ABSTRACT
Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.
ABSTRACT
Red blood cells, although their main function is currently considered to be oxygen delivery, are also closely related to immunity. There are increasing evidences that immature erythroid cells play important roles in diseases, especially in the development of tumors. This review mainly focused on the progress in the immunoregulation function of immature CD71 + erythroid cells and their roles under physiological and pathological states.
ABSTRACT
OBJECTIVE@#Agar dilution method (ADM) was used as the golden standard to evaluate the consistency of Epsilometer test (E-test) in detecting the sensitivity of Helicobacter pylori (H. pylori) to metronidazole.@*METHODS@#From August 2018 to July 2020, patients with H. pylori infection treated for the first time in Peking University Third Hospital for gastroscopy due to dyspepsia were included in this study. Gastric mucosas were taken from the patients with H. pylori infection. H. pylori culture was performed. Both the ADM and E-test were applied to the antibiotic susceptibility of H. pylori to metro-nidazole, and the consistency and correlation between the two methods were validated.@*RESULTS@#In the study, 105 clinical isolates of H. pylori were successfully cultured, and the minimum inhibitory concentration ≥ 8 mg/L was defined as drug resistance. Both ADM and the E-test showed high resistance rates to metronidazole, 64.8% and 62.9%, respectively. Among them, 66 drug-resistant strains were detected by ADM and E-test, and 37 were sensitive strains, so the consistency rate was 98.1%. Two strains were evaluated as drug resistance by ADM, but sensitive by the E-test, with a very major error rate of 1.9%. There was zero strain sensitive according to ADM but assessed as resistant by the E-test, so the major error rate was 0%. Taking ADM as the gold standard, the sensitivity of E-test in the detection of metronidazole susceptibility was 97.1% (95%CI: 0.888-0.995), and the specificity was 100% (95%CI: 0.883-1.000). Cohen's kappa analysis showed substantial agreement, and kappa coefficient was 0.959 (95%CI: 0.902-1.016, P < 0.001). Spearmans correlation analysis confirmed this correlation was significant (r=0.807, P < 0.001). The consistency evaluation of Bland-Altman method indicated that it was good, and there was no measured value outside the consistency interval. In this study, cost analysis, including materials and labor, showed a 32.2% higher cost per analyte for ADM as compared with the E-test (356.6 yuan vs. 269.8 yuan).@*CONCLUSION@#The susceptibility test of H. pylori to metronidazole by E-test presents better agreement with ADM. Because it is less expensive, less labor intensive, and more rapid, it is an easy and reliable method for H. pylori susceptibility testing.
Subject(s)
Humans , Metronidazole/therapeutic use , Helicobacter pylori , Agar/therapeutic use , Disk Diffusion Antimicrobial Tests , Microbial Sensitivity Tests , Helicobacter Infections/drug therapy , Anti-Bacterial Agents/therapeutic useABSTRACT
Objective To analyze the correlation between uric acid and coronary atherosclerotic heart disease in adults. Methods A total of 186 patients with hyperuricemia from January 2020 to October 2021 were selected as the observation group and 186 subjects with normal blood uric acid were selected as the control group . The levels of uric acid, hs-CRP, MCP-1, IL-6, RANTES and adropin protein were measured . The SYNTAX score was used to assess the risk of coronary heart disease and the incidence rate of coronary heart disease was recorded. The correlation between uric acid and inflammatory indexes was analyzed by linear regression model . The relationship between serum uric acid level and coronary atherosclerotic heart was tested by spearman correlation test. Results The levels of hs-CRP, MCP-1, IL-6, RANTES and adropin protein in the observation group were higher than the control group significantly (P<0.05) . The syntax score of the observation group was higher than the control group significantly (P<0.05) .The incidence rate of coronary heart disease in the observation group was significantly higher than that in the control group, and the difference was statistically significant (P<0.05). The level of uric acid was significantly positively correlated with hs-CRP, MCP-1, IL-6, RANTES and adropin . There was positive correlation between serum uric acid and syntax score and the incidence of coronary atherosclerotic heart disease (P<0.05). Conclusion The increase of uric acid level can predict coronary atherosclerotic heart disease. Patients with hyperuricemia should actively carry out uric acid lowering treatment to prevent the risk of coronary atherosclerotic heart disease.
