This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Objective: To examine the effect of dietary behaviors on handgrip strength loss among the elderly, so as to provide insights into the prevention of handgrip strength loss. Methods : Based on the health surveillance cohort among the elderly in Zhejiang Province, two villages or communities were randomly sampled from each of Shaoxing and Zhoushan cities using a multi-stage cluster sampling method, and all residents that had lived in local areas for one year and longer and had an age of 60 years and older were enrolled. Participants' demographics, dietary behaviors, smoking, drinking, and exercise were collected through questionnaire surveys, and the height, body weight and handgrip strength were measured. The handgrip strength loss was diagnosed according the 2019 Consensus Update on Sarcopenia Diagnosis and Treatment proposed by Asian Working Group for Sarcopenia, and the effect of dietary behaviors on handgrip strength loss was examined using a multivariable logistic regression model. Results: A total of 1 265 residents were enrolled, with a mean age of (70.67±7.30) years, and including 565 men (44.66%) and 700 women (55.34%). The overall prevalence of handgrip strength loss was 42.85% among the participants, and the prevalence was 40.35% in men and 44.86% in women, respectively. Multivariable logistic regression analysis showed that nut intake for 1 to 3 times a week (OR=0.180, 95%CI: 0.088-0.367) and for 4 to 6 times a week (OR=0.241, 95%CI: 0.113-0.514) led to a reduced risk of handgrip strength loss among the elderly, and intake of sugary drinks for 4 to 6 times a week led to an increased risk of handgrip strength loss among the elderly (OR=2.298, 95%CI: 1.120-4.714) after adjustment for age, body mass index, educational level and exercise. Conclusion Intake of nuts and sugary drinks may affect the development of handgrip strength loss among the elderly.

Objective:To establish a high performance liquid chromatography （HPLC） fingerprint of branches of Juglans mandshurica and to evaluate the quality of the samples from different producing areas and in different harvest periods. Method:Chromatographic separation was performed on an Agilent Poroshell 120 SB-C₁₈ column （2.1 mm×100 mm， 2.7 μm） for gradient elution with mobile phase of 0.2% formic acid solution （A）-0.2% formic acid acetonitrile solution （B） （0-5 min， 5%-10%B； 5-25 min， 10%-16%B； 25-40 min， 16%-22%B； 40-45 min， 22%-45%B； 45-50 min， 45%-65%B； 50-52 min， 65%-100%B； 52-55 min， 100%B） at a flow rate of 0.3 mL·min^-1. The column temperature was 30 ℃ and the detection wavelength was 270 nm. The quality of branches of Juylans mandshurica was evaluated by similarity evaluation， cluster analysis， principal component analysis and partial least squares-discriminant analysis. The chemical constituents of the samples were identified by HPLC coupled with quadrupole time-of-flight mass spectrometry （HPLC-Q-TOF-MS/MS）. The mass spectrometry was conducted in negative ion mode with electrospray ionization（ESI）. Data were acquired over a range of m/z 100-1 700 for MS and m/z 50-1 700 for MS/MS. Result:A total of 19 common peaks were confirmed in 40 batches of samples， and the similarity ranged from 0.430 to 0.995， of which the similarity of samples collected in spring and winter seasons （April， May and December） was greater than 0.90， while the similarity of most samples collected in summer （July to September） was low. Multivariate statistical analysis showed that the samples were divided into two groups according to the harvest time， but there was no obvious classification rule for the samples from different producing areas. The contents of most constituents in the samples collected in spring and winter were higher than those collected in summer. The result illustrated that different harvest periods had great influence on the quality of branches of J. mandshurica. Compared with the samples collected in summer， the quality of samples collected in spring and winter was better. A total of 22 peaks were proved to be the main constituents that contributed to the difference between samples collected in different seasons. A total of 83 chemical components were identified by HPLC-Q-TOF-MS/MS， including 49 tannins， 7 organic acids， 14 naphthalene derivatives， 1 flavonoid， 6 anthracene derivatives， 2 lignans， 3 diarylheptanoids and 1 saccharide. Totally 13 common peaks were identified. Of the peaks that contributed to discriminate samples collected in different season， 19 peaks were identified and most of them were tannins. Conclusion:The established HPLC fingerprint can provide useful information for the quality evaluation of branches of J. mandshurica. Tannin is the main constituents in the samples. Harvest period has great influence on the quality of branches of J. mandshurica.

