ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

The famous classical formulae are epitomes of the clinical practice experience created by doctors in history， as an important symbol of traditional Chinese medicine （TCM） theory and clinical treatment approaches， it has been given a new concept connotation and become one of the breakthroughs for the development of TCM in the new era. Due to the limitations of historical literature and different cognitive perspectives of literature research， there are still common problems in determination of the dosage， original materials， processing and decocting method for the famous classical formulae， which hinder its development and registration process. In the history of more than 2 000 years， famous classical formulae have been developed in the continuous clinical application of practice. This paper systematically reviewed the evolution of the concept and history of the famous classical formulae， and introduced the evolution of the famous classical formulae in terms of name， composition， medicine， dosage， decocting method and clinical functions， including the stability of basic prescription composition， differentiation of drug bases， the progress of processing methods， the characteristics of dosages in different historical periods and the expansion of functions. In view of the research of the key information for famous classical formulae， the paper puts forward the suggestion of paying more attention to the evolution of prescriptions in the past dynasties. In textual research， we should combine the changes of medicinal resources， habits of drug use and production technology of the past dynasties， so as to bridge the ancient and modern. As to the dosage selection， we should be based on the weights and measures of all dynasties and current clinical practice to select rational dosage and decocting method. On the basis of inheriting the essence， follows the ancient but not be bounded by it， and solves the common problems in the textual research of key information from the perspective of history and development.

Objective Circular RNAs (circRNAs) are non-coding RNAs (ncRNA) circularized without a 3' polyadenylation [poly-(A)] tail or a 5' cap, resulting in a covalently closed loop structure. circRNAs were first discovered in RNA viruses in the 1970s, but only a small number of circRNAs were discovered at that time due to limitations in traditional polyadenylated transcriptome analyses. With the development of specific biochemical and computational methods, recent studies have shown the presence of abundant circRNAs in eukaryotic transcriptomes. circRNAs play vital roles in many physiological and pathological processes, such as acting as miRNA sponges, binding to RNA-binding proteins (RBPs), acting as transcriptional regulatory factors, and even serving as translation templates. Current evidence has shown that circRNAs can be potentially used as excellent biomarkers for diagnosis, therapeutic effect evaluation, and prognostic assessment of a variety of diseases, and they may also provide effective therapeutic targets due to their stability and tissue and development-stage specificity. This review focuses on the properties of circRNAs and their immune relationship to disease, and explores the role of circRNAs in immune-related diseases and the directions of future research.
Biomarkers ; MicroRNAs/genetics* ; RNA, Circular ; Transcriptome

Objective     To analyze predictive factors, clinical implications and prognosis effects of new-onset conduction block after transcatheter aortic valve implantation (TAVI). Methods     The clinical data of 86 patients who underwent TAVI through transfemoral approach from 2019 to 2021 in Fujian Provincial Hospital were retrospectively analyzed, including 59 males and 27 females with an average age of 72.9±8.0 years. The patients were divided into a normal group and a new-onset conduction block group according to whether there was new-onset conduction block after operation, and then the new-onset conduction block group was subdivided into a left bundle branch block (LBBB) group (28 patients) and a complete atrioventricular block (CAVB) group (11 patients). We compared the hemodynamics and TAVI-related complications between the postoperative and early follow-up periods, and used the multivariate logistic regression models to identify risk factors for the new-onset conduction block. Results     The median EuroSCORE of all patients were 8 (2) points before the operation. In the postoperative and early follow-up periods, the hemodynamics and TAVI-related complications had no statistical difference between the new-onset conduction block group and the normal group (P>0.05). The incidence of permanent pacemaker implantation (81.8%, 9/11) and mortality due to cardiac causes (18.1%, 2/11) in the CAVB group were significantly higher than those in the normal group and theLBBB group (P<0.05). Female, severe calcification of the aortic valve, too large valve size and deep valve implants were the risk factors for new-onset conduction block after TAVI. Conclusion    The incidence of LBBB and CAVB is high after TAVI, however, both of them do not significantly effect the hemodynamics of the patients. Higher incidence of permanent pacemaker implantation is found in the CAVB group which affects the rate of rehospitalization and mortality. Female patients, severe calcification of the aortic valve, too large valve size and deep valve implants are the risk factors for the new-onset conduction block after TAVI.