ABSTRACT
Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and has serious implications for the health of mothers and their offspring. In recent years, studies have confirmed that air pollution is one of the main risk factors for diabetes, and there is increasing evidence that air pollution exposure is closely related to the occurrence of gestational diabetes. However, current studies on the association between air pollutant exposure and the incidence of gestational diabetes are inconsistent, and the window period of pollutant exposure is still unclear. Limited mechanistic studies suggest that airborne particulate matter and gaseous pollutants may affect GDM through multiple mechanisms, including inflammation, oxidative stress, disruption of adipokine secretion, and imbalance of intestinal flora. This review summarizes the relationship between air pollutant exposure and the incidence of GDM in recent years, as well as the possible molecular mechanism of the occurrence and development of GDM caused by air pollutants, in order to provide scientific basis for preventing pollutant exposure, reducing the risk of GDM, improving maternal and fetal outcomes and improving the quality of the birth population.
Subject(s)
Pregnancy , Female , Humans , Diabetes, Gestational/epidemiology , Air Pollution/analysis , Air Pollutants/analysis , Particulate Matter/analysis , Risk Factors , Maternal Exposure/adverse effectsABSTRACT
PURPOSE@#Child head injury under impact scenarios (e.g. falls, vehicle crashes, etc.) is an important topic in the field of injury biomechanics. The head of piglet was commonly used as the surrogate to investigate the biomechanical response and mechanisms of pediatric head injuries because of the similar cellular structures and material properties. However, up to date, piglet head models with accurate geometry and material properties, which have been validated by impact experiments, are seldom. We aim to develop such a model for future research.@*METHODS@#In this study, first, the detailed anatomical structures of the piglet head, including the skull, suture, brain, pia mater, dura mater, cerebrospinal fluid, scalp and soft tissue, were constructed based on CT scans. Then, a structured butterfly method was adopted to mesh the complex geometries of the piglet head to generate high-quality elements and each component was assigned corresponding constitutive material models. Finally, the guided drop tower tests were conducted and the force-time histories were ectracted to validate the piglet head finite element model.@*RESULTS@#Simulations were conducted on the developed finite element model under impact conditions and the simulation results were compared with the experimental data from the guided drop tower tests and the published literature. The average peak force and duration of the guide drop tower test were similar to that of the simulation, with an error below 10%. The inaccuracy was below 20%. The average peak force and duration reported in the literature were comparable to those of the simulation, with the exception of the duration for an impact energy of 11 J. The results showed that the model was capable to capture the response of the pig head.@*CONCLUSION@#This study can provide an effective tool for investigating child head injury mechanisms and protection strategies under impact loading conditions.
Subject(s)
Animals , Swine , Finite Element Analysis , Skull/injuries , Craniocerebral Trauma/diagnostic imaging , Brain , Biomechanical Phenomena , ScalpABSTRACT
To investigate the efficacy and value of optical genome mapping (OGM) in detecting chromosomal structural variations. In a clinical study about high-precision analysis of genomic structural variation for complex genetic diseases, a retrospective study was performed on the cases with karyotyping at the department of Obstetrics and Gynecology, and Endocrinology of Peking Union Medical College Hospital from January to December 2021. Ten cases with abnormal karyotype was detected by OGM. Partial cases were verified by fluorescence in situ hybridization (FISH), SNP array or CNV-seq. Results of ten cases, nine were detected with abnormality by OGM, including unbalanced chromosomal rearrangements (n=3), translocation (n=5) and paracentric inversion (n=1), and the results were in concordance with other standard assays. However, one case with breakpoint and reconnected at centromere has not been detected. In conclusion, ten samples were comprehensively analyzed by karyotyping, FISH, SNP array or CNV-seq, and OGM, and results demonstrated that optical genome mapping as a new technology can not only detect unbalanced rearrangements such as copy number variants as well as balanced translocations and inversions, but more importantly, it can refine breakpoints and orientation of duplicated segments or insertions. So it can contribute to the diagnosis of genetic diseases and prevent birth defect. However, the current technology is not yet capable of detecting breakpoints of balanced structural variations lying within unmapped regions.