Objective To observe the metabolomics changes of serum after skin incision of rats and to determine the wound age of skin incision. Methods A rat skin incision model was established, 21 SD rats were divided into 1 h, 2 h, 4 h, 8 h, 16 h, 24 h after skin incision groups and the control group, then blood was taken from rats in the experimental groups at the corresponding time points after injury, and taken from the control group directly. Gas chromatography-mass spectrometry （GC-MS） technology was used to detect serum metabolites and screen marker metabolites, then orthogonal partial least square-discriminant analysis （OPLS-DA） model was used to establish a regression model for the relationship between marker metabolite content and wound age to determine wound age of skin. Results GC-MS was used to detect the serum collected, and 21 marker metabolites were obtained through initial screening, and 4 marker metabolites were further analyzed and screened using multivariate statistical analysis methods. There was no correspondence between the change rule of the serum content and wound age, therefore it cannot be used directly to determine wound age. OPLS model could be used to obtain regression models of the content and wound age of 21 marker metabolites and 4 marker metabolites, both of which can determine wound age, but the prediction accuracy of the regression model of 21 marker metabolites was significantly higher. Conclusion Using metabolomics to establish a regression model of the metabolite content and wound age has the potential to be applied to skin incision wound age determination.
Animals ; Biomarkers ; Gas Chromatography-Mass Spectrometry ; Metabolomics ; Rats ; Rats, Sprague-Dawley ; Skin

Objective: To investigate the predictive value of N-terminal type B natriuretic peptide（NT-proBNP) on the prognosis of elderly hospitalized patients without heart failure（non-heart failure). Method: Elderly patients aged 65 years or older, who were admitted to Beijing Hospital from September 2018 to February 2019, were enrolled in this study. Patients with clinical diagnosis of heart failure or left ventricular ejection fraction（LVEF)<50% were excluded. The patients were divided into 2 groups based on the serum NT-proBNP level: low NT-proBNP group （<125 ng/L) and high NT-proBNP group（≥125 ng/L). Patients were followed up at 3, 6, and 12 months after enrollment, and the major adverse events were recorded. The composite endpoint events included all-cause mortality, readmission or Emergency Department visits. Cardiovascular events include death, readmission or emergency room treatment due to cardiogenic shock, myocardial infarction, angina pectoris, arrhythmia, heart failure or stroke/transient ischemic attack. Results: A total of 600 elderly patients with non-heart failure were included in the analysis. The average age was （74.9±6.5) years, including 304（50.7%) males. The median follow-up time was 344（265, 359) days. One hundred and seventy-eight（29.7%) composite endpoint events were recorded during the follow-up, 19（3.2%) patients died, and 12（2.0%) patients were lost to follow-up. There were 286(47.7%) cases in low NT-proBNP group and 314 cases（52.3%) in high NT-proBNP group. Patients were older, prevalence of atrial fibrillation and myocardial infarction was higher; MMSE scores and ADL scores, albumin and creatinine clearance rate were lower in high NT-proBNP group than in low NT-proBNP group（all P<0.05). At 1-year follow-up, the incidence of composite endpoint events was significantly higher in high NT-proBNP group than in low NT-proBNP group（33.4%（105/314) vs. 24.8%（71/286), P = 0.02). Cardiovascular events were more common in high NT-proBNP group than in low NT-proBNP group（17.5%（55/314) vs. 8.4%（24/286), P = 0.001). Kaplan-Meier survival analysis showed both composite endpoint events（Log-rank P=0.016) and cardiovascular events（Log-rank P=0.001) were higher in high NT-proBNP group than in low NT-proBNP group. All-cause mortality was also significantly higher in highNT-proBNP group than in lowNT-proBNP group（4.8%（15/314) vs. 1.4%（4/286), P = 0.020), and Kaplan-Meier survival analysis demonstrated borderline statistical significance（Log-rank P = 0.052). Cox proportional hazard regression analysis showed that after adjusting for age, sex, creatinine clearance rate, myocardial infarction, and atrial fibrillation, NT-proBNP remained as an independent risk factor for composite endpoint events（HR=1.376，95%CI 1.049-1.806, P=0.021), and cardiovascular events（HR=1.777, 95%CI 1.185-2.664, P=0.005), but not for all-cause mortality（P=0.206). Conclusions: NT-proBNP level at admission has important predictive value on rehospitalization and cardiovascular events for hospitalized elderly non-heart failure patients. NT-proBNP examination is helpful for risk stratification in this patient cohort.
Aged ; Aged, 80 and over ; Biomarkers ; Heart Failure ; Humans ; Male ; Natriuretic Peptide, Brain ; Peptide Fragments ; Prognosis ; Stroke Volume ; Ventricular Function, Left

