needed for further verification.
Assuntos
Humanos , Angina Pectoris/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Ésteres , Ginkgo biloba , Cetonas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos TestesRESUMO
Mecicinal plants boast abundant natural compounds with significant pharmacological activity, and such compounds, featuring diversified and complex structures, can be used for research and development of drugs. At present, these natural compounds are directly extracted from herbs which, however, suffer from damaged wild resources and shortage of planting resources attributing to the increasing demand. Moreover, the low content in medicinal plants and complex structures are another challenge to the research and development of drugs. Heterologous synthesis with synthetic biology methods is a solution that has attracted wide attention. Synthetic bio-logy for the production of natural active compounds in Chinese medicinal plants involves the exploration of key enzymes in compound bio-synthetic pathways from plants, analysis of enzyme functions and mechanisms, and reconstruction and optimization of biosynthetic pathways in microorganisms for efficient synthesis of compounds. This study briefed the development process of synthetic biology and the biosynthetic pathways of terpenoids, alkaloids, and flavonoids, and summarized the related strategies of synthetic biology such as the reconstruction and optimization of metabolic pathways, regulation of fermentation process, and strain improvement, and the latest applications of heterogeneous synthetic biology in the production of natural compounds from Chinese medicinals. This study is expected to serve as a reference for the efficient production of terpenoids, alkaloids, flavonoids, and other active compounds from Chinese medicinal plants with strategies of synthetic biology.
Assuntos
Alcaloides , Vias Biossintéticas , China , Plantas Medicinais , Biologia SintéticaRESUMO
Folate status for women during early pregnancy has been investigated, but data for women during mid-pregnancy, late pregnancy or lactation are sparse or lacking. Between May and July 2014, we conducted a cross-sectional study in 1211 pregnant and lactating women from three representative regions in China. Approximately 135 women were enrolled in each stratum by physiological periods (mid-pregnancy, late pregnancy or lactation) and regions (south, central or north). Plasma folate concentrations were measured by microbiological assay. The adjusted medians of folate concentration decreased from 28·8 (interquartile range (IQR) 19·9, 38·2) nmol/l in mid-pregnancy to 18·6 (IQR 13·2, 26·4) nmol/l in late pregnancy, and to 17·0 (IQR 12·3, 22·5) nmol/l in lactation (Pfor trend < 0·001). Overall, lower folate concentrations were more likely to be observed in women residing in the northern region, with younger age, higher pre-pregnancy BMI, lower education or multiparity, and in lactating women who had undergone a Caesarean delivery or who were breastfeeding exclusively. In total, 380 (31·4 %) women had a suboptimal folate status (folate concentration <13·5 nmol/l). Women in late pregnancy and lactating, residing in the northern region, having multiparity and low education level had a higher risk of suboptimal folate status, while those with older age had a lower risk. In conclusion, maternal plasma folate concentrations decreased as pregnancy progressed, and were influenced by geographic region and maternal socio-demographic characteristics. Future studies are warranted to assess the necessity of folic acid supplementation during later pregnancy and lactation especially for women at a higher risk of folate depletion.
Assuntos
Ácido Fólico/sangue , Lactação , Estado Nutricional , Gravidez , Povo Asiático , Aleitamento Materno , China , Estudos Transversais , Feminino , Geografia , Humanos , Fatores de Risco , Fatores SociodemográficosRESUMO
To investigate the extensive application of Injection of Xuesaitong(lyophilized) in clinical real world study, and provide basis for clinical guidance on rational drug use and improvement of drug instructions. A prospective, multi-center, large-sample hospital centralized monitoring method was adopted to collect the general information and medication information of all patients who received Injection of Xuesaitong(lyophilized) during the study period in the respective monitoring units. Data analysis was performed using SAS 9.1 software. This study included 79 hospitals, with 30 097 patients being recruited. The patients who met the indications for stroke and hemiplegia accounted for 31.18%, those who experienced indications of chest pain and heartache accounted for 23.15%, and patients with central retinal vein occlusion indication accounted for 0.53%. The minimum single dose of Injection of Xuesaitong(lyophilized) was 20 mg, the maximum single dose was 1 000 mg, and the average single dose was(383.31±78.10) mg. 69.96% of the patients used 0.9% sodium chloride as the menstruum, 28.78% of the patients used 5% glucose as the menstruum, and 0.19% of the patients used 10% glucose as the menstruum. The minimum time for Injection of Xuesaitong(lyophilized) to dissolve is 0 min, 120 min maximally, and(14.26±13.73) min on an average basis. Patients using Injection of Xuesaitong(lyophilized) by intravenous drip accounted for 99.93%, with a slowest drip rate of 10 drops per min, fastest drip rate of 80 drops per min, and an average of(43.91±10.77) drops per min. Injection of Xuesaitong(lyophilized) was used for a minimum of 1 day and a maximum of 80 days, with an average of(8.22±5.12) days. Combined use with other injections accounted for 80.67%, 47.14% of them flushed the tube and 3.31% of them replaced infusion sets. The study found 40 cases of adverse reactions in patients with Injection of Xuesaitong(lyophilized), with an overall incidence of 0.13%(0.09% to 0.17%) for adverse reactions. In the real world application, the usage of Injection of Xuesaitong(lyophilized) basically meets the requirement of drug instructions in terms of indications, dosages, and methods of administration. However, it still needs to be improved in standardizing the selection of the menstruum, drip rate, course of treatment, and the combined usage of medicine.