Subject(s)
Female , Humans , Pregnancy , Chromosome Mapping , In Situ Hybridization, Fluorescence , Karyotyping , Retrospective Studies , Translocation, GeneticABSTRACT
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective cure for many hematologic and non-hematologic diseases.However, infection morbidity and mortality remain high after allo-HSCT, which is closely related to the recovery of immune cell subsets.The detailed information on the recovery of natural killer(NK), T and B cell subsets can better predict and regulate the occurrence of adverse events.This article will review the current rules, influencing factors and the relationship between the outcome and the immune reconstitution of NK cells, T cells and B cells after hematopoietic stem cell transplantation.
ABSTRACT
Objective: To summarize the clinical characteristics of patients with Takotsubo syndrome (TTS) from China and compare these features with patients from Europe/North America. Methods: We reviewed case reports published between 1990 and 2020 with the key words of "Takotsubo syndrome" "stress cardiomyopathy" "apical balloon syndrome" and "broken heart syndrome", in Wanfang, CNKI, Pubmed and Web of Science databases, and 1 294 articles were identified, including 128 articles reporting 163 cases in China and 1 166 articles reporting 1 256 cases in Europe/North America. The characteristics of demographics, triggers, symptoms, electrocardiogram, echocardiography, left ventriculogram,coronary angiography, treatment and prognosis were analyzed and compared between Chinese and European/North American cases. Results: A total of 1 294 articles (1 419 cases: 163 from China, 1 256 from Europe/North America) were included in the final analysis. The characteristics of Chinese cases included: (1) demographic:the age was (59.6±16.9) years, which was similar with that of European/North American ((59.7±17.4) years, P=0.90), and female accounting for 78.5% (128/163), which was lower than that of European/North American (85.4% (1 073/1 256), P=0.02). (2) Triggers:mental triggers accounted for 48.5% (79/163), physical triggers accounted for 43.6% (71/163), and no triggers accounted for 7.9% (13/163), respectively. Compared with Europe/North America, the ratio of patients with mental triggers was higher in China, while the ratio of patients with physical triggers and no triggers was lower (P<0.05). (3) Symptoms: chest pain (52.8% (86/163)), chest tightness (35.0% (57/163)), shortness of breath (33.1% (54/163)), dizziness (16.0% (26/163)), sweating (15.3% (25/163)), palpitations (12.3% (20/163)), syncope (9.2% (15/163)) abdominal pain/diarrhea (8.6% (14/163)), hypotension (7.4% (12/163)), and fatigue (1.2% (2/163)) were illustrated in sequence. Compared with patients in Europe/North America, the ratio of patients with chest tightness, dizziness, sweating, palpitations, abdominal pain/diarrhea was higher in Chinese patients, while the ratio of patients with hypotension was lower in Chinese patients (P<0.05). (4) Electrocardiogram: main manifestations were myocardial ischemia symptoms, such as ST-segment elevation (63.8% (104/163)), T wave inversion (46.0% (75/163)), ST-segment depression (8.6% (14/163)). Compared with European/North American, the ratio of patients with ST-segment elevation, T wave inversion, and atrioventricular block was higher in Chinese patients (P<0.05). (5) Echocardiography and imaging:apical dyskinesia (59.5% (97/163)) and apical/left ventricular bulbar dilation (36.2%(59/163)) dominated the echocardiography findings. Compared with European/North American, the ratio of patients with apical dyskinesia, apical/left ventricular bulbar dilation, and mitral regurgitation was higher in Chinese patients, while the ratio of patients with dyskinesia in other parts and left ventricular ejection fraction<50% was lower in Chinese patients (P<0.05). Left ventricular angiography showed 36.2% (59/163) of apical dyskinesia in Chinese patients, which was higher than that reported in European/North American patients, and 38.7% (63/163) of apical/left ventricular bulbar dilation was reported in Chinese patients, which was similar to that reported in European/North American patients. Coronary angiography showed percent of no stenosis or stenosis less than 50% was 87.1% (142/163), which was similar to that reported in European/North American patients (P>0.05). The typical type of TTS accounted for 96.3% (157/163), which was significantly higher than that reported in European/ American patients, while the ratio of basal type and midventricular type was lower (P<0.01). (6) Treatment and prognosis:the applied drugs in China were listed in order as following, β-blockers (41.1% (67/163)), antiplatelet agents (37.4%(61/163)), ACEI/ARB (36.2%(59/163)), anticoagulants (27.0%(44/163)), diuretics (19.6% (32/163)), etc. Compared with Europe/North America, the ratio of antiplatelet agents, anticoagulants, statins, diuretics, and nitrates use was higher in China (P<0.05), while the use of oxygen therapy and IABP was similar (P>0.05). The hospital mortality in China was 5.5% (9/163), during 1-year follow-up the recurrence rate was 3.7% (6/163) and the mortality was 0. The prognosis was similar with that in Europe/North America. Conclusions: Compared with TTS cases in Europe/North America, TTS cases in China also occur usually in middle-aged and elderly women, most of whom have mental/physical triggers and typical imaging manifestations, followed by a low hospital mortality rate and recurrence rate.