Objective: To observe the relationship between impaired myocardial untwisting and left ventricular diastolic dysfunction in patients with autoimmune diseases (AD). Methods: In this retrospective study, 95 AD patients (27 males, (38.6±14.2) years old) were enrolled as AD group and 71 gender and age matched healthy subjects (24 males, (37.6±12.2) years old) were enrolled as control group, all underwent transthoracic echocardiography and two-dimensional speckle-tracking echocardiography (STE) in our hospital between January 2014 and June 2018. Left ventricular untwisting and diastolic function parameters were measured. Multiple logistic regression analysis was used to identify related factors of left ventricular diastolic dysfunction in AD patients. Receiver operating characteristic (ROC) curve was used to identify the diagnosis value of untwisting parameters for left ventricular diastolic dysfunction in AD patients. Results: Compared with control group, left ventricular ejection fraction was lower (58(47, 66)% vs. 67 (62, 71) %, P<0.001), E/e′ was higher (10.78 (7.28, 13.65) vs. 6.30 (5.55, 7.25) , P<0.001), isovolumic relaxation time was longer (73.5 (56.5, 88.0) ms vs. 62.0 (58.0, 68.5) ms, P<0.001),and untwist slope during isovolumic relaxation period (USIR) was lower (31.92 (14.09, 54.92) °/s vs. 59.90 (40.09, 87.18) °/s, P<0.001) in AD group than in control group. Multiple logistic regression analysis showed heart rate (OR=0.885, 95%CI 0.840-0.931, P<0.001), E/e′ (OR=0.655, 95%CI 0.537-0.798, P<0.001) and USIR (OR=0.986, 95%CI 0.974-0.998, P=0.020) were independently related with left ventricular diastolic dysfunction in AD patients. ROC curve showed that area under the curve (AUC) was 0.919 (P<0.001), sensitivity was 87.6%, and specificity was 88.7%, when combining the heart rate, E/e′, and USIR as assessment parameters for the diagnosis of left ventricular diastolic dysfunction in AD patients at a cutoff of 0.51. Conclusions Impairment of myocardial untwisting indicates the presence of early stage left ventricular diastolic dysfunction in AD patients. USIR may be a sensitive parameter to evaluate early stage left ventricular diastolic dysfunction in AD patients.

Purpose To compare the characteristics of targeted ultrasound contrast agents of ovarian carcinoma xenograft tumor at different stages with SonoVue serving as the contract, and to explore the application value of targeted ultrasound contrast agents in diagnosis of ovarian carcinoma. Materials and Methods Fifty BALB/cNude nude mice were randomly divided into 5 groups with 10 in each group to establish subcutaneous xenograft tumor model of ovarian carcinoma. According to different inoculation time (14, 21, 28, 35, 42 d), 5 groups of nude mice underwent common contrast-enhanced ultrasound (MBc) and targeted ultrasound contrast (MBt) examination. The peak intensity (PI) and time to peak (TTP) of xenograft tumors were calculated by time-signal intensity curves, and their angiographic features were dynamically observed. Results PI in MBt group was higher than that in MBc group at different times, the difference of which was all statistically significant (P<0.05); TTP was shorter than that of MBc group, the difference between 14, 21 and 28 d was statistically significant (P<0.05); TIC curve was steeper at the early stage of inoculation. The difference between PI and TTP in MBt group was statistically significant (P<0.05). The difference of PI between 14 and 21 d, 21 and 28 d, 28 and 35 d were all statistically significant (P<0.01); differences of TTP between 14 and 21 d, 28 and 35 d were all statistically significant (P<0.01); the difference of PI and TTP compared within MBc group had no statistical significance (P>0.05). Conclusion In the early stage of inoculation, the contrast parameters PI and TTP carrying MMP-2 antibody-targeted ultrasound contrast agents are more advantageous than sonovue, which is helpful for the early diagnosis of ovarian carcinoma.