OBJECTIVE： To analyze the characteristics of adverse drug reactions/events （ADR/ADE） caused by TCM injections in 18 third grade class A hospitals from Xi’an， and to provide reference for rational drug use in clinic. METHODS： Totally 304 ADR/ADE cases of TCM injection reported by 18 third grade class A hospitals of Xi’an were analyzed statistically during 2013-2018 in respect of gender and ages， time distribution of ADR/ADE， distribution of ADR/ADE-inducing drugs， organs/systems involved in ADR/ADE and clinical manifestations， grading of ADR/ADE， outcome and relationship evaluation， drug combination. RESULTS： Totally 6 683 cases of ADR/ADE cases were reported in same period， 304 cases were caused by TCM injection （4.55％）. Among 304 cases of ADR/ADE， the number of women （162 cases， 53.29％） was slightly higher than that of men （142 cases， 46.71％）. The age of patients was mainly over 40 years old （223 cases， 73.35％）. Among them， 118 cases （38.82％） were over 60 years old. ADR/ADE occurred within 1 min to 10 days after administration， especially within 30 min after administration （123 cases， 40.46％）. ADR/ADE involved 36 varieties， mainly including agent for promoting blood circulation and dredging， agent for reinforcing and tonifying and agent for clearing away heat and detoxification， and Danhong injection accounted for the highest proportion （43 cases， 14.14％）. A total of 352 ADR/ADE case times occurred in 304 patients， mainly lesion of skin and appendents （164 case times， 46.59％）， followed by cardiovascular system lesions （54 case times， 15.34％） and systemic lesions （51 case times， 14.49％）. The main clinical manifestations were mainly pruritus （117 case times）， followed by rash （68 case times） and palpitation （34 case times）. Among 304 ADR/ADE reports， 26 cases （8.55％） were severe， 8 cases （2.63％） were new ADR/ADE， 302 cases （99.34％） were cured or improved， 2 cases （0.66％） were unknown， but none of them died. 266 cases （87.50％） were evaluated as likely to be related. 46 patients （15.13％） had combined use of drugs， including 9 cases of combined use of TCM injection and 37 cases of combined use of chemical medicine injection. CONCLUSIONS： TCM injections had a high incidence of ADR/ADE due to the complexity of their components， individual differences and clinical use. Most of them were rapid-onset ADR/ADE within 30 min and mild ADR/ADE commonly seen in lesion of skin and its appendents. The incidence could be reduced by rational clinical use and drug monitoring. For cardiovascular diseases and other basic diseases， attention should be paid to distinguishing their primary diseases from ADR/ADE caused by TCM injections， and more attention should be paid to their individualized drug use.

BACKGROUNDPulmonary hypertension (PH) frequently complicates the course of idiopathic pulmonary fibrosis (IPF) patients and is associated with significantly worse outcomes. The aim of the present study was to investigate the incidence of PH in IPF patients and evaluate the correlation between clinical parameters and systolic pulmonary artery pressure (sPAP).

METHODSHospitalized patients with IPF, who were evaluated for sPAP by Doppler echocardiography from January 2004 to December 2011, were enrolled in our study. Patients were defined as PH by an estimated sPAP > 50 mmHg and graded as PH likely, PH possible and PH unlikely, based on the 2009 European Society of Cardiology/European Respiratory Society PH Guidelines. The correlations between clinical parameters and sPAP were analyzed by multiple linear regression.

RESULTSTotally, 119 IPF patients were enrolled in our study and 28 (23.5%), 20 (16.8%) and 71 (59.7%) patients were PH likely, PH possible and PH unlikely, respectively. Borg dyspnea score was positively correlated with sPAP, r = 0.467, P < 0.001. Oxygen saturation was negatively correlated with sPAP, r = -0.416, P < 0.001. Diffusing capacity of the lung for carbon monoxide percentage predicted was negatively correlated with sPAP, r = -0.424, P = 0.003. N-terminal fragment of pro-brain natriuretic peptide and pulmonary artery width was positively correlated with sPAP, r = 0.452, P = 0.011 and r = 0.513, P < 0.001, respectively.

CONCLUSIONSThe incidence of PH in IPF patients was 23.5% in a single center of China. PH may worsen the dyspnea, right heart dysfunction and decrease the life quality of the patients with IPF.

Aged ; Echocardiography, Doppler ; Female ; Humans ; Hypertension, Pulmonary ; blood ; epidemiology ; physiopathology ; Idiopathic Pulmonary Fibrosis ; blood ; epidemiology ; physiopathology ; Incidence ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Pulmonary Artery ; physiopathology ; Smoking

Objective To investigate the emotional memory impairment in patients with primary insomnia (PI) and explore the neurobiological mechanisms underlying primary insomnia through emotional memory tasks involving different valance of emotional pictures.Methods Thirty patients with primary insomnia(PI group) and twenty healthy controls(HC group) were given emotional memory tasks using positive,neutral and negative valence images.The emotional memory was evaluated by the recognition of emotional pictures.Results Compared with healthy controls (positive (11.60±4.00) , neutral (11.05± 3.73) and negative (12.60± 2.06) , respectively), patients with PI (positive (11.30±3.75),neutral (11.47±3.21) and negative (11.43±4.12) ,respectively) showed no significant difference in appraisal of the emotional pictures (P＞0.05).Compared with healthy controls (43.40± 4.88) for the emotional images memorizing task,patients with PI (39.40±6.43) exhibited evident deficit of all emotional images (P＜0.05).Furthermore, the accuracy in recognizing both positive (12.60± 2.42) and neutral (12.87±3.18) valence pictures were significantly lower in patients with P1 than those in healthy controls(positive (14.05±2.19) and neutral (14.75± 1.80)) (P＜0.05).There was no significant difference in negative stimulus between PI group(13.93±1.76) and HC group(14.70±1.59) (P＞0.05).Conclusion The results suggest thant emotional memory is impaired in patients with PI.Moreover,the emotional memory for positive and neutral vanlence pictures is impaired but the emotional memory for negative is relatively spared in patients with primary insomnia.The results also indicate that impaired emotional memory with different valences may relate with distinct neuromechanisms.

Through collecting and collating the development process of traditional Chinese medicine dispensing, the development of modern Chinese medicine dispensing on the basis of experience could be promoted. "Heyaofenji", "Hehe", " Heji" in ancient Chinese medicine, herbal medicine literature and law were collected, and then things were sorted out according to traditional Chinese medicine dispensing theory, skills and legal norms. Firstly, "Tang Ye Jing Fa" is the earliest book which marks the rudiment of traditional Chinese medicine dispensing. Secondly, traditional Chinese medicine dispensing theory formed in "Shen Nong's herbal classic". Thirdly, Zhang Zhongjing's "Treatise on Febrile Diseases" marked the formation of Chinese medicine dispensing skills. Lastly, Provisions in Tang Dynasty law marks the development of traditional Chinese medicine dispensing.
Chemistry, Pharmaceutical ; education ; history ; legislation & jurisprudence ; methods ; China ; Dosage Forms ; Drug Compounding ; history ; methods ; Drug and Narcotic Control ; history ; legislation & jurisprudence ; Drugs, Chinese Herbal ; chemistry ; History, Ancient ; Medicine in Literature ; Medicine, Chinese Traditional ; history ; methods