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Abdominal Pain/complications , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Anticoagulants , Arrhythmias, Cardiac/complications , China/epidemiology , Diuretics , Dizziness/complications , Dyskinesias/complications , Electrocardiography , Europe/epidemiology , Hypotension/complications , Platelet Aggregation Inhibitors , Stroke Volume , Takotsubo Cardiomyopathy/etiology , Ventricular Function, LeftABSTRACT
ObjectiveTo explore the mechanism of Liu Junzitang in preventing and treating muscle atrophy in mice with lung cancer cachexia based on the signal transducer and activator of transcription 3(STAT3)/ubiquitin proteasome pathway in vivo. MethodForty C57BL/6 mice aged six weeks were randomly divided into a blank group, a model group, a Liu Junzitang group, an inhibitor group (stattic group),and a Liu Junzitang + inhibitor group (combination group), with eight mice in each group. The cachectic muscle atrophy model was induced by subcutaneous inoculation of Lewis lung cancer cell line under the right anterior armpit in mice except those in the blank group. On the 8th day after subcutaneous inoculation, the mice in the corresponding groups received Liu Junzitang (9.56 g·kg-1·d-1) by gavage and intraperitoneal injection of stattic [25 mg·kg-1·(2 d)-1]. After three weeks of drug intervention, the body weight and gastrocnemius muscle weight were recorded. Hematoxylin-eosin (HE) staining was used to observe the pathological changes and cross-sectional area of gastrocnemius muscle fibers in mice. Western blot was used to detect the expression of phosphorylated-STAT3 (p-STAT3), STAT3, muscle atrophy F-box (MAFbx), and muscle RING finger protein 1 (MuRF1) in the gastrocnemius muscle. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of STAT3, MAFbx, and MuRF1 in the gastrocnemius muscle. ResultCompared with the blank group, the model group showed lightened body and the gastrocnemius muscle, reduced cross-sectional area of gastrocnemius muscle fibers, and increased protein expression of p-STAT3, STAT3, MAFbx, and MuRF1 and mRNA expression of STAT3, MuRF1, and MAFbx in the gastrocnemius muscle (P<0.05). Compared with the model group, the Liu Junzitang group showed increased body weight, gastrocnemius muscle weight, and cross-sectional area of gastrocnemius muscle fibers (P<0.05), and decreased protein expression of p-STAT3, STAT3, MuRF1, MAFbx, and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle (P<0.05). Compared with the model group, the inhibitor group showed increased body weight and cross-sectional area of gastrocnemius muscle fibers (P<0.05), and reduced protein expression of p-STAT3, STAT3, MuRF1, MAFbx, and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle (P<0.05). Compared with the model group, the combination group showed increased body weight and gastrocnemius muscle weight (P<0.05),and decreased protein expression of p-STAT3, STAT3, MuRF1, and mRNA expression of STAT3 and MAFbx in the gastrocnemius muscle (P<0.05). Compared with the Liu Junzitang group, the stattic group and the combination group showed reduced expression of p-STAT3 protein in the gastrocnemius muscle (P<0.05). ConclusionLiu Junzitang can prevent and treat muscle atrophy in mice with lung cancer cachexia, and its mechanism may be associated with the protein and mRNA expression related to the STAT3-mediated ubiquitin proteasome pathway.
ABSTRACT
Aim To investigate the effect of extracellular vesicles secreted by adipose tissue of mice on hippocampal neurons and cognitive behavior of mice with a high-fat diet.Methods Twenty C57BL/6J male mice were randomly divided into normal diet(ND)group(n=10)and high-fat diet(HFD)group(n=10), fed for 28 weeks.The weight of mice was recorded weekly.The level of fasting blood glucose, insulin and the insulin resistance index(HOMA-IR)of mice were tested at week 27.At week 28, the learning and memory abilities of mice were assessed by the Morris water maze.The morphological differences in adipose tissue were observed by HE staining, and the extracellular vesicles secreted from adipose tissue were quantified by TEM and NTA.Extracellular vesicles derived from adipose tissue labeled with PKH 67 were injected into normal mice via the tail vein, and after 30 h, the uptake of extracellular vesicles was detected in the hippocampal slice.The primary hippocampal neurons were treated with extracellular vesicles with the same amount of protein, and the effects of them on neuronal morphology and cell viability were observed.Results Compared with ND group, mice in HFD group were significantly heavier, with hyperglycemia, hyperinsulinemia and higher insulin resistance index.In the Morris water maze test, the HFD group showed a longer escape latency and less swimming time in the target zone.The volume of adipocytes and the amount of extracellular vesicles secreted from them significantly increased in HFD group.Extracellular vesicles secreted by adipose tissue could be internalized by both the primary hippocampal neurons and the hippocampal neurons in the normal mice.Compared with ND group, extracellular vesicles secreted by adipose tissue of the HFD group significantly reduced the length of primary hippocampal neuronal dendrites, the number of primary and secondary dendrites, and the cell viability of neuron cells.Conclusion Long-term high-fat diet could damage the hippocampal neurons by affecting the extracellular vesicles derived from adipose tissue.
ABSTRACT
Objective:The incidence rate of cancer cachexia is high in late stage of cancer, which is characterized by skeletal muscle atrophy and rapid reduction of adipose tissue and systemic inflammation. Cachexia is highly related to a variety of tumors, and causes a large proportion of cancer deaths. Cancer cachexia can lead to serious complications in patients with cancer, then, the quality of life of patients decreases, the psychological state becomes negative, and the state of illness is further worsened. At present, there is no effective intervention means to completely reverse cachexia. The combined use of multiple targets and effective components of traditional Chinese medicine(TCM), as well as the treatment based on syndrome differentiation and the theory of TCM play an important role in the prevention and treatment of cancer cachexia. Therefore, exploring the pathogenesis of cancer cachexia and prevention and treatment with TCM is helpful for basic study and clinical application. Method:In this paper, cancer cachexia and TCM in China national knowledge infrastructure (CNKI) and Public Medline (PubMed) databases were retrieved, and 98 Chinese and English literatures were included through summarization to elaborate the pathogenesis of cancer cachexia and the prevention and treatment of TCM. Result:Emphasis was given to the important role of inflammatory reaction, skeletal muscle atrophy, energy metabolism abnormality and multiple signal joint regulation in occurrence of cancer cachexia, and the unique advantages and significant role of TCM in treatment of cancer cachexia under different treatment principles. Conclusion:Inflammatory reaction, skeletal muscle atrophy, abnormal energy metabolism make the pathogenesis of cancer cachexia complex and diverse. TCM prescriptions, Chinese herbal medicine and their effective ingredients have the natural advantages of targeting multiple pathways, controlling multiple signal pathways and inhibiting various inflammatory factors in the prevention and treatment of cancer cachexia, and are safe and effective in improving diet, prolonging the survival period of patients and keeping weight.
ABSTRACT
With the emerging cases of tumor is about to exceed 4 million per year in China, tumor prevention and control is also a formidable barrier hitting the world. Overall, an increasing trend of incidence and mortality of tumor in China has been observed in recent years, and the high mortality and low cure rate of tumor have seriously threaten the health of Chinese people, greatly affected the quality of life of patients, greatly reduced the living standard of patients and endangered the physical and mental health of patients. Traditional Chinese medicine(TCM) believes that the etiology of tumor is complex and pathogenesis is variable, which is the result of interaction between internal and external factors. If the treatment is carried out based on syndrome differentiation in time at the beginning when exogenous pathogens act on the human body, so as to prevent the spread of latent pathogen in human body, the occurrence and development of tumor diseases will be significantly reduced. Therefore, the theory of exogenous pathogenic factors and the pathogenesis of tumor need to be further explored. A total of 67 Chinese and English literatures were searched out with key words like external contraction, pathogenic Qi, TCM, tumor and pathogenesis in China National Knowledge Infrastructure (CNKI) and Public Medline (PubMed) databases for reference, so as to discuss the theory of exogenous pathogens and the pathogenesis of tumor comprehensively. The important role of exogenous pathogens in tumor pathogenesis and the significance of TCM in the early prevention and treatment of tumors were emphasized. Exogenous pathogenic factors such as wind, cold, dampness, fire, natural and social factors, diet and living conditions lead to the complexity of the occurrence of tumors. TCM can effectively prevent and intervene in the early stage of tumor onset, contribute to disease prevention and tumor resistance, reduce the occurrence, development and transformation of tumors, and make the clinical medication more effective, more accurate and more targeted, so as not to miss the opportunity for treating tumor, and provide a more clear guidance for clinical treatment of tumors.
ABSTRACT
Depression is a mental illness characterized by persistent negative feelings, which has seriously threatened people's health. In recent years, neuronal autophagy, an important stress response, has also been regarded as a hypothesis for the pathogenesis of depression. Relevant studies have shown that either insufficient or excessive autophagy triggers neuronal damage, and activated or inhibited neuronal autophagy can be observed in animal models of depression. Therefore, neuronal autophagy may be a double-edged sword involved in the pathogenesis of depression. It is believed in traditional Chinese medicine (TCM) that the occurrence of this disease is closely related to liver depression and spleen deficiency. Chinese medicine regulates the neuronal autophagy via multiple ways. The TCM monomers that regulate neuron autophagy are capable of protecting nerves or penetrating the blood-brain barrier. TCM compounds designed for soothing liver or invigorating spleen have been proved effective against this disease, demonstrating that the core pathogenesis of depression lies in liver depression and spleen deficiency. The regulatory effects of TCM on neuronal autophagy in depression models might result from its action on multiple targets, multiple pathways, and multiple systems. This paper discussed the limitations in current research based on the involvement of neuronal autophagy in depression and its treatments, in order to provide ideas for later similar research and that concerning TCM treatment of depression.
ABSTRACT
Objective:To investigate the relationship between preoperative serum thyroglobulin (Tg) and clinical data with the risk of cervical lymph node metastasis in patients with papillary thyroid carcinoma (PTC) .Methods:Data of 395 PTC patients who underwent surgery from Feb. 2016 to Jun. 2019 at the Second Affiliated Hospital of Soochow University were retrospectively analyzed. Based on whether cervical lymph nodes had metastasis, patients were classified into central lymph node metastasis positive group ( n=195 cases) , central lymph node metastasis negative group ( n=200 cases) , lateral lymph node metastasis positive group ( n=72 cases) , and lateral lymph node metastasis negative group ( n=323 cases) .Then the relationship between age, sex, multifocality, tumor diameter, capsular invasion, preoperative TSH and preoperative Tg with lymph node metastasis were analyzed by SPSS. Comparisons between groups were performed by χ2 test and rank sum test. Prediction efficiency of the preoperative Tg and Logistic regression model was estimated by receiver operating characteristic (ROC) curve. A total of 100 PTC patients confirmed by pathological results in the Second Affiliated Hospital of Soochow University from Jul. 2019 to Apr. 2020 were selected as the validation data. Results:Multi-factor Logistic regression showed that age, tumor diameter, capsular invasion and preoperative Tg were independent risk factors of central cervical lymphatic metastasis ( P<0.05) ; Tumor diameter, capsular invasion, central cervical lymphatic metastasis and preoperative Tg were independent risk factors of lateral cervical lymphatic metastasis ( P<0.05) . The area under the ROC curve (AUC) for diagnosing central lymph node metastasis by preoperative Tg was 0.710, with a sensitivity of 49.2%, and specificity of 88.5%. The AUC for diagnosing lateral lymph node metastasis by preoperative Tg was 0.728, with a sensitivity of 59.7%, and specificity of 89.5%. The AUC for diagnosing central lymph node metastasis by the prediction model was 0.773, with a sensitivity of 78.5%, and specificity of 64.5%.The AUC for diagnosing lateral lymph node metastasis by the prediction model was 0.869, with a sensitivity of 84.7%, and specificity of 70.3%. Conclusions:The preoperative serum Tg level is correlated with cervical lymph node metastasis in PTC patients. But the Logistic regression model based on preoperative Tg and other independent risk factors shows a better predictive value.
ABSTRACT
Objective: To observe the clinical efficacy of Tuina (Chinese therapeutic massage) manipulation for pediatric adenoid hypertrophy (AH). Methods: A total of 60 children with AH were randomized into an observation group and a medication group, with 30 cases in each group. The observation group was treated with pediatric Tuina treatment, and the medication group was treated with 0.05% mometasone furoate nasal spray. The changes of main clinical symptom score, quality of life (QOL) score and X-ray nasopharynx lateral film were observed, and the clinical efficacy was evaluated. Results: The total effective rate of the observation group was 90.0%, and that of the medication group was 66.7%. The difference between the two groups was statistically significant (P<0.05). After treatment, the A/N value [ratio of adenoid thickness (A) and nasopharyngeal cavity width (N)] of posterior nasopharyngeal lateral film did not show significant change in either group (P>0.05). After treatment, the clinical symptom scores in both groups decreased, and the intra-group differences were statistically significant (P<0.001), but there was no statistical difference between the two groups (P>0.05). After treatment, the QOL scores of children in both groups decreased, and the intra-group differences were statistically significant (P<0.001), and the difference between the two groups was statistically significant (P<0.001). Conclusion: Tuina manipulation is effective in treating pediatric AH, and produces a better effect in improving traditional Chinese medicine symptoms and QOL than 0.05% mometasone furoate nasal spray.
ABSTRACT
OBJECTIVE@#To observe the effect of acupuncture for regulating spleen and stomach on aspirin resistance in patients with type 2 diabetes mellitus (T2DM) and explore the effect mechanism.@*METHODS@#A total of 68 T2DM patients complicated with aspirin resistance were randomized into an observation group and a control group, 34 cases in each one. On the base of the conventional treatment for diabetes, aspirin enteric-coated tablets were prescribed for oral administration, 100 mg each time, once daily in the control group. In the observation group, on the basis of the treatment as the control group, acupuncture was used for regulating spleen and stomach at Zhongwan (CV 12), Zusanli (ST 36), Yinlingquan (SP 9), Hegu (LI 4), etc., once daily. The treatment for 1 week was as one course and 4 courses of treatment were required totally in two groups. Before and After treatment, the indexes of platelet function (platelet aggregation rate [PAG] and salicylic acid concentration), the indexes of vascular endothelial function (6-keone prostaglandin F1α[6-keto-PGF1α], thromin B2 [TXB2] and cyclooxysynthase-2 [COX-2]), blood glucose (fasting plasma glucose [FPG], 2 h plasma glucose [2h PG] and glycosylated hemoglobin [HbA1c]), insulin resistance index (HOMA-IR), blood lipid indexes (total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) and the total score of TCM symptoms were observed in the patients of two groups. Clinical therapeutic effect and safety was compared in the patients between the two groups after treatment and the recurrence rate of cardiocerebrovascular events was followed up 6 months after treatment.@*RESULTS@#After treatment, PAG, salicylic acid concentration, TXB2, COX-2, FPG, 2h PG, HbA1c, HOMA-IR, LDL-C, TC, TG and the total scores of TCM symptoms were all reduced as compared with those before treatment in the two groups (@*CONCLUSION@#Acupuncture for regulating spleen and stomach combined with aspirin enteric-coated tablets relieve insulin resistance and reduces blood glucose and lipid as well as the recurrence rate of cardiocerebrovascular events in the patients with T2DM, which is probably related to the regulation of insulin resistance and the improvement of vascular endothelial function. This combined therapy achieves the better effect on aspirin resistance as compared with simple aspirin enteric-coated tablets.
Subject(s)
Humans , Acupuncture Points , Acupuncture Therapy , Aspirin , Diabetes Mellitus, Type 2/drug therapy , Spleen , StomachABSTRACT
OBJECTIVE: To analyze the effects and the underlying mechanisms of photoperiodism and exposure to bisphenol A(BPA) on hepatic lipid metabolism in female mice. METHODS: A 2×2 factorial design was used. The photoperiod factor was set to fixed and shifted photoperiod, and the BPA factor was set to BPA exposure(BPA group) and non-exposure(control group). Specific pathogen free female C57 BL/6 J mice were randomly divided into four groups: fixed photoperiod control group, shifted photoperiod control group, fixed photoperiod BPA group, and shifted photoperiod BPA group, with eight rats in each group. The fixed photoperiod mice received a 12 ∶12 hours light-dark cycle, and the shifted photoperiod mice experienced reversed light-dark cycle once a week. Mice in BPA group were administered a dose of BPA 50 μg/kg body weigh by gavage, while mice in control group were given a equal volume of corn oil, once per day, five days per week for 12 weeks. The body weight of mice was measured during the experiment. After 12 weeks, all mice in each group were sacrificed. Plasma was collected and the levels of biochemical parameters were measured. Liver tissues were separated for examination of lipid deposition using oil red O and hematoxylin-eosin staining, and plasma triglyceride levels were measured. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA relative expression of genes of fat metabolism in liver tissues. RESULTS: At the end of the experiment, the body weights of mice were higher than that before the experiment(all P<0.05), but there was no statistically significant difference in body weights among the four groups(all P>0.05). The levels of plasma glucose, triglyceride and activity of alanine aminotransferase were higher in shifted photoperiod mice than that in the fixed photoperiod mice(all P<0.05). The plasma aspartate transaminase level was higher in BAP group than that in control group(P<0.01). The area of lipid staining in hepatic tissue was larger in the shifted photoperiod control group, fixed photoperiod BPA group and shifted photoperiod BPA group(all P<0.05), and hepatic lipid droplets aggregation was increased in these three groups compared with the fixed photoperiod control group. The mRNA relative expression of acetyl-coenzyme A carboxylase alpha(Acaca) was higher in the fixed photoperiod BPA and shifted photoperiod control groups(all P<0.05), compared with the fixed photoperiod control group. The relative expression of Acaca mRNA was lower in the shifted photoperiod BPA group than that in the fixed photoperiod BPA group(P<0.05). The mRNA relative expression of sterol regulatory element binding protein(Srebp) 1 and Srebp2 were significantly higher in the BPA group than that in the control group(all P<0.05). CONCLUSION: Both the single shifted photoperiod or BPA exposure can increase hepatic lipid deposition in female mice. The mechanism may be related to up-regulation of the mRNA expression of Acaca, Srebp1 and Srebp2. The shifted photoperiod in combination of BPA exposure has an antagonistic effect on the expression of Acaca mRNA in liver tissues of female mice.
ABSTRACT
Protein arginine methyltransferase 5 (PRMT5) is an important type II human methyltransferase. It catalyzes the symmetrical double-methylation of many histones and non-histones, and it is highly expressed in many kinds of tumors. PRMT5 has been proven to be a potential new target for cancer treatment. Based on the reported crystal complex of EPZ015666 with PRMT5, a series of new compounds was designed using GSK3326595 (EPZ015938) as the lead compound and using the conformational restriction approach. We found that compounds B8 and the C series of derivatives displayed enzyme inhibitory activity comparable to that of GSK3326595. Compounds C3 and C4 showed poor permeability in Caco-2 cells, and that might be one of the reasons for their poor anti-proliferative activity against Z-138 cells. These data provide insights for further structural optimization.
ABSTRACT
OBJECTIVE@#To observe the clinical effects of zheng's massage combined with electroacupuncture in the treatment ofreflex sensory dystrophy syndrome of the wrist.@*METHODS@#From October 2016 to September 2018, 48 cases of reflex sensory dystrophy syndrome of the wrist were divided into the observation group and the control group. In the observation group, there were 24 cases, including 10 males and 14 females, ranging in age from 54 to 76 years old, with an average age of (61.41 ±7.90) years old. The patients in the observation group were treated with massage combined with electroacupuncture. The control group consisted of 24 patients, including 9 males and 15 females, ranging in age from 52 to 75 years old, with an averageage of (58.71±8.11 ) years old. The patients in the control group were treated with electroacupuncture alone. All the patients in both groups were treated for 6 weeks. The clinical symptoms and signs, visual anglogue scale (VAS), Cooney wrist score and clinical efficacy evaluation were compared between the two groups before and after treatment, and statistical analysis was conducted.@*RESULTS@#After 6 weeks of treatment, VAS in the control group was 4.9±1.8, and Cooney wrist score was 74.63±1.72; VAS in the observation group was 2.2±1.4, and Cooney wrist score was 86.31±2.53. The comprehensive scores of VAS and Cooney wrist joint between two groups were improved after treatment, and the observation group was better than control group(<0.05). The curative effect of the observation group was better than that of the control group.@*CONCLUSION@#Zheng's massage combined with electroacupuncture has the following advantages in the treatment of reflex sympathetic dystrophy syndrome of the wrist, such as small trauma, patients' willingness promoting functional rehabilitation, which is worthy of clinical promotion.