Objective To construct a rating scale on the knowledge,attitude,and practice of geriatrics for 8-year clinical medical students and undergraduate nursing students,and to test the reliability and validity of the scale.Methods The Knowledge,Attitude,Practice(KAP)theory was used as a guided framework,relative literatures were reviewed,and topics for question answering were discussed by experts group.Then,a questionnaire was initially constructed.Five methods,including discrete trend method,Cronbach coefficient,t-test,correlation analysis,and factor analysis,were used to screen the attitude and practice items.The knowledge items were evaluated by experts.Items with over three exclusion criteria were deleted when combining the literal questions.The construct validity of the integrated scale was assessed by factor analysis.A pilot research was conducted by 100 eight-year medical students and nursing undergraduates selecting question entries,and the reliability and validity of the scale were examined.Results The scale consisted of three dimensions.A 43-item initiate questionnaire on the scale included 13 items for knowledge,11 for attitude,and 19 for practice.Two knowledge items were deleted according to expert evaluation.Seven items with more than three exclusion criteria were deleted after statistical analyses.Eventually,34 items were included in the questionnaire.The Cronbach α coefficient of the questionnaire was 0.702.And three common factors were extracted according to exploratory factor analysis.Conclusions The reliability and validity of Geriatrics Knowledge,Attitude and Practice scale for eight year medical students and nursing undergraduates are acceptable,but the knowledge items should be recomposed.

Objective To understand the status of knowledge, attitude and practice (KAP) about stroke among the residents in a community of Wenzhou, and to clarify the characteristics of the intervention population and the key points for intervention, so as to carry out health education and health promotion, and improve the prevention and treatment of stroke. Methods An investigation was conducted in a total of 658 residents in a community of Wenzhou, aged from 18 to 90. The content of the investigating included the general information, the KAP about stroke, the identification of stroke warning information and the behavior of seeking medical advice. Results The highest and lowest rate of the knowledge about stroke prevention and treatment was 88.68% and 33.54%; the highest and lowest rate of the correct attitude was 79.75% and 32.67%; and the highest and lowest rate of the correct behavior was 56.17% and 10.89%. The differences of KAP in populations with different characteristics were statistically significant (P< 0.01). The top three stroke warning symptoms were one side of the face or limb numbness or weakness (59.57%), consciousness disturbance (59.42%) and comprehension disturbance (59.12%). The thop three emergency seeking hospital service behaviors of stroke were immediate delivery to hospital (19.60%), continued observation (18.54%) and calling ambulance (18.24%). Conclusions The status quo of community residents' KAP of stroke in Wenzhou is at a low level. It is suggested to carry out targeted health education to improve the residents' knowledge of stroke and promote the change of attitude and behavior, so as to prevent or delay the incidence of stroke.

Objective To study the influence of the minimal invasive Nuss procedure on the pulmonary function of post-operative pectus excavatum patients. Methods Conduct retrospective analysis on the data from 676 pectus excavatum patients who were treated by the minimal invasive Nuss procedure from August 2006 to November 2014. Wherein 182 cases have com-plete preoperative and postoperative pulmonary-function data of one year, three years. These cases were divided into 3 groups according to the age, namely, children group( from 6 to 12 years old, 34 cases) , adolescents group( from 13 to 18 years old, 80 cases) , adults group( above 18 years old, 68 cases) , among which there were 71 cases with pulmonary function data of 1 year after removal of steel plate, they were divided into 3 groups in the same way,namely, children group(20 cases), adoles-cents group(22 cases), adults group(29 cases) . To compare and analyze the pulmonary function indicatrix of patients with dif-ferent ages in preoperative stage, 1 year, 3 years postoperative stages and 1 year after dismantling the steel plate stage, and to investigate the influence of the minimal invasive Nuss procedure on the postoperative lung function. Results The pulmonary function indicatrix in preoperative stage, 1 year, 3 years postoperative stages of the children group did not have significant difference(P>0. 05); the FVC, FEV1 indicatrix of adolescents and adults groups declined after operation in 1 year and 3 years compared with the preoperative stage(P<0. 05), FEF 25％ -75％, FEF 50％, FEF75％ were improved after operation in 1 year and 3 years compared with the preoperative stage(P<0. 05);the pulmonary function indicatrix of three age groups in the 1 year after dismantling the steel plate stage had all improved, in which the pulmonary function indicatrix of the children group improves most significantly(P<0. 05). Conclusion After the minimal invasive Nuss procedure before the plate dis-mantling process, the pulmonary function of children patients remains to be similar. Partial ventilatory function was damaged in the adolescents and adults patients. After the plate dismantling process, the pulmonary function indicatrix of each age group hasimproved in different degrees. Improvement effect is the most significant in patients below the age of